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Mechanical property evaluation of porous 13-93 Bioactive Glass and GL1550 Borate Glass 3D scaffolds in either mechanical or biologic properties. Borate bioactive-glass (BBG) is a promising material for scaffolds due to its higher solubility compared to traditional 13-93 bioactive glass. The main objective
Zhou, Yaoqi
Here we fabricate and characterize bioactive composite scaffolds for bone tissue engineering applications. 45S5 Bioglass«Ā(45S5) or strontium-substituted bioactive glass (SrBG) were incorporated into polycaprolactone (PCL) and fabricated into 3D bioactive composite scaffolds utilizing additive manufacturing technology. We show that composite scaffolds (PCL/45S5 and PCL/SrBG) can be reproducibly manufactured with a scaffold morphology highly resembling that of PCL scaffolds. Additionally, micro-CT analysis reveals BG particles were homogeneously distributed throughout the scaffolds. Mechanical data suggested that PCL/45S5 and PCL/SrBG composite scaffolds have higher compressive Young's modulus compared to PCL scaffolds at similar porosity (?75%). After 1Āday in accelerated degradation conditions using 5M NaOH, PCL/SrBG, PCL/45S5 and PCL lost 48.6 ▒ 3.8%, 12.1 ▒ 1% and 1.6 ▒ 1% of the original mass, respectively. In vitro studies were conducted using MC3T3 cells under normal and osteogenic conditions. All scaffolds were shown to be non-cytotoxic, and supported cell attachment and proliferation. Our results also indicate that the inclusion of bioactive glass (BG) promotes precipitation of calcium phosphate on the scaffold surfaces which leads to earlier cell differentiation and matrix mineralization when compared to PCL scaffolds. However, as indicated by alkaline phosphatase activity, no significant difference in osteoblast differentiation was found between PCL/45S5 and PCL/SrBG scaffolds. These results suggest that PCL/45S5 and PCL/SrBG composite scaffolds show potential as next generation bone scaffolds. PMID:24192136
Poh, Patrina S P; Hutmacher, Dietmar W; Stevens, Molly M; Woodruff, Maria A
In vitro bioactivity and cytocompatibility of porous scaffolds of bioactive borosilicate glasses
The bioactive borosilicate scaffolds (R2O-RO-B2O3-SiO2-P2O5) with four different contents of borate were fabricated by replication technique. The bioactivity, degradability and the\\u000a cytotoxicity of the scaffolds were studied in this paper. The porosity of the scaffolds was found to be 73%¢80%, and the pore\\u000a size was in the range of 200¢300 ?m. The porous scaffolds immersed in 0.02 molĘL?1 K2HPO4 solution
Xin Zhang; HaiLuo Fu; Xin Liu; AiHua Yao; DePing Wang; WenHai Huang; Ying Zhao; XinQuan Jiang
In this study, we fabricated strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds with controlled architecture and enhanced mechanical strength using a three-dimensional (3-D) printing technique. The study showed that Sr-MBG scaffolds had uniform interconnected macropores and high porosity, and their compressive strength was ?170 times that of polyurethane foam templated MBG scaffolds. The physicochemical and biological properties of Sr-MBG scaffolds were evaluated by ion dissolution, apatite-forming ability and proliferation, alkaline phosphatase activity, osteogenic expression and extracelluar matrix mineralization of osteoblast-like cells MC3T3-E1. The results showed that Sr-MBG scaffolds exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment with increasing Sr substitution. Importantly, Sr-MBG scaffolds possessed good apatite-forming ability, and stimulated osteoblast cells' proliferation and differentiation. Using dexamethasone as a model drug, Sr-MBG scaffolds also showed a sustained drug delivery property for use in local drug delivery therapy, due to their mesoporous structure. Therefore, the 3-D printed Sr-MBG scaffolds combined the advantages of Sr-MBG such as good bone-forming bioactivity, controlled ion release and drug delivery and enhanced mechanical strength, and had potential application in bone regeneration. PMID:24412143
Zhang, Jianhua; Zhao, Shichang; Zhu, Yufang; Huang, Yinjun; Zhu, Min; Tao, Cuilian; Zhang, Changqing
Three-dimensional, bioactive, biodegradable, polymerbioactive glass composite scaffolds with
-BA composite was found to be a bioactive material, as it formed surface calcium phosphate deposits in a simu of PLAGA-BG were measured, and the formation of a surface calcium phosphate layer was evaluated by sur
Lu, Helen H.
Bioactive glass-based composites for the production of dense sintered bodies and porous scaffolds.
Recently several attempts have been made to combine calcium phosphates, such as ?-tricalcium phosphate (?-TCP) and, most of all, hydroxyapatite (HA), with bioactive glasses of different composition, in order to develop composites with improved biological and mechanical performance. Unfortunately, the production of such systems usually implies a high-temperature treatment (up to 1300 ░C), which may result in several drawbacks, including crystallization of the original glass, decomposition of the calcium phosphate phase and/or reactions between the constituent phases, with non-trivial consequences in terms of microstructure, bioactivity and mechanical properties of the final samples. In the present contribution, novel binary composites have been obtained by sintering a bioactive glass, characterized by a low tendency to crystallize, with the addition of HA or ?-TCP as the second phase. In particular, the composites have been treated at a relatively low temperature (818 ░C and 830 ░C, depending on the sample), thus preserving the amorphous structure of the glass and minimizing the interaction between the constituent phases. The effects of the glass composition, calcium phosphate nature and processing conditions on the composite microstructure, mechanical properties and in vitro bioactivity have been systematically discussed. To conclude, a feasibility study to obtain scaffolds for bone tissue regeneration has been proposed. PMID:23498242
Bellucci, D; Sola, A; Cannillo, V
An important objective in bone tissue engineering is to fabricate biomimetic three-dimensional scaffolds that stimulate mineralization for rapid regeneration of bone. In this work, scaffolds of electrospun poly(vinyl alcohol) (PVA) fibers (diameter = 286 ▒ 14 nm) were coated with a sol-gel derived bioactive glass (BG) and evaluated in vitro for potential applications in bone repair. Structural and chemical analyses showed that the BG coating was homogeneously deposited on the PVA fibers. In vitro cell culture studies showed that the BG-coated PVA scaffold had a greater capacity to support proliferation of osteogenic MC3T3-E1 cells, alkaline phosphatase activity, and mineralization than the uncoated PVA scaffold. The BG coating improved the tensile strength of the PVA scaffold from 18 ▒ 2 MPa to 21 ▒ 2 MPa, but reduced the elongation to failure from 94 ▒ 4% to 64 ▒ 5%. However, immersion of the BG-coated PVA scaffolds in a simulated body fluid for 5 days resulted in an increase in the tensile strength (24 ▒ 2 MPa) and elongation to failure (159 ▒ 4%). Together, the results show that these BG-coated PVA scaffolds could be considered as candidate materials for bone tissue engineering applications. PMID:22374712
Gao, Chunxia; Gao, Qiang; Li, Yadong; Rahaman, Mohamed N; Teramoto, Akira; Abe, Koji
Polycaprolactone (PCL) is a resorbable polymer used extensively in bone tissue engineering owing to good structural properties and processability. Strontium-substituted bioactive glass (SrBG) has the ability to promote osteogenesis and may be incorporated into scaffolds intended for bone repair. Here, we describe for the first time, the development of a PCL-SrBG composite scaffold incorporating 10% (weight) of SrBG particles into PCL bulk, produced by the technique of melt electrospinning. We show that we are able to reproducibly manufacture composite scaffolds with an interconnected porous structure and, furthermore, these scaffolds were demonstrated to be noncytotoxic in vitro. Ions present in the SrBG component were shown to dissolve into cell culture media and promoted precipitation of a calcium phosphate layer on the scaffold surface which in turn led to noticeably enhanced alkaline phosphatase activity in MC3T3-E1 cells compared to PLC-only scaffolds. These results suggest that melt-electrospun PCL-SrBG composite scaffolds show potential to become effective bone graft substitutes. PMID:24133006
Ren, Jiongyu; Blackwood, Keith A; Doustgani, Amir; Poh, Patrina P; Steck, Roland; Stevens, Molly M; Woodruff, Maria A
A new composition of gelatin/bioactive-glass/silver nanoparticle was synthesized and employed to prepare antibacterial macroporous scaffolds with potential applications in bone tissue engineering. A set of macroporous nanocomposite scaffolds were developed from an aqueous solution of gelatin by freeze-drying and crosslinking using genipin at ambient temperature. Silver nanoparticles were successfully synthesized in situ in gelatin solution by heat treatment reduction as a simple and "green" method in which gelatin acted as a natural reducing and stabilizing agent. The effect of the incorporation of the bioactive-glass and the silver nanoparticle concentration on the physicochemical properties of the scaffolds, such as the gel fraction, porosity, in vitro enzyme degradation, morphology, and swelling behavior was studied. Furthermore, the in vitro viability of human mesenchymal stem cells (hMSC) and the antibacterial activity against gram-negative Escherichia coli and gram-positive Staphylococcus aureus were tested on the scaffolds. It was found that upon the addition of silver nanoparticles the porosity, pore size, swelling, and antibacterial properties were enhanced. The silver nanoparticles increased the in vitro enzyme degradation in samples without bioactive-glass; however, the degradation was remarkably reduced by addition of bioactive-glass. In addition, formation of apatite particles, the main inorganic constituent of the bone, on the surface of the bioactive-glass containing scaffolds were confirmed after immersion in simulated body fluid (SBF). The viability of hMSC on the scaffold suggested that gelatin/bioactive-glass/nanosilver scaffolds can be used as an antibacterial scaffolds. PMID:24749388
Yazdimamaghani, M; Vashaee, D; Assefa, S; Walker, K J; Madihally, S V; K÷hler, G A; Tayebi, L
Graphene is a novel material and currently popular as an enabler for the next-generation nanocomposites. Here, we report the use of graphene to improve the mechanical properties of nano-58S bioactive glass for bone repair and regeneration. And the composite scaffolds were fabricated by a homemade selective laser sintering system. Qualitative and quantitative analysis demonstrated the successful incorporation of graphene into the scaffold without obvious structural damage and weight loss. The optimum compressive strength and fracture toughness reached 48.65 ▒ 3.19?MPa and 1.94 ▒ 0.10?MPaĘm1/2 with graphene content of 0.5?wt%, indicating significant improvements by 105% and 38% respectively. The mechanisms of pull-out, crack bridging, crack deflection and crack tip shielding were found to be responsible for the mechanical enhancement. Simulated body fluid and cell culture tests indicated favorable bioactivity and biocompatibility of the composite scaffold. The results suggest a great potential of graphene/nano-58S composite scaffold for bone tissue engineering applications. PMID:24736662
Gao, Chengde; Liu, Tingting; Shuai, Cijun; Peng, Shuping
There is a need for synthetic bone graft substitutes to repair large bone defects resulting from trauma, malignancy, and congenital diseases. Bioactive glass has attractive properties as a scaffold material but factors that influence its ability to regenerate bone in vivo are not well understood. In the present work, the ability of strong porous scaffolds of 13¢93 bioactive glass with an oriented microstructure to regenerate bone was evaluated in vivo using a rat calvarial defect model. Scaffolds with an oriented microstructure of columnar pores (porosity = 50%; pore diameter = 50¢150 Ąm) showed mostly osteoconductive bone regeneration, and new bone formation, normalized to the available pore area (volume) of the scaffolds, increased from 37% at 12 weeks to 55% at 24 weeks. Scaffolds of the same glass with a trabecular microstructure (porosity = 80%; pore width = 100¢500 Ąm), used as the positive control, showed bone regeneration in the pores of 25% and 46% at 12 and 24 weeks, respectively. The brittle mechanical response of the as-fabricated scaffolds changed markedly to an elasto-plastic response in vivo at both implantation times. These results indicate that both groups of 13¢93 bioactive glass scaffolds could potentially be used to repair large bone defects, but scaffolds with the oriented microstructure could also be considered for the repair of loaded bone. PMID:22922251
Liu, Xin; Rahaman, Mohamed N.; Fu, Qiang
The pro-angiogenic properties of multi-functional bioactive glass composite scaffolds.
The angiogenic properties of micron-sized (m-BG) and nano-sized (n-BG) bioactive glass (BG) filled poly(D,L lactide) (PDLLA) composites were investigated. On the basis of cell culture work investigating the secretion of vascular endothelial growth factor (VEGF) by human fibroblasts in contact with composite films (0, 5, 10, 20 wt %), porous 3D composite scaffolds, optimised with respect to the BG filler content capable of inducing angiogenic response, were produced. The in vivo vascularisation of the scaffolds was studied in a rat animal model and quantified using stereological analyses. The prepared scaffolds had high porosities (81-93%), permeability (k = 5.4-8.6 x 10?? m▓) and compressive strength values (0.4-1.6 MPa) all in the range of trabecular bone. On composite films containing 20 wt % m-BG or n-BG, human fibroblasts produced 5 times higher VEGF than on pure PDLLA films. After 8 weeks of implantation, m-BG and n-BG containing scaffolds were well-infiltrated with newly formed tissue and demonstrated higher vascularisation and percentage blood vessel to tissue (11.6-15.1%) than PDLLA scaffolds (8.5%). This work thus shows potential for the regeneration of hard-soft tissue defects and increased bone formation arising from enhanced vascularisation of the construct. PMID:21411138
Gerhardt, Lutz-Christian; Widdows, Kate L; Erol, Melek M; Burch, Charles W; Sanz-Herrera, Josķ A; Ochoa, Ignacio; Stõmpfli, Rolf; Roqan, Iman S; Gabe, Simon; Ansari, Tahera; Boccaccini, Aldo R
PHBV microsphere/45S5 bioactive glass (BG) composite scaffolds with drug release function were developed for bone tissue engineering. BG-based glass-ceramic scaffolds with high porosity (94%) and interconnected pore structure prepared by foam replication method were coated with PHBV microspheres (nominal diameter=3.5 ?m) produced by water-in-oil-in-water double emulsion solvent evaporation method. A homogeneous microsphere coating throughout the porous structure of scaffolds was obtained by a simple dip coating method, using the slurry of PHBV microspheres in hexane. Compressive strength tests showed that the microsphere coating slightly improved the mechanical properties of the scaffolds. It was confirmed that the microsphere coating did not inhibit the bioactivity of the scaffolds in SBF. Hydroxyapatite crystals homogeneously grew not only on the struts of the scaffolds but also on the surface of microspheres within 7 days of immersion in SBF. Vancomycin was successfully encapsulated into the PHBV microspheres. The encapsulated vancomycin was released with a dual release profile involving a relatively low initial burst release (21%) and a sustained release (1 month), which is favorable compared to the high initial burst release (77%) and short release period (4 days) measured on uncoated scaffolds. The developed bioactive composite scaffold with drug delivery function has thus the potential to be used advantageously in bone tissue engineering. PMID:24907766
Li, Wei; Ding, Yaping; Rai, Ranjana; Roether, Judith A; Schubert, Dirk W; Boccaccini, Aldo R
Micro PIXE-RBS for the study of Sr release at bioactive glass scaffolds/biological medium interface
NASA Astrophysics Data System (ADS)
Strontium is a very interesting element in bone regeneration as it can promote bone formation and limit bone resorption. Bone tissue engineering has a very high potential as a method for bone healing and it requires a 3D macroporous scaffold to serve as a support for cell growth. In that purpose, strontium containing bioactive glass foams made with the sol-gel foaming process are very promising scaffolds as they combine the high bioactivity of bioactive glasses, the beneficial effects of strontium on bone growth and a structure that would allow cell adhesion, cell invasion and vascularization. This paper reports the synthesis of such a material and its in vitro bioactivity study. The release of strontium ions from the material to the biological medium occurs quickly, as shown by ICP-AES results, with the delivery of quantities of Sr ions that should be adequate for bone regeneration. Ion microbeam techniques evidence a very specific behavior of strontium: it is rapidly removed from the inner part of the material but remains in the calcium phosphate layer that is deposited on the surface of the foam pores. It reveals the particular behavior of glass foams compared to other materials suitable for implantation like glass powders of same composition and highlights the interest of ion microbeam techniques in the study of strontium-containing bioactive glass scaffolds.
Lacroix, Josķphine; Lao, Jonathan; Nedelec, Jean-Marie; Jallot, Edouard
The development of inorganic-organic hybrid scaffolds with controllable degradation and bioactive properties is receiving considerable interest for bone and tissue regeneration. The objective of this study was to create hybrid scaffolds of gelatin and bioactive glass (BG) with a controlled, three-dimensional (3D) architecture by a combined sol-gel and robotic deposition (robocasting) method and evaluate their mechanical response, bioactivity, and response to cells in vitro. Inks for robotic deposition of the scaffolds were prepared by dissolving gelatin in a sol-gel precursor solution of the bioactive glass (70SiO2 -25CaO-5P2 O5 ; mol%) and aging the solution to form a gel with the requisite viscosity. After drying and crosslinking, the gelatin-BG scaffolds, with a grid-like architecture (filament diameter ?350 Ąm; pore width ?550 Ąm), showed an elasto-plastic response, with a compressive strength of 5.1 ▒ 0.6 MPa, in the range of values for human trabecular bone (2-12 MPa). When immersed in phosphate-buffered saline, the crosslinked scaffolds rapidly absorbed water (?440% of its dry weight after 2 h) and showed an elastic response at deformations up to ?60%. Immersion of the scaffolds in a simulated body fluid resulted in the formation of a hydroxyapatite-like surface layer within 5 days, indicating their bioactivity in vitro. The scaffolds supported the proliferation, alkaline phosphatase activity, and mineralization of osteogenic MC3T3-E1 cells in vitro, showing their biocompatibility. Altogether, the results indicate that these gelatin-BG hybrid scaffolds with a controlled, 3D architecture of inter-connected pores have potential for use as implants for bone regeneration. PMID:23255226
Gao, Chunxia; Rahaman, Mohamed N; Gao, Qiang; Teramoto, Akira; Abe, Koji
Boron is one of the trace elements in the human body which plays an important role in bone growth. Porous mesopore bioactive glass (MBG) scaffolds are proposed as potential bone regeneration materials due to their excellent bioactivity and drug-delivery ability. The aims of the present study were to develop boron-containing MBG (B-MBG) scaffolds by sol-gel method and to evaluate the effect of boron on the physiochemistry of B-MBG scaffolds and the response of osteoblasts to these scaffolds. Furthermore, the effect of dexamethasone (DEX) delivery in B-MBG scaffold system was investigated on the proliferation, differentiation and bone-related gene expression of osteoblasts. The composition, microstructure and mesopore properties (specific surface area, nano-pore volume and nano-pore distribution) of B-MBG scaffolds have been characterized. The effect of boron contents and large-pore porosity on the loading and release of DEX in B-MBG scaffolds were also investigated. The results have shown that the incorporation of boron into MBG scaffolds slightly decreases the specific surface area and pore volume, but maintains well-ordered mesopore structure and high surface area and nano-pore volume compared to non-mesopore bioactive glass. Boron contents in MBG scaffolds did not influence the nano-pore size distribution or the loading and release of DEX. B-MBG scaffolds have the ability to maintain a sustained release of DEX in a long-term span. Incorporating boron into MBG glass scaffolds led to a controllable release of boron ions and significantly improved the proliferation and bone-related gene expression (Col I and Runx2) of osteoblasts. Furthermore, the sustained release of DEX from B-MBG scaffolds significantly enhanced alkaline phosphatase (ALP) activity and gene expressions (Col I, Runx2, ALP and BSP) of osteoblasts. These results suggest that boron plays an important role in enhancing osteoblast proliferation in B-MBG scaffold system and DEX-loaded B-MBG scaffolds show great potential as a release system to enhance osteogenic property for bone tissue engineering application. PMID:21704367
Wu, Chengtie; Miron, Richard; Sculean, Anton; Kaskel, Stefan; Doert, Thomas; Schulze, Renate; Zhang, Yufeng
Bioactive glasses are biocompatible materials that convert to hydroxyapatite in vivo, and potentially support bone formation, but have mainly been available in particulate and not scaffold form. In this study, borosilicate and borate bioactive glass scaffolds were evaluated in critical-sized rat calvarial defects. Twelve-week-old rats were implanted with 45S5 silicate glass particles and scaffolds of 1393 silicate, 1393B1 borosilicate, and 1393B3 borate glass. After 12 weeks, the defects were harvested, stained with hematoxylin and eosin to evaluate bone regeneration, Periodic Acid Schiff to quantitate blood vessel area, and von Kossa and backscatter SEM to estimate newly mineralized bone and hydroxyapatite conversion of bioactive glasses. The amount of new bone was 12.4% for 45S5, 8.5% for 1393, 9.7% for 1393B1, and 14.9% for 1393B3 (*p = 0.04; cf. 1393 and 1393B1). Blood vessel area was significantly higher (p = 0.009) with 45S5 (3.8%), with no differences among 1393 (2.0%), 1393B1 (2.4%), or 1393B3 (2.2%). Percent von Kossa-positive area was 18.7% for 45S5, 25.4% for 1393, 29.5% for 1393B1, and 30.1% for 1393B3, significantly higher (p = 0.014) in 1393B1 and 1393B3 glasses than in 45S5. 45S5 and 1393B3 converted completely to HA in vivo. The 1393B3 glass provided greater bone formation and may be more promising for bone defect repair due to its capacity to be molded into scaffolds. ® 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:3267-3275, 2012. PMID:22733586
Bi, Lianxiang; Jung, Steve; Day, Delbert; Neidig, Katie; Dusevich, Vladimir; Eick, David; Bonewald, Lynda
In this study, 3D porous bioactive composite scaffolds were produced and evaluated for their physico-chemical and biological properties. Polymer poly-L-lactide-co-glycolide (PLGA) matrix scaffolds were modified with sol-gel-derived bioactive glasses (SBGs) of CaO-SiO2-P2O5 systems. We hypothesized that SBG incorporation into PLGA matrix would improve the chemical and biological activity of composite materials as well as their mechanical properties. We applied two bioactive glasses, designated as S2 or A2, differing in the content of SiO2 and CaO (i.e. 80?mol% SiO2, 16?mol% CaO for S2 and 40?mol% SiO2, 52?mol% CaO for A2). The composites were characterized for their porosity, bioactivity, microstructure and mechanical properties. The osteoinductive properties of these composites were evaluated in human bone marrow stromal cell (hBMSC) cultures grown in either standard growth medium or treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) or dexamethasone (Dex). After incubation in simulated body fluid, calcium phosphate precipitates formed inside the pores of both A2-PLGA and S2-PLGA scaffolds. The compressive strength of the latter was increased slightly compared to PLGA. Both composites promoted superior hBMSC attachment to the material surface and stimulated the expression of several osteogenic markers in hBMSC compared to cells grown on unmodified PLGA. There were also marked differences in the response of hBMSC to composite scaffolds, depending on chemical compositions of the scaffolds and culture treatments. Compared to silica-rich S2-PLGA, hBMSC grown on calcium-rich A2-PLGA were overall less responsive to rhBMP-2 or Dex and the osteoinductive properties of these A2-PLGA scaffolds seemed partially dependent on their ability to induce BMP signaling in untreated hBMSC. Thus, beyond the ability of currently studied composites to enhance hBMSC osteogenesis, it may become possible to modulate the osteogenic response of hBMSC, depending on the chemistry of SBGs incorporated into polymer matrix. PMID:25329328
Filipowska, J; Pawlik, J; Cholewa-Kowalska, K; Tylko, G; Pamula, E; Niedzwiedzki, L; Szuta, M; Laczka, M; Osyczka, A M
Evaluation of 3D nano¢macro porous bioactive glass scaffold for hard tissue engineering
Recently, nano¢macro dual-porous, three-dimensional (3D) glass structures were developed for use as bioscaffolds for hard\\u000a tissue regeneration, but there have been concerns regarding the interconnectivity and homogeneity of nanopores in the scaffolds,\\u000a as well as the cytotoxicity of the environment deep inside due to limited fluid access. Therefore, mercury porosimetry, nitrogen\\u000a absorption, and TEM have been used to characterize nanopore
S. Wang; M. M. Falk; A. Rashad; M. M. Saad; A. C. Marques; R. M. Almeida; M. K. Marei; H. Jain
Alveolar bone loss and bone defects are the commonly encountered periodontal problems. Large defects do not heal spontaneously and thus require surgical interventions with bone substitutes. Bone grafts have the disadvantages of eliciting an immunologic response with subsequent graft rejection. The success rate of Guided Tissue Regeneration (GTR) is variable because of high susceptibility to infection. Thus emerged the important role of synthetic biomaterials and hence for this purpose we developed a nanocomposite scaffold, using alpha- and beta-chitin hydrogel with bioactive glass ceramic nanoparticles (nBGC) and silver nanoparticles (nAg) by lyophilization technique (aalpha and beta-chitin hydrogel/nBGC/nAg nanocomposite scaffold). The prepared nanoparticles and nanocomposite scaffolds were characterized. In addition, the porosity, swelling, mechanical properties, antibacterial activity, in vitro degradation and biomineralization, cell viability, cell attachment and cell proliferation ability of the prepared composite scaffolds were also evaluated. The results showed that alpha- and beta-chitin/nBGC/nAg composite scaffolds were porous and have the capacity to absorb fluids and swell. The composite scaffolds also showed enhanced antibacterial activity, bioactivity and controlled degradation in comparison to the control scaffolds. Cell viability studies proved the non-toxic nature of the nanocomposite scaffolds. Cell attachment and cell proliferation studies revealed the attachment and spreading nature of cells. All these studies revealed that, these antibacterial nanocomposite scaffolds could be a promising approach for the management of periodontal defects. PMID:24059080
Srinivasan, Sowmya; Kumar, P T Sudheesh; Nair, Sreeja V; Nair, Shantikumar V; Chennazhi, K P; Jayakumar, R
Composite scaffolds of mesoporous bioactive glass and polyamide for bone repair
A bone-implanted porous scaffold of mesoporous bioglass/polyamide composite (m-BPC) was fabricated, and its biological properties were investigated. The results indicate that the m-BPC scaffold contained open and interconnected macropores ranging 400¢500 ?m, and exhibited a porosity of 76%. The attachment ratio of MG-63 cells on m-BPC was higher than polyamide scaffolds at 4 hours, and the cells with normal phenotype extended well when cultured with m-BPC and polyamide scaffolds. When the m-BPC scaffolds were implanted into bone defects of rabbit thighbone, histological evaluation confirmed that the m-BPC scaffolds exhibited excellent biocompatibility and osteoconductivity, and more effective osteogenesis than the polyamide scaffolds in vivo. The results indicate that the m-BPC scaffolds improved the efficiency of new bone regeneration and, thus, have clinical potential for bone repair. PMID:22679367
Su, Jiacan; Cao, Liehu; Yu, Baoqing; Song, Shaojun; Liu, Xinwei; Wang, Zhiwei; Li, Ming
Hybrid foam (BG-PVA) with 50 % Bioactive glass (BG) and 50 % polyvinyl alcohol (PVA) was prepared by sol-gel process to produce scaffolds for bone tissue engineering. The pore structure of hydrated foams was evaluated by 3-D confocal microscopy, confirming 70% porosity and interconnected macroporous network. In this study, we assessed the putative advantage of coating with osteostatin pentapeptide into BG-PVA hybrid scaffolds to improve their bioactivity. In vitro cell culture experiments were performed using mouse pre-osteoblastic MC3T3-E1 cell line. The exposure to osteostatin loaded-BG-PVA scaffolds increase cell proliferation in contrast with the unloaded scaffolds. An in vivo study was selected to implant BG-PVA scaffolds, non-coated (Group A) or coated (Group B) with osteostatin into non critical bone defect at rabbit femur. Both groups showed new compact bone formation on implant surface, with lamellae disposed around a haversian canal forming osteons-like structure. We observed signs of inflammation around the implanted unloaded scaffold at one month, but resolved at 3 months. This early inflammation did not occur in Group B; supporting the notion that osteostatin may act as anti-inflammatory inhibitor. On the other hand, Group B showed increased bone formation, as depicted by many new trabeculae partly mineralized in the implant regenerating area, incipient at 1 month and more evident at 3 months after implantation. PVA/BG hybrid scaffolds present a porous structure suitable to support osteoblast proliferation and differentiation. Our in vitro and in vivo findings indicate that osteostatin coating improves the osteogenic features of these scaffolds. PMID:24772196
Coletta, D J; Lozano, D; Rocha-Oliveira, A A; Mortarino, P; Bumaguin, G E; Vitelli, E; Vena, R; Missana, L; Jammal, M V; Portal-N·±ez, S; Pereira, M; Esbrit, P; Feldman, S
In this work, the role of shock wave-induced increase of bone morphogenetic proteins in modulating the osteogenic properties of osteoblast-like cells seeded on a bioactive scaffold was investigated using gremlin as a bone morphogenetic protein antagonist. Bone-like glass-ceramic scaffolds, based on a silicate experimental bioactive glass developed at the Politecnico di Torino, were produced by the sponge replication method and used as porous substrates for cell culture. Human MG-63 cells, exposed to shock waves and seeded on the scaffolds, were treated with gremlin every two days and analysed after 20 days for the expression of osteoblast differentiation markers. Shock waves have been shown to induce osteogenic activity mediated by increased expression of alkaline phosphatase, osteocalcin, type I collagen, BMP-4 and BMP-7. Cells exposed to shock waves plus gremlin showed increased growth in comparison with cells treated with shock waves alone and, conversely, mRNA contents of alkaline phosphatase and osteocalcin were significantly lower. Therefore, the shock wave-mediated increased expression of bone morphogenetic protein in MG-63 cells seeded on the scaffolds is essential in improving osteogenic activity; blocking bone morphogenetic protein via gremlin completely prevents the increase of alkaline phosphatase and osteocalcin. The results confirmed that the combination of glass-ceramic scaffolds and shock waves exposure could be used to significantly improve osteogenesis opening new perspectives for bone regenerative medicine. PMID:24994880
Muzio, Giuliana; Martinasso, Germana; Baino, Francesco; Frairia, Roberto; Vitale-Brovarone, Chiara; Canuto, Rosa A
NASA Technical Reports Server (NTRS)
Paul Ducheyne, a principal investigator in the microgravity materials science program and head of the University of Pernsylvania's Center for Bioactive Materials and Tissue Engineering, is leading the trio as they use simulated microgravity to determine the optimal characteristics of tiny glass particles for growing bone tissue. The result could make possible a much broader range of synthetic bone-grafting applications. Bioactive glass particles (left) with a microporous surface (right) are widely accepted as a synthetic material for periodontal procedures. Using the particles to grow three-dimensional tissue cultures may one day result in developing an improved, more rugged bone tissue that may be used to correct skeletal disorders and bone defects. The work is sponsored by NASA's Office of Biological and Physical Research.
Preparation of bioactive porous HA/PCL composite scaffolds
NASA Astrophysics Data System (ADS)
Porous hydroxyapatite (HA) bioceramic scaffold has been widely attracted the attention to act as a three-dimensional (3D) template for cell adhesion, proliferation, differentiation and thus promoting bone and cartilage regeneration because of its osteoinduction. However, the porous bioceramic scaffold is fragile so that it is not suitable to be applied in clinic for bone repair or replacement. Therefore, it is significant to improve the mechanical property of porous HA bioceramics while the interconnected structure is maintained for tissue ingrowth in vivo. In the present research, a porous composite scaffold composed of HA scaffold and polycaprolactone (PCL) lining was fabricated by the method of polymer impregnating to produce HA scaffold coated with PCL lining. Subsequently, the composite scaffolds were deposited with biomimetic coating for improving the bioactivity. The HA/PCL composite scaffolds with improved mechanical property and bioactivity is expected to be a promising bone substitute in tissue engineering applications.
Zhao, J.; Guo, L. Y.; Yang, X. B.; Weng, J.
Bioactive glass nanoparticles with negative zeta potential
The purpose of this work was to produce and characterize SiO2¢CaO¢P2O5 bioactive glass nanoparticles with negative zeta potential for possible use in biomedical applications. 63S bioactive glass was obtained using the sol¢gel method. X-ray fluorescence (XRF) spectroscopy and dispersive X-ray analysis (EDX) confirmed the preparation of the 63S bioactive glass with 62.17% SiO2, 28.47% CaO and 9.25% P2O5 (in molar
Ali Doostmohammadi; Ahmad Monshi; Rasoul Salehi; Mohammad Hossein Fathi; Zahra Golniya; Alma. U. Daniels
Sol-gel-derived bioactive glass containing SiO2-MgO-CaO-P2O5 as an antibacterial scaffold.
Bioactive glass (BG) composites with a base of SiO2-Na2O-CaO-P2O5 are biocompatible biomaterials. The assessment of their abilities for medical applications has interested researchers. We produced a BG-containing SiO2-MgO-CaO-P2O5 by the sol-gel method. To determine the antibacterial effects, we analyzed the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) properties of this product on three microorganisms, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, known causative agents for biofilm formation on implant surfaces. In addition, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to study the cytotoxic effects of our composite on animal cells. Our results demonstrated that our BG product inhibited the growth of bacteria in a concentration-dependent manner without any cytotoxic effects. Therefore, our BG product can be utilized as an appropriate implant for treating bone and tooth defects. PMID:23138930
Fooladi, Abbas Ali Imani; Hosseini, Hamideh Mahmoodzadeh; Hafezi, Forough; Hosseinnejad, Fatemeh; Nourani, Mohammad Reza
Optimization and characterization of bioactive glass nanofibers and nanocomposites
NASA Astrophysics Data System (ADS)
Disease affects different areas of the bone and can impact individuals of all pathologies and ethnicities. These bone diseases can result in weakening which leads to trauma during ordinary function, the need for reconstructive surgery, and eventual bone replacement. Tissue engineering can provide a less traumatic and more fundamental solution to the current therapies. Bioactive glasses are promising materials in tissue engineering applications because of their ability to form hydroxycarbonate apatite in the presence of simulated body fluid, support cell adhesion, growth, and differentiation, induce bone formation, and concentrate bone morphogenic proteins in vivo. The research in this dissertation will attempt to improve the quality, yield, and toughness of bioactive glass nanofibrous scaffolds. The three specific aims of this research include, (1) Optimization and Characterization of Surfactant Modified Bioactive Glass (2) Optimization of Direct Synthesis Bioactive glass Nanofibers from Sols (3) Mechanical Properties and In-vitro Biomineralization of Bioglass-loaded Polyglyconate Nanocomposites Created Using the Particulate Leaching Method. The purpose of the first specific aim was to optimize the processing of bioactive glass nanofibers, resulting in greater fiber uniformity with a reduction in beading. The increase in viscosity coupled with the ability of the surfactant to limit polymeric secondary bonding led to improved fiber quality. The focal point of the second specific aim is the production of sol-gel derived glass fibers with high bioactivity prepared by electrospinning without the use of any polymer carrier system. Advantages of this method include decreased processing time, increased production of fibers, and a decrease in the loss of material due to the calcining process. The solvent cast/ particulate leaching method was used to create a nanocomposite of bioglass and the co-polymer polyglyconate (MaxonRTM) for bone tissue scaffolds The biocompatibility of the composite foams was observed and calcium phosphate presence was quantified. The incorporation of bioglass into the polymer matrix improved the strength (modulus - 21.47 MPa) and biocompatibility of the polyglyconate foam. Keywords: Bioactive glass, Electrospinning, Solvent Casting/Particulate Leaching Method, Nanocomposites
Scarber, Reginna E.
A well-defined mesoporous structure of wollastonite with high specific surface area was synthesized using surfactant P123 (triblock copolymer) as template, and its composite scaffolds with poly(epsilon-caprolactone) (PCL) were fabricated by a simple method of solvent casting-particulate leaching. The measurements of the water contact angles suggest that the incorporation of either mesoporous wollastonite (m-WS) or conventional wollastonite (c-WS) into PCL could improve the hydrophilicity of the composites, and the former was more effective than the later. The bioactivity of the composite scaffold was evaluated by soaking the scaffolds in a simulated body fluid (SBF) and the results show that the m-WS/PCL composite (m-WPC) scaffolds can induce a dense and continuous layer of apatite after soaking for 1 week, as compared with the scattered and discrete apatite particles on the c-WS/PCL composite (c-WPC) scaffolds. The m-WPC had a significantly enhanced apatite-forming bioactivity compared with the c-WPC owing to the high specific surface area and pore volume of m-WS. In addition, attachment and proliferation of MG(63) cells on m-WPC scaffolds were significantly higher than that of c-WPC, revealing that m-WPC scaffolds had excellent biocompatibility. Such improved properties of m-WPC should be helpful for developing new biomaterials and may have potential use in hard tissue repair. PMID:19019424
Wei, Jie; Chen, Fangping; Shin, Jung-Woog; Hong, Hua; Dai, Chenglong; Su, Jiancan; Liu, Changsheng
Organised nanoporous SBA-15 type silica precursor (SP) particulate material has been processed into three-dimensional macroporous, reticulated structures using a novel strategy consisting of blending increasing percentages of SP with a SiO2 -CaO-P2 O5 (80Si15Ca5P) mesoporous bioactive glass (MBG) sol. The procedure successfully produced consolidated and functionally competent open-cell scaffolds while preserving the nanoporous order of the SP. Scaffolds were prepared using four different (MBG)/(SP) ratios. These structures were then characterized using field emission gun scanning electron microscopy, X-ray diffraction (XRD), nitrogen adsorption-desorption measurements, and compressive strength testing. Open-cell interconnected structures with dual macro (150-500 ?m) and nano (4-6 nm)-organised porosity were produced. Both the textural and mechanical properties were found to improve with increasing SBA-15 content. The in vitro bioactive response using simulated body fluid confirmed high reactivity for all prepared scaffolds. In addition, the SBA-15 containing scaffolds exhibited a superior ability to delay the pH-triggered lysozyme release with antibiotic activity. PMID:24123840
Ramiro-Gutiķrrez, M Lourdes; Will, Julia; Boccaccini, Aldo R; DĒaz-Cuenca, Arßnzazu
Bioactive glass coatings for orthopedic metallic implants
The objective of this work is to develop bioactive glass coatings for metallic orthopedic implants. A new family of glasses in the SiO2-Na2O-K2O-CaO-MgO-P2O5 system has been synthesized and characterized. The glass properties (thermal expansion, softening and transformation temperatures, density and hardness) are in line with the predictions of established empirical models. The optimized firing conditions to fabricate coatings on Ti-based and Co-Cr alloys have been determined and related to the glass properties and the interfacial reactions. Excellent adhesion to alloys has been achieved through the formation of 100-200 nm thick interfacial layers (Ti5Si3 on Ti-based alloys and CrOx on Co-Cr). Finally, glass coatings, approximately 100 mu m thick, have been fabricated onto commercial Ti alloy-based dental implants.
Lopez-Esteban, Sonia; Saiz, Eduardo; Fujino, Sigheru; Oku, Takeo; Suganuma, Katsuaki; Tomsia, Antoni P.
Borate bioactive glasses are biocompatible and enhance new bone formation, but the effect of their microstructure on bone regeneration has received little attention. In this study scaffolds of borate bioactive glass (1393B3) with three different microstructures (trabecular, fibrous, and oriented) were compared for their capacity to regenerate bone in a rat calvarial defect model. 12weeks post-implantation the amount of new bone, mineralization, and blood vessel area in the scaffolds were evaluated using histomorphometric analysis and scanning electron microscopy. The amount of new bone formed was 33%, 23%, and 15%, respectively, of the total defect area for the trabecular, oriented, and fibrous microstructures. In comparison, the percent new bone formed in implants composed of silicate 45S5 bioactive glass particles (250-300?m) was 19%. Doping the borate glass with copper (0.4 wt.% CuO) had little effect on bone regeneration in the trabecular and oriented scaffolds, but significantly enhanced bone regeneration in the fibrous scaffolds (from 15 to 33%). The scaffolds were completely converted to hydroxyapatite within the 12week implantation. The amount of hydroxyapatite formed, 22%, 35%, and 48%, respectively, for the trabecular, oriented, and fibrous scaffolds, increased with increasing volume fraction of glass in the as-fabricated scaffold. Blood vessels infiltrated into all the scaffolds, but the trabecular scaffolds had a higher average blood vessel area compared with the oriented and fibrous scaffolds. While all three scaffold microstructures were effective in supporting bone regeneration, the trabecular scaffolds supported more bone formation and may be more promising in bone repair. PMID:23643606
Bi, Lianxiang; Rahaman, Mohamed N; Day, Delbert E; Brown, Zackary; Samujh, Christopher; Liu, Xin; Mohammadkhah, Ali; Dusevich, Vladimir; Eick, J David; Bonewald, Lynda F
A review of bioactive glasses: Their structure, properties, fabrication, and apatite formation.
Bioactive glass and glass-ceramics are used in bone repair applications and are being developed for tissue engineering applications. Bioactive glasses/bioglass are very attractive materials for producing scaffolds devoted to bone regeneration due to their versatile properties, which can be properly designed depending on their composition. An important feature of bioactive glasses, which enables them to work for applications in bone tissue engineering, is their ability to enhance revascularization, osteoblast adhesion, enzyme activity and differentiation of mesenchymal stem cells as well as osteoprogenitor cells. An extensive amount of research work has been carried out to develop silicate, borate/borosilicate bioactive glasses and phosphate glasses. Along with this, some metallic glasses have also been investigated for biomedical and technological applications in tissue engineering. Many trace elements have also been incorporated in the glass network to obtain the desired properties, which have beneficial effects on bone remodeling and/or associated angiogenesis. The motivation of this review is to provide an overview of the general requirements, composition, structure-property relationship with hydroxyapatite formation and future perspectives of bioglasses. Attention has also been given to developments of metallic glasses and doped bioglasses along with the techniques used for their fabrication. ® 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013. PMID:23468256
Kaur, Gurbinder; Pandey, Om P; Singh, Kulvir; Homa, Dan; Scott, Brian; Pickrell, Gary
Biomimetic and bioactive nanofibrous scaffolds from electrospun composite nanofibers
Electrospinning is an enabling technology that can architecturally (in terms of geometry, morphology or topography) and biochemically fabricate engineered cellular scaffolds that mimic the native extracellular matrix (ECM). This is especially important and forms one of the essential paradigms in the area of tissue engineering. While biomimesis of the physical dimensions of native ECMÆs major constituents (eg, collagen) is no longer a fabrication-related challenge in tissue engineering research, conveying bioactivity to electrospun nanofibrous structures will determine the efficiency of utilizing electrospun nanofibers for regenerating biologically functional tissues. This can certainly be achieved through developing composite nanofibers. This article gives a brief overview on the current development and application status of employing electrospun composite nanofibers for constructing biomimetic and bioactive tissue scaffolds. Considering that composites consist of at least two material components and phases, this review details three different configurations of nanofibrous composite structures by using hybridizing basic binary material systems as example. These are components blended composite nanofiber, core-shell structured composite nanofiber, and nanofibrous mingled structure. PMID:18203429
Zhang, YZ; Su, B; Venugopal, J; Ramakrishna, S; Lim, CT
The quest for synthetic materials to repair load-bearing bone lost because of trauma, cancer, or congenital bone defects requires development of porous and high-performance scaffolds with exceptional mechanical strength. However, the low mechanical strength of porous bioactive ceramic and glass scaffolds, compared with that of human cortical bone, has limited their use for these applications. In the present work, bioactive 6P53B glass scaffolds with superior mechanical strength were fabricated using a direct ink writing technique. The rheological properties of Pluronic« F-127 (referred to hereafter simply as F-127) hydrogel-based inkswere optimized for the printing of features as fine as 30 ?m and of the three-dimensional scaffolds. The mechanical strength and in vitro degradation of the scaffolds were assessed in a simulated body fluid (SBF). The sintered glass scaffolds show a compressive strength (136 ▒ 22 MPa) comparable to that of human cortical bone (100-150 MPa), while the porosity (60%) is in the range of that of trabecular bone (50-90%).The strength is ~100 times that of polymer scaffolds and 4¢5 times that of ceramic and glass scaffolds with comparable porosities. Despite the strength decrease resulting from weight loss during immersion in an SBF, the value (77 MPa) is still far above that of trabecular bone after three weeks. The ability to create both porous and strong structures opens a new avenue for fabricating scaffolds for load-bearing bone defect repair and regeneration. PMID:21745606
Fu, Qiang; Saiz, Eduardo; Tomsia, Antoni P.
The impact of bone diseases and trauma in the whole world has increased significantly in the past decades. Bioactive glasses are regarded as an important bone regeneration material owing to their generally excellent osteoconductivity and osteostimulativity. A new class of bioactive glass, referred to as mesoporous bioglass (MBG), was developed 7 years ago, which possess a highly ordered mesoporous channel structure and a highly specific surface area. The study of MBG for drug/growth factor delivery and bone tissue engineering has grown significantly in the past several years. In this article, we review the recent advances of MBG materials, including the preparation of different forms of MBG, composition¢structure relationship, efficient drug/growth factor delivery and bone tissue engineering application. By summarizing our recent research, the interaction of MBG scaffolds with bone-forming cells, the effect of drug/growth factor delivery on proliferation and differentiation of tissue cells and the in vivo osteogenesis of MBG scaffolds are highlighted. The advantages and limitations of MBG for drug delivery and bone tissue engineering have been compared with microsize bioactive glasses and nanosize bioactive glasses. The future perspective of MBG is discussed for bone regeneration application by combining drug delivery with bone tissue engineering and investigating the in vivo osteogenesis mechanism in large animal models. PMID:23741607
Wu, Chengtie; Chang, Jiang
Efficient discovery of bioactive scaffolds by activity-directed synthesis.
The structures and biological activities of natural products have often provided inspiration in drug discovery. The functional benefits of natural products to the host organism steers the evolution of their biosynthetic pathways. Here, we describe a discovery approach-which we term activity-directed synthesis-in which reactions with alternative outcomes are steered towards functional products. Arrays of catalysed reactions of ?-diazo amides, whose outcome was critically dependent on the specific conditions used, were performed. The products were assayed at increasingly low concentration, with the results informing the design of a subsequent reaction array. Finally, promising reactions were scaled up and, after purification, submicromolar ligands based on two scaffolds with no previous annotated activity against the androgen receptor were discovered. The approach enables the discovery, in tandem, of both bioactive small molecules and associated synthetic routes, analogous to the evolution of biosynthetic pathways to yield natural products. PMID:25242481
Karageorgis, George; Warriner, Stuart; Nelson, Adam
Efficient discovery of bioactive scaffolds by activity-directed synthesis
NASA Astrophysics Data System (ADS)
The structures and biological activities of natural products have often provided inspiration in drug discovery. The functional benefits of natural products to the host organism steers the evolution of their biosynthetic pathways. Here, we describe a discovery approachŚwhich we term activity-directed synthesisŚin which reactions with alternative outcomes are steered towards functional products. Arrays of catalysed reactions of ?-diazo amides, whose outcome was critically dependent on the specific conditions used, were performed. The products were assayed at increasingly low concentration, with the results informing the design of a subsequent reaction array. Finally, promising reactions were scaled up and, after purification, submicromolar ligands based on two scaffolds with no previous annotated activity against the androgen receptor were discovered. The approach enables the discovery, in tandem, of both bioactive small molecules and associated synthetic routes, analogous to the evolution of biosynthetic pathways to yield natural products.
Karageorgis, George; Warriner, Stuart; Nelson, Adam
Submicron bioactive glass tubes for bone tissue engineering
Herein we describe a method to fabricate submicron bioactive glass tubes using sol¢gel and coaxial electrospinning techniques for applications in bone tissue engineering. Heavy mineral oil and gel solution were delivered by two independent syringe pumps during the coaxial electrospinning process. Subsequently, submicron bioactive glass tubes were obtained by removal of poly(vinyl pyrrolidone) and heavy mineral oil via calcination at
Jingwei Xie; Eric R. Blough; Chi-Hwa Wang
Mineralization and osteoblast response to bioactive glass in vitro.
Bioactive glass, an osteoproductive material, has received considerable attention as a bone graft substitute in the treatment of bony defects. Bioactive CaO-SiO(2)-P(2)O(5) glass was prepared using the sol-gel method, and mineralization behaviour in vitro was investigated by soaking it in simulated body fluid (SBF). Cellular cultivation in vitro, MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) and Von Kossa assays were conducted to evaluate the osteoblast response to the bioactive glass. A calcium phosphate carbonate hydroxide (HCA) layer was formed on the bioactive glass after soaking for 3 days in SBF, which indicated that the mineralization on the surface of bioactive glass could progress spontaneously. The osteoblast response results demonstrated that bioactive glass had no cytotoxicity, and it might not be harmful to the morphology of the osteoblast. The growth and proliferation of the osteoblastic cell could not be inhibited. Nodule formation was also observed in conditioned medium containing dissolution bioactive glass and these nodules were shown to be mineralized by Von Kossa staining, which indicates that bioactive glass shows good biocompatibility. PMID:20397850
Zhou, Z H; Yi, Q F; Nei, H D; Ling, Y L; Zhou, J N; Liu, L H; Liu, X P
Biodegradable and bioactive porous scaffold structures prepared using fused deposition modeling.
Three-dimensional printing (3DP) refers to a group of additive manufacturing techniques that can be utilized in tissue engineering applications. Fused deposition modeling (FDM) is a 3DP method capable of using common thermoplastic polymers. However, the scope of materials applicable for FDM has not been fully recognized. The purpose of this study was to examine the creation of biodegradable porous scaffold structures using different materials in FDM and to determine the compressive properties and the fibroblast cell response of the structures. To the best of our knowledge, the printability of a poly(?-caprolactone)/bioactive glass (PCL/BAG) composite and L-lactide/?-caprolactone 75/25 mol % copolymer (PLC) was demonstrated for the first time. Scanning electron microscope (SEM) images showed BAG particles at the surface of the printed PCL/BAG scaffolds. Compressive testing showed the possibility of altering the compressive stiffness of a scaffold without changing the compressive modulus. Compressive properties were significantly dependent on porosity level and structural geometry. Fibroblast proliferation was significantly higher in polylactide than in PCL or PCL/BAG composite. Optical microscope images and SEM images showed the viability of the cells, which demonstrated the biocompatibility of the structures. PMID:23281260
Korpela, Jyrki; Kokkari, Anne; Korhonen, Harri; Malin, Minna; Nõrhi, Timo; Seppõlõ, Jukka
Bioactive glasses: Importance of structure and properties in bone regeneration
NASA Astrophysics Data System (ADS)
This review provides a brief background on the applications, mechanisms and genetics involved with use of bioactive glass to stimulate regeneration of bone. The emphasis is on the role of structural changes of the bioactive glasses, in particular Bioglass, which result in controlled release of osteostimulative ions. The review also summarizes the use of Raman spectroscopy, referred to hereto forward as bio-Raman spectroscopy, to obtain rapid, real time in vitro analysis of human cells in contact with bioactive glasses, and the osteostimulative dissolution ions that lead to osteogenesis. The bio-Raman studies support the results obtained from in vivo studies of bioactive glasses, as well as extensive cell and molecular biology studies, and thus offers an innovative means for rapid screening of new bioactive materials while reducing the need for animal testing.
Hench, Larry L.; Roki, Niksa; Fenn, Michael B.
Alkali-free bioactive glasses for bone tissue engineering: A preliminary investigation
An alkali-free series of bioactive glasses has been designed and developed in the glass system CaO-MgO-SiO2-P2O5-CaF2 along diopside (CaMgSi2O6) ¢ fluorapatite [Ca5(PO4)3F] ¢ tricalcium phosphate (3CaOĢP2O5) join. The silicate network in all the investigated glasses is predominantly coordinated in Q2 (Si) units while phosphorus tends to remain in orthophosphate (Q0) environment. The in vitro bioactivity analysis of glasses has been made by immersion of glass powders in simulated body fluid (SBF) while chemical degradation has been studied in Tris-HCl in accordance with ISO-10993-14. Some of the investigated glasses exhibit hydroxyapatite (HA) formation on their surface with in 1-12 h of their immersion in SBF solution. The sintering and crystallization kinetics of glasses has been investigated by differential thermal analysis (DTA) and hot-stage microscopy (HSM), respectively while the crystalline phase evolution in resultant glass-ceramics (GCs) has been studied in the temperature range of 800-900 oC using powder X-ray diffraction (XRD) and scanning electron microscope (SEM). The cell growth and osteogenic differentiation for glasses has been studied in vitro on sintered glass powder compacts using rat bone marrow mesenchymal stem cells. The as designed glasses are ideal candidates for their potential applications in bone tissue engineering in the form of bioactive glasses as well as glass/GC scaffolds.
Goel, Ashutosh; Kapoor, Saurabh; Rajagopal, Raghu R.; Pascual, Maria J.; Kim, Hae-Won; Ferreira, Jose M.
A biomaterial scaffold is one of the key factors for successful tissue engineering. In recent years, an increasing tendency\\u000a has been observed toward the combination of scaffolds and biomolecules, e.g. growth factors and therapeutic genes, to achieve\\u000a bioactive scaffolds, which not only provide physical support but also express biological signals to modulate tissue regeneration.\\u000a Huge efforts have been made on
Wei Ji; Yan Sun; Fang Yang; Jeroen J. J. P. van den Beucken; Mingwen Fan; Zhi Chen; John A. Jansen
The development of suitable bioactive three-dimensional scaffold for the promotion of cellular proliferation and differentiation\\u000a is critical in periodontal tissue engineering. In this study,porous ?-tricalcium phosphate\\/chitosan composite scaffolds were\\u000a prepared through a freeze-drying method. These scaffolds were evaluated by analysis of microscopic structure, porosity, and\\u000a cytocompatibility. The gene expression of bone sialoprotein (BSP) and cementum attachment protein (CAP) was detected
Feng LiaoYangyang ChenZubing Li; Yangyang Chen; Zubing Li; Yining Wang; Bin Shi; Zhongcheng Gong; Xiangrong Cheng
Paper-based bioactive scaffolds for stem cell-mediated bone tissue engineering.
Bioactive, functional scaffolds are required to improve the regenerative potential of stem cells for tissue reconstruction and functional recovery of damaged tissues. Here, we report a paper-based bioactive scaffold platform for stem cell culture and transplantation for bone reconstruction. The paper scaffolds are surface-engineered by an initiated chemical vapor deposition process for serial coating of a water-repellent and cell-adhesive polymer film, which ensures the long-term stability in cell culture medium and induces efficient cell attachment. The prepared paper scaffolds are compatible with general stem cell culture and manipulation techniques. An optimal paper type is found to provide structural, physical, and mechanical cues to enhance the osteogenic differentiation of human adipose-derived stem cells (hADSCs). A bioactive paper scaffold significantly enhances in vivo bone regeneration of hADSCs in a critical-sized calvarial bone defect. Stacking the paper scaffolds with osteogenically differentiated hADSCs and human endothelial cells resulted in vascularized bone formation in vivo. Our study suggests that paper possesses great potential as a bioactive, functional, and cost-effective scaffold platform for stem cell-mediated bone tissue engineering. To the best of our knowledge, this is the first study reporting the feasibility of a paper material for stem cell application to repair tissue defects. PMID:25241158
Park, Hyun-Ji; Yu, Seung Jung; Yang, Kisuk; Jin, Yoonhee; Cho, Ann-Na; Kim, Jin; Lee, Bora; Yang, Hee Seok; Im, Sung Gap; Cho, Seung-Woo
Investigation of bioactivity and cell effects of nano-porous sol-gel derived bioactive glass film
NASA Astrophysics Data System (ADS)
In orthopedic surgery, bioactive glass film coating is extensively studied to improve the synthetic performance of orthopedic implants. A lot of investigations have confirmed that nano-porous structure in bioactive glasses can remarkably improve their bioactivity. Nevertheless, researches on preparation of nano-porous bioactive glasses in the form of film coating and their cell response activities are scarce. Herein, we report the preparation of nano-porous bioactive glass film on commercial glass slide based on a sol-gel technique, together with the evaluation of its in vitro bioactivity through immersion in simulated body fluid and monitoring the precipitation of apatite-like layer. Cell responses of the samples, including attachment, proliferation and osteogenic differentiation, were also investigated using BMSCS (bone marrow derived mesenchymal stem cells) as a model. The results presented here provide some basic information on structural influence of bioactive glass film on the improvement of bioactivity and cellular effects.
Ma, Zhijun; Ji, Huijiao; Hu, Xiaomeng; Teng, Yu; Zhao, Guiyun; Mo, Lijuan; Zhao, Xiaoli; Chen, Weibo; Qiu, Jianrong; Zhang, Ming
Interactions of bioactive glass materials in the oral environment
NASA Astrophysics Data System (ADS)
The aim of this research was to investigate bioactive glass materials for their use in dental restorations. Mechanical properties such as strength, toughness and wear resistance were considered initially, but the focus of this thesis was the biological properties such as reactions with saliva and interactions with natural dental tissues. Bioactive composite materials were created by incorporating bioactive glass and alumina powders into an aqueous suspension, slip casting, and infiltrating with resin. Microstructure, mechanical properties and wear resistance were evaluated. Mechanically, the composites are comparable to natural dental tissues and current dental materials with a strength of 206 +/- 18.7 MPa and a toughness of 1.74 +/- 0.08 MPa(m)1/2. Interfacial reactions were examined using bulk bioactive glasses. Disks were prepared from a melt, placed in saliva and incubated at 37░C. Surfaces were analyzed at 2, 5, 10, 21, and 42 days using scanning electron microscopy (SEM) and microdiffraction. Results showed changes at 2 days with apatite crystallization by 10 days. These glass disks were then secured against extracted human dentin and incubated in saliva for 21 or 42 days. Results from SEM, electron microprobe analysis (EMPA) and microdiffraction showed that dentin and bioactive glasses adhered in this in vitro environment due to attraction of collagen to bioactive glasses and growth of an interfacial apatite. After investigating these bulk glass responses, particulate bioactive glasses were placed in in vitro and in vivo set-ups for evaluation. Particles immersed in biologically buffered saliva showed crystallization of apatite at 3 days. These bioactive glass particles were placed in the molars of mini-pigs and left in vivo. After 30 days the bioactive paste was evaluated using SEM, EMPA and microdiffraction analyses. Results showed that the paste gained structural integrity and had chemical changes in vivo. These sets of experiments show that bioactive glasses have many mechanical and biological characteristics desirable for use in dental materials. Hopefully, the conclusions presented here will lead to further investigations toward their use in dentistry.
Efflandt, Sarah Elizabeth
Background Graphene oxide (GO) is a single layer carbon sheet with a thickness of less than 1 nm. GO has good dispersibility due to surface modifications with numerous functional groups. Reduced graphene oxide (RGO) is produced via the reduction of GO, and has lower dispersibility. We examined the bioactivity of GO and RGO films, and collagen scaffolds coated with GO and RGO. Methods GO and RGO films were fabricated on a culture dish. Some GO films were chemically reduced using either ascorbic acid or sodium hydrosulfite solution, resulting in preparation of RGO films. The biological properties of each film were evaluated by scanning electron microscopy (SEM), atomic force microscopy, calcium adsorption tests, and MC3T3-E1 cell seeding. Subsequently, GO- and RGO-coated collagen scaffolds were prepared and characterized by SEM and compression tests. Each scaffold was implanted into subcutaneous tissue on the backs of rats. Measurements of DNA content and cell ingrowth areas of implanted scaffolds were performed 10 days post-surgery. Results The results show that GO and RGO possess different biological properties. Calcium adsorption and alkaline phosphatase activity were strongly enhanced by RGO, suggesting that RGO is effective for osteogenic differentiation. SEM showed that RGO-modified collagen scaffolds have rough, irregular surfaces. The compressive strengths of GO- and RGO-coated scaffolds were approximately 1.7-fold and 2.7-fold greater, respectively, when compared with the non-coated scaffold. Tissue ingrowth rate was 39% in RGO-coated scaffolds, as compared to 20% in the GO-coated scaffold and 16% in the non-coated scaffold. Conclusion In summary, these results suggest that GO and RGO coatings provide different biological properties to collagen scaffolds, and that RGO-coated scaffolds are more bioactive than GO-coated scaffolds. PMID:25050063
Kanayama, Izumi; Miyaji, Hirofumi; Takita, Hiroko; Nishida, Erika; Tsuji, Maiko; Fugetsu, Bunshi; Sun, Ling; Inoue, Kana; Ibara, Asako; Akasaka, Tsukasa; Sugaya, Tsutomu; Kawanami, Masamitsu
Surface characterization of silver-doped bioactive glass.
A bioactive glass belonging to the system SiO(2)-CaO-Na(2)O was doped with silver ions by ion exchange in molten salts as well as in aqueous solution. The ion exchange in the solution was done to check if it is possible to prepare an antimicrobial material using a low silver content. The doped glass was characterized by means of X-ray diffraction, SEM observation, EDS analysis, bioactivity test (soaking in a simulated body fluid), leaching test (GFAAS analyses) and cytotoxicity test. It is demonstrated that these surface silver-doped glasses maintain, or even improve, the bioactivity of the starting glass. The measured quantity of released silver into simulated body fluid compares those reported in literature for the antibacterial activity and the non-cytotoxic effect of silver. Cytotoxicity tests were carried out to understand the effect of the doped surfaces on osteogenic cell adhesion and proliferation. PMID:15792537
VernĶ, E; Di Nunzio, S; Bosetti, M; Appendino, P; Brovarone, C Vitale; Maina, G; Cannas, M
Bioprinting based on thermal inkjet printing is a promising but unexplored approach in bone tissue engineering. Appropriate cell types and suitable biomaterial scaffolds are two critical factors to generate successful bioprinted tissue. This study was undertaken in order to evaluate bioactive ceramic nanoparticles in stimulating osteogenesis of printed bone marrow-derived human mesenchymal stem cells (hMSCs) in poly(ethylene glycol)dimethacrylate (PEGDMA) scaffold. hMSCs suspended in PEGDMA were co-printed with nanoparticles of bioactive glass (BG) and hydroxyapatite (HA) under simultaneous polymerization so the printed substrates were delivered with highly accurate placement in three-dimensional (3D) locations. hMSCs interacted with HA showed the highest cell viability (86.62 ▒ 6.02%) and increased compressive modulus (358.91 ▒ 48.05 kPa) after 21 days in culture among all groups. Biochemical analysis showed the most collagen production and highest alkaline phosphatase activity in PEG-HA group, which is consistent with gene expression determined by quantitative PCR. Masson's trichrome staining also showed the most collagen deposition in PEG-HA scaffold. Therefore, HA is more effective comparing to BG for hMSCs osteogenesis in bioprinted bone constructs. Combining with our previous experience in vasculature, cartilage, and muscle bioprinting, this technology demonstrates the capacity for both soft and hard tissue engineering with biomimetic structures. PMID:25130390
Gao, Guifang; Schilling, Arndt F; Yonezawa, Tomo; Wang, Jiang; Dai, Guohao; Cui, Xiaofeng
Broad-spectrum bactericidal activity of Ag(2)O-doped bioactive glass.
Bioactive glass has found extensive application as an orthopedic and dental graft material and most recently also as a tissue engineering scaffold. Here we report an initial investigation of the in vitro antibacterial properties of AgBG, a novel bioactive glass composition doped with Ag(2)O. The bacteriostatic and bactericidal properties of this new material and of two other bioactive glass compositions, 45S5 Bioglass and BG, have been studied by using Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus as test microorganisms. Concentrations of AgBG in the range of 0.05 to 0.20 mg of AgBG per ml of culture medium were found to inhibit the growth of these bacteria. Not only was AgBG bacteriostatic, but it also elicited a rapid bactericidal action. A complete bactericidal effect was elicited within the first hours of incubation at AgBG concentrations of 10 mg ml(-1). 45S5 Bioglass and BG had no effect on bacterial growth or viability. The antibacterial action of AgBG is attributed exclusively to the leaching of Ag(+) ions from the glass matrix. Analytical measurements rule out any contribution to AgBG-mediated bacterial killing by changes in pH or ionic strength or the dissolution of other ionic species from the biomaterials. Our observations of the dissolution profiles of Ag(+) from AgBG in the presence and absence of bacteria are consistent with silver accumulation by the bacteria. PMID:12019112
Bellantone, Maria; Williams, Huw D; Hench, Larry L
The magnetic and macro/mesoporous bioactive glasses scaffolds are synthesised successfully by the combination of coral and P123 as co-templates through an evaporation-induced self-assembly process. The prepared material can induce the precipitation of hydroxyapatite layers on their surface in SBF only within 12 h. At the same time, the material exhibited excellent super-paramagnetic and mechanical property. Furthermore, the biocompatible assessment confirmed that the obtained material presented the good biocompatibility and the enhanced adherence of HeLa cells. Herein, the novel materials are expected to have potential application for bone tissue engineering. PMID:25429508
Bian, Chunhui; Lin, Huiming; Zhang, Feng; Ma, Jie; Li, Fengxiao; Wu, Xiaodan; Qu, Fengyu
In the present study, poly(?-caprolactone)-coated hydroxyapatite scaffold derived from cuttlefish bone was prepared. Hydrothermal transformation of aragonitic cuttlefish bone into hydroxyapatite (HAp) was performed at 200░C retaining the cuttlebone architecture. The HAp scaffold was coated with a poly(?-caprolactone) (PCL) using vacuum impregnation technique. The compositional and morphological properties of HAp and PCL-coated HAp scaffolds were studied by means of X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis. Bioactivity was tested by immersion in Hank's balanced salt solution (HBSS) and mechanical tests were performed at compression. The results showed that PCL-coated HAp (HAp/PCL) scaffold resulted in a material with improved mechanical properties that keep the original interconnected porous structure indispensable for tissue growth and vascularization. The compressive strength (0.88MPa) and the elastic modulus (15.5MPa) are within the lower range of properties reported for human trabecular bones. The in vitro mineralization of calcium phosphate (CP) that produces the bone-like apatite was observed on both the pure HAp scaffold and the HAp/PCL composite scaffold. The prepared bioactive scaffold with enhanced mechanical properties is a good candidate for bone tissue engineering applications. PMID:24268280
Milovac, Dajana; Gallego Ferrer, Gloria; Ivankovic, Marica; Ivankovic, Hrvoje
There is a growing interest in the use of calcium phosphate, used to fabricate porous scaffolds for bone tissue regeneration and repair. However, it is difficult to obtain interconnected pores with very high porosity and to engineer the topography of the pore walls for calcium phosphate ceramic scaffolds. In this study, a novelty method interfacial mineralization reaction was used to fabricate porous nano-calcium phosphate ceramic scaffolds with three-dimensional surface topography of walls, which was tuned using different surfactants; using this method, porous scaffolds with different shapes were obtained, which demonstrates that interfacial mineralization reaction is not only a good method to prepare porous ceramic scaffolds of calcium phosphate but also an efficient approach to engineer the topography of the pore walls. The as-prepared porous ceramic scaffolds have also been proved to have good biocompatibility, bioactivity, and biodegradability, which are necessary for the clinical application. In vivo experimental results revealed that not only osteoconduction but also osteoinduction was responsible for the bone formation in our scaffolds, which accelerated the formation of new bone, and that the degradation process of our porous scaffolds could match osteoinduction, mineralization of matrix and bone, and reconstruction of new bone very well, and porous scaffolds could be completely substituted by the new bone. ® 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1749-1761, 2014. PMID:24692259
Wang, Jianxin; Yan, Haoran; Chen, Taijun; Wang, Yingying; Li, Huiyong; Zhi, Wei; Feng, Bo; Weng, Jie; Zhu, Minghua
Application of Evolutionary Game Theory on stem cells interaction in bio-active scaffolds
Cardiac diseases represent one of the biggest death causes in modern society. Current therapies, despite their importance, do not give an efficient solution to the problem. However, stem cells research could represent a future hope for a more efficient solution. In particular, there is currently a great interest in myocardial tissue generation from stem cells cultures in 3D bio-active scaffolds.
A. Boni; C. Stallo; T. Rossi; M. Ruggieri; P. Di Nardo
A novel silver-doped bioactive glass powder (AgBG) was used to coat resorbable Vicryl (polyglactin 910) and non-resorbable Mersilk surgical sutures, thereby imparting bioactive, antimicrobial and bactericidal properties to the sutures. Stable and homogeneous coatings on the surface of the sutures were achieved using an optimised aqueous slurry-dipping technique. Dynamic mechanical analysis (DMA) was used to investigate the viscoelastic parameters of storage modulus and tandelta and thermal transitions of the as-received and composite (coated) sutures. The results generally showed that the bioactive glass coating did not affect the dynamic mechanical and thermal properties of the sutures. The in vitro bioactivity of the sutures was tested by immersion in simulated body fluid (SBF). After only 3 days of immersion in SBF, bonelike hydroxyapatite formed on the coated suture surfaces, indicating their enhanced bioactive behaviour. Resorbable sutures with bioactive coatings as fabricated here, in conjunction with 3-D textile technology, may provide attractive materials for producing 3-D scaffolds with controlled porosities for tissue engineering applications. The bactericidal properties imparted by the Ag-containing glass coating open also new opportunities for use of the composite sutures in wound healing and body wall repair. PMID:14643606
Blaker, J J; Nazhat, S N; Boccaccini, A R
Bioactive glass has been investigated for variety of tissue engineering applications. In this study, fabrication, in vitro and in vivo evaluation of bioactive glass nanocomposite scaffold were investigated. The nanocomposite scaffolds with compositions based on gelatin and bioactive glass nanoparticles were prepared. The apatite formation at the surface of the nanocomposite samples confirmed by Fourier transform infrared spectroscopy, scanning electron microscopy and X-ray powder diffraction analyses. The in vitro characteristics of bioactive glass scaffold as well as the in vivo bone formation capacity of the bioactive glass scaffold in rabbit ulnar model were investigated. The bioactive glass scaffold showed no cytotoxicity effects in vitro. The nanocomposite scaffold made from gelatin and bioactive glass nanoparticles could be deliberated as an extremely bioactive and prospective bone tissue engineering implant. Bioactive glass scaffolds were capable of guiding bone formation in a rabbit ulnar critical-sized-defect model. Radiographic evaluation indicated that successful bridging of the critical-sized defect on the sides both next to and away from the radius took place using bioactive glass scaffolds. X-ray analysis also proposed that bioactive glass scaffolds supported normal bone formation via intramembranous formation. PMID:22826004
Hafezi, Forough; Hosseinnejad, Fatemeh; Fooladi, Abbas Ali Imani; Mafi, Soroush Mohit; Amiri, Afsaneh; Nourani, Mohammad Reza
Mechanical performance of novel bioactive glass containing dental restorative composites
Department of Restorative Dentistry, School of Dentistry, Oregon Health & Science University, Portland, OR, USA AbstractMechanical performance of novel bioactive glass containing dental restorative composites D for remineralization of tooth tissue, and therefore may be a strategic additive for dental restorative materials
Kruzic, Jamie
A review of glass-ionomers: From conventional glass-ionomer to bioactive glass-ionomer
Materials used in the body, especially the materials used in various oral cavity regions should be stable and passive without any interactions with the body tissues or fluids. Dental amalgam, composite resins and dental cements are the materials of choice with such properties. The first attempts to produce active materials, which could interact with the human body tissues and fluids were prompted by the concept that fluoride-releasing materials exert useful effects in the body. The concept of using the ōsmartö materials in dentistry has attracted a lot of attention in recent years. Conventional glass-ionomer (GI) cements have a large number of applications in dentistry. They are biocompatible with the dental pulp to some extent. GI is predominantly used as cements in dentistry; however, they have some disadvantages, the most important of which is lack of adequate strength and toughness. In an attempt to improve the mechanical properties of the conventional GI, resin-modified glass-ionomers have been marketed, with hydrophilic monomers, such as hydroxyethyl methacrylated (HEMA). Some recent studies have evaluated GI with bioactive glass in its structure to validate the claims that such a combination will improve tooth bioactivity, regeneration capacity and restoration. There is ever-increasing interest in the application of bioactive materials in the dental field in an attempt to remineralize affected dentin. The aim of this review article is to evaluate these materials and their characteristics and applications. PMID:24130573
Khoroushi, Maryam; Keshani, Fateme
Current Progress in Bioactive Ceramic Scaffolds for Bone Repair and Regeneration
Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration. PMID:24646912
Gao, Chengde; Deng, Youwen; Feng, Pei; Mao, Zhongzheng; Li, Pengjian; Yang, Bo; Deng, Junjie; Cao, Yiyuan; Shuai, Cijun; Peng, Shuping
Current progress in bioactive ceramic scaffolds for bone repair and regeneration.
Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration. PMID:24646912
Gao, Chengde; Deng, Youwen; Feng, Pei; Mao, Zhongzheng; Li, Pengjian; Yang, Bo; Deng, Junjie; Cao, Yiyuan; Shuai, Cijun; Peng, Shuping
Silver-containing mesoporous bioactive glass with improved antibacterial properties.
The aim of the present work is the study of the bacteriostatic/bactericidal effect of a silver-containing mesoporous bioactive glass obtained by evaporation-induced self-assembly and successive thermal stabilization. Samples of the manufactured mesophase were characterized by means of transmission electron microscopy and N? adsorption/desorption at 77 K, revealing structural and textural properties similar to SBA-15 mesoporous silica. Glass samples used for bioactivity experiments were put in contact with a standardized, commercially available cell culture medium instead of lab-produced simulated body fluid, and were then characterized by means of X-ray diffraction, field emission scanning electron microscopy and Fourier transform infrared spectroscopy. All these analyses confirmed the development of a hydroxyl carbonate apatite layer on glass particles. Moreover, the investigated mesostructure showed a very good antibacterial effect against S. aureus strain, with a strong evidence of bactericidal activity already registered at 0.5 mg/mL of glass concentration. A hypothesis about the mechanism by which Ag affects the bacterial viability, based on the intermediate formation of crystalline AgCl, was also taken into account. With respect to what already reported in the literature, these findings claim a deeper insight into the possible use of silver-containing bioactive glasses as multifunctional ceramic coatings for orthopedic devices. PMID:23712538
Gargiulo, Nicola; Cusano, Angela Maria; Causa, Filippo; Caputo, Domenico; Netti, Paolo Antonio
Silica and phosphate based bioactive glass nanoparticles (58SiO2-33CaO-9P2O5) with doping of neem (Azadirachta indica) leaf powder and silver nanoparticles were prepared and characterised. Bioactive glass nanoparticles were produced using sol-gel technique. In vitro bioactivity of the prepared samples was investigated using simulated body fluid. X-ray diffraction (XRD) pattern of prepared glass particles reveals amorphous phase and spherical morphology with a particle size of less than 50?nm. When compared to neem doped glass, better bioactivity was attained in silver doped glass through formation of hydroxyapatite layer on the surface, which was confirmed through XRD, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM) analysis. However, neem leaf powder doped bioactive glass nanoparticles show good antimicrobial activity against Staphylococcus aureus and Escherichia coli and less bioactivity compared with silver doped glass particles. In addition, the biocompatibility of the prepared nanocomposites reveals better results for neem doped and silver doped glasses at lower concentration. Therefore, neem doped bioactive glass may act as a potent antimicrobial agent for preventing microbial infection in tissue engineering applications. PMID:25276834
Prabhu, M; Ruby Priscilla, S; Kavitha, K; Manivasakan, P; Rajendran, V; Kulandaivelu, P
Silica and phosphate based bioactive glass nanoparticles (58SiO2-33CaO-9P2O5) with doping of neem (Azadirachta indica) leaf powder and silver nanoparticles were prepared and characterised. Bioactive glass nanoparticles were produced using sol-gel technique. In vitro bioactivity of the prepared samples was investigated using simulated body fluid. X-ray diffraction (XRD) pattern of prepared glass particles reveals amorphous phase and spherical morphology with a particle size of less than 50?nm. When compared to neem doped glass, better bioactivity was attained in silver doped glass through formation of hydroxyapatite layer on the surface, which was confirmed through XRD, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM) analysis. However, neem leaf powder doped bioactive glass nanoparticles show good antimicrobial activity against Staphylococcus aureus and Escherichia coli and less bioactivity compared with silver doped glass particles. In addition, the biocompatibility of the prepared nanocomposites reveals better results for neem doped and silver doped glasses at lower concentration. Therefore, neem doped bioactive glass may act as a potent antimicrobial agent for preventing microbial infection in tissue engineering applications. PMID:25276834
Prabhu, M.; Ruby Priscilla, S.; Kavitha, K.; Manivasakan, P.; Rajendran, V.; Kulandaivelu, P.
The aim of this study was to fabricate and characterize in vitro a novel composite scaffold that, combining good mechanical properties with a controlled and sustained release of bioactive pro-angiogenetic growth factors, should be useful for angiogenesis induction in organs/tissues in which is also necessary to give resistance and mechanical strength. Composite scaffolds, constituted by a synthetic biocompatible material, a poly(ether)urethane-polydimethylsiloxane blend, and a biological polymer, the fibrin, were manufactured by spray, phase-inversion technique. During the manufacturing process heparin and heparin-binding growth factors, such as VEGF(165) and bFGF, were incorporated into the fibrin layer. Microscopical examinations showed a homogeneous fibrin layer firmly adherent on top of the synthetic material. Tensile tests highlighted the high elasticity of the composite scaffold and its capability to maintain integrity up to high deformation. VEGF(165) and bFGF release were controlled by fibrinogen concentration, whereas it was not affected by heparin concentration, as revealed by ELISA assay. The biological activity of the released growth factors was maintained as demonstrated by HUVEC proliferation. Finally, scaffolds induced a low monocyte mRNA expression of inflammatory markers (IL-8, L-SEL, LFA-1 and iNOS). In conclusion, the new composite scaffolds, once implanted, providing a co-localization and temporal distribution of bioactive VEGF and bFGF in addition to good mechanical properties, may be useful to stimulate new vessels formation in ischemic tissues. PMID:19811766
Briganti, Enrica; Spiller, Dario; Mirtelli, Chiara; Kull, Silvia; Counoupas, Claudio; Losi, Paola; Senesi, Sonia; Di Stefano, Rossella; Soldani, Giorgio
Bioactive glass/ZrO2 composites for orthopaedic applications.
Binary biocomposites were realized by combining yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) with a bioactive glass matrix. Few works are available regarding composites containing zirconia and a relatively high content of glass because the resulting samples are usually biocompatible but not bioactive after thermal treatment. In the present research, the promising properties of the new BG_Ca-K glass, with its low tendency to crystallize and high apatite-forming ability, allowed us to sinter the composites at a relatively low temperature with excellent effects in terms of bioactivity. In addition, it was possible to benefit from the good mechanical behaviour of Y-TZP, thus obtaining samples with microhardness values that were among the highest reported in the literature. After a detailed analysis regarding the thermal behaviour of the composite powders, the sintered bodies were fully characterized by means of x-ray diffraction, SEM equipped with EDS, density measurements, volumetric shrinkage determination, mechanical testing and in vitro evaluation in a simulated body fluid (SBF) solution. According to the experimental results, the presence of Y-TZP improved the mechanical performance. Meanwhile, the BG_Ca-K glass, which mainly preserved its amorphous structure after sintering, provided the composites with a good apatite-forming ability in SBF. PMID:24343516
Bellucci, D; Sola, A; Cannillo, V
A solanesol-derived scaffold for multimerization of bioactive peptides.
A flexible molecular scaffold bearing varying numbers of terminal alkyne groups was synthesized in five steps from solanesol. R(CO)-MSH(4)-NH(2) ligands, which have a relatively low affinity for binding at the human melanocortin 4 receptor (hMC4R), were prepared by solid phase synthesis and were N-terminally acylated with 6-azidohexanoic acid. Multiple copies of the azide N(3)(CH(2))(5)(CO)-MSH(4)-NH(2) were attached to the alkyne-bearing, solanesol-derived molecular scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Control studies showed that the binding affinity of the triazole-containing ligand, CH(3)(CH(2))(3)(C(2)N(3))(CH(2))(5)(CO)-MSH(4)-NH(2), was not significantly diminished relative to the corresponding parental ligand, CH(3)(CO)-MSH(4)-NH(2). In a competitive binding assay with a Eu-labeled probe based on the superpotent ligand NDP-alpha-MSH, the monovalent and multivalent constructs appear to bind to hMC4R as monovalent species. In a similar assay with a Eu-labeled probe based on MSH(4), modest increases in binding potency with increased MSH(4) content per scaffold were observed. PMID:20701315
Alleti, Ramesh; Rao, Venkataramanarao; Xu, Liping; Gillies, Robert J; Mash, Eugene A
A Solanesol-derived Scaffold for Multimerization of Bioactive Peptides
A flexible molecular scaffold bearing varying numbers of terminal alkyne groups was synthesized in five steps from solanesol. R(CO)-MSH(4)-NH2 ligands, which have a relatively low affinity for binding at the human melanocortin 4 receptor (hMC4R), were prepared by solid phase synthesis and were N-terminally acylated using 6-azidohexanoic acid. Multiple copies of the azide N3(CH2)5(CO)-MSH(4)-NH2 were attached to the alkyne-bearing, solanesol-derived molecular scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Control studies showed that the binding affinity of the triazole-containing ligand, CH3(CH2)3(C2N3)(CH2)5(CO)-MSH(4)-NH2, was not significantly diminished relative to the corresponding parental ligand, CH3(CO)-MSH(4)-NH2. In a competitive binding assay using a Eu-labeled probe based on the superpotent ligand NDP-?-MSH, the monovalent and multivalent constructs appear to bind to hMC4R as monovalent species. In a similar assay using a Eu-labeled probe based on MSH(4), modest increases in binding potency with increased MSH(4) content per scaffold were observed. PMID:20701315
Alleti, Ramesh; Rao, Venkataramanarao; Xu, Liping; Gillies, Robert J.; Mash, Eugene A.
Processing, properties, and in vitro bioactivity of polysulfone-bioactive glass composites.
The mismatch between the mechanical properties of bioceramics and natural tissue has restricted in several cases a wider application of ceramics in medical and dental fields. To overcome this problem, polymer matrix composites can be designed to combine bioactive properties of some bioceramics with the superior mechanical properties of some engineering plastics. In this work, polymer particulate composites composed of a high mechanical-property polymer and bioactive glass particles were produced and both the in vitro bioactivity and properties of the system were investigated. Composites with different volume fraction and particle size were prepared. In vitro tests showed that hydroxy-carbonate-apatite can be deposited on the surface of a composite as early as 20 h in a simulated body fluid. Ionic evolution from a composite with 40% volume fraction of particles was demonstrated to be similar to bulk bioactive glasses. The mechanical properties of some of the obtained composites had values comparable with the ones reported for bone. Moreover, a physical model based on dynamical mechanical tests showed evidences that the interface of the composite was aiding in the stress transfer process. PMID:17031819
Orķfice, Rodrigo; Clark, Arthur; West, Jon; Brennan, Anthony; Hench, Larry
NASA Astrophysics Data System (ADS)
Bioactive glass is known for its potential as a bone scaffold due to its ability to stimulate osteogenesis and induce bone formation. Broadening this potential to include the differentiation of human mesenchymal stem cells (hMSCs) to bone cells will enhance the healing process in bone defects. The surface of bioactive glass made by the sol-gel technique with the composition of 70% SiO2-30% CaO (mol %) was grafted with 3 peptides sequences in different combinations from proteins (fibronectin BMP-2 and BMP-9) that are known to promote the adhesion, differentiation and osteogenesis process. The experiment was done in two forms, a 2D non-porous thin film and a 3D nano-macroporous structure. hMSCs were grown on the materials for a total of five weeks. The 2D materials were tested for the expression of 3 osteogenic markers (osteopontin, osteocalcin and osteonectin) through immunocytochemistry. The 3D forms were monitored for cell's adhesion, morphology, spreading and proliferation by scanning electron microscopy, in addition to proliferation assay and alkaline phosphatase activity measurement. Results showed that hMSCs poorly adhered to the 2D thin films, but the few cells survived showed enhanced expression of the osteogenic markers. On the 3D form, cells showed enhanced proliferation at week one and more survival of the cells on the materials grafted with the adhesion peptide for the successive weeks in comparison to the positive control samples. Enhanced alkaline phosphatase activity was also detected compared to the negative control samples but were still below the positive control samples. In conclusion, the peptide grafting could increase the effect of bioactive glass but more peptide combinations should be examined to improve the effects on the differentiation and osteogenic activity of the hMSCs.
Ammar, Mohamed
A Sucrose-derived Scaffold for Multimerization of Bioactive Peptides
A spherical molecular scaffold bearing eight terminal alkyne groups was synthesized in one step from sucrose. One or more copies of a tetrapeptide azide, either N3(CH2)5(C=O)-His-dPhe-Arg-Trp-NH2 (MSH4) or N3(CH2)5(C=O)-Trp-Met-Asp-Phe-NH2 (CCK4), were attached to the scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Competitive binding assays using Eu-labeled probes based on the superpotent ligands Ser-Tyr-Ser-Nle-Glu-His-dPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (NDP-?-MSH) and Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2 (CCK8) were used to study the interactions of monovalent and multivalent MSH4 and CCK4 constructs with Hek293 cells engineered to overexpress MC4R and CCK2R. All of the monovalent and multivalent MSH4 constructs exhibited binding comparable to that of the parental ligand, suggesting that either the ligand spacing was inappropriate for multivalent binding, or MSH4 is too weak a binder for a second ōanchoringö binding event to occur before the monovalently-bound construct is released from the cell surface. In contrast with this behavior, monovalent CCK4 constructs were significantly less potent than the parental ligand, while multivalent CCK4 constructs were as or more potent than the parental ligand. These results are suggestive of multivalent binding, which may be due to increased residence times for monovalently bound CCK4 constructs on the cell surface relative to MSH4 constructs, the greater residence time being necessary for the establishment of multivalent binding. PMID:21940174
Rao, Venkataramanarao; Alleti, Ramesh; Xu, Liping; Tafreshi, Narges K.; Morse, David L.; Gillies, Robert J.; Mash, Eugene A.
While tissue engineering is a promising alternative for treating critical-sized cranio-maxillofacial bone defects, improvements in scaffold design are needed. In particular, scaffolds that can precisely match the irregular boundaries of bone defects as well as exhibit an interconnected pore morphology and bioactivity would enhance tissue regeneration. In this study, a shape memory polymer (SMP) scaffold was developed exhibiting an open porous structure and the capacity to conformally "self-fit" into irregular defects. The SMP scaffold was prepared via photocrosslinking of poly(?-caprolactone) (PCL) diacrylate using a SCPL method, which included a fused salt template. A bioactive polydopamine coating was applied to coat the pore walls. Following exposure to warm saline at T>Ttrans (Ttrans=Tm of PCL), the scaffold became malleable and could be pressed into an irregular model defect. Cooling caused the scaffold to lock in its temporary shape within the defect. The polydopamine coating did not alter the physical properties of the scaffold. However, polydopamine-coated scaffolds exhibited superior bioactivity (i.e. formation of hydroxyapatite in vitro), osteoblast adhesion, proliferation, osteogenic gene expression and extracellular matrix deposition. PMID:25063999
Zhang, Dawei; George, Olivia J; Petersen, Keri M; Jimenez-Vergara, Andrea C; Hahn, Mariah S; Grunlan, Melissa A
A novel room temperature process was developed to produce a 3D porous magnesium phosphate (MgP) scaffold with high drug load/release efficiency for use in hard tissue regeneration through a combination of a paste extruding deposition (PED) system and cement chemistry. MgP scaffolds were prepared using a two-step process. The first step was fabrication of the 3D porous scaffold green body to control both the morphology and pore structure using a PED system without hardening. The second step was cementation, which was carried out by immersing the scaffold green body in the binder solution for hardening instead of the typical sintering process in ceramic scaffold fabrication. Separation of the manufacturing process and cement reaction was important to secure enough time to fabricate a 3D scaffold with various sizes and architectures under homogeneous extruding conditions. Because the whole process is carried out at room temperature, the bioactive molecules, which are easily denatured by heat, may apply to scaffolds during the process. Lysozyme was selected as a model bioactive substance to demonstrate the efficiency of this process; this was directly mixed into MgP powder to introduce homogeneous distribution in the scaffold. The extruding paste for the PED system was prepared using the MgP-lysozyme blended powder as starting materials. That is, both 3D scaffold fabrication and functionalization of the scaffold with bioactive substances could be carried out simultaneously. This process significantly enhanced both drug loading efficiency and release performance compared to the typical sintering process, where the drug is generally loaded by adsorption after heat treatment. The MgP scaffold developed in this study satisfied the required conditions for scaffolding in hard tissue regeneration in an ideal manner, including 3 dimensionally well-interconnected pore structures, favorable mechanical properties, biodegradability, good cell affinity and in vitro biocompatibility; thus, it has excellent potential for application in the field of biomaterials. PMID:24433911
Lee, Jongman; Farag, Mohammad Mahmoud; Park, Eui Kyun; Lim, Jiwon; Yun, Hui-Suk
Well-ordered mesoporous bioactive glasses (MBG): a promising bioactive drug delivery system.
The local drug release system is considered to be an alternative to treat the bone infection. In this paper, well-ordered mesoporous bioactive glasses (MBG) with high specific surface area have been synthesized in aqueous solution by a two-step acid-catalyzed self-assembly process combined with hydrothermal treatment. Gentamicin was encapsulated into the MBG by adsorption method and in vitro release of gentamicin from MBG was performed in distilled water and modified simulated body fluid (SBF), respectively. The results showed that the amount of drug loading of MBG was three times more than that of conventional sol-gel 58S. The outcomes of drug release in distilled water and in SBF showed that M58S effectively decreased the initial burst. During the release period, gentamicin was released from the M58S at a much lower release rate as compared to that from 58S after soaking in distilled water and SBF. Furthermore, the drug release was sensitive to the pH and ionic concentration of the release medium suggesting possible controls of the release rate. In addition, in contrast to conventional sol-gel 58S, M58S had higher ability to induce hydroxyapatite (HAp) formation. Therefore, well-ordered mesoporous bioactive glasses might be used as a bioactive drug release system for preparation of bone implant materials. PMID:16375986
Xia, Wei; Chang, Jiang
Bioactive glass coating: physicochemical aspects and biological findings.
Glass coating material was investigated before and after spraying to see whether it maintained the chemical and physical properties; in vivo and in vitro studies were done to evaluate the biological results. Following the spraying process, the Biovetro coating on the TiAl6V4 plate--as evidenced from chemical and physical analysis--maintains the properties of the original glass unchanged as far as the amorphous structure and its behaviour in a hydrolytic environment are concerned. In vitro and in vivo studies underline the positive features of the coating obtained by the plasma spray process, confirming that it has the typical properties of bioactive glass patented under the trade mark, Biovetro, i.e. biodegradability and osteoconductivity already confirmed by previous experimental protocols carried out by our group using powdered and fibre Biovetro. PMID:7492714
Gabbi, C; Cacchioli, A; Locardi, B; Guadagnino, E
A new class of bioactive glasses: calcium-magnesium sulfophosphates.
Low-melting ionic sulfophosphate glasses from the system P2O5-SO4-MO-Na2O (M?=?Zn(2+), Ca(2+) or Mg(2+)) have been previously shown by us to allow tuneable aqueous dissolution and also enable processing temperatures well below 400░C. Sulfate ions are extremely safe for use in the body as decades of use of calcium sulfate bone grafts testifies and there is no known limit on their adult oral toxicity. This glass system therefore offers great potential for use as biomaterials, especially in organic-inorganic hybrid systems such as glass-polymer composites for tissue engineering or drug encapsulation and delivery applications. A compositional region was identified where stable sulfophosphates of the type P2O5-SO4-(Ca, Mg, Zn)O-Na2O can be fabricated. For these glasses, the viscosity-temperature-dependence, glass transformation temperatures (Tg ) and the onset of crystallization were evaluated as the primary processing parameters. As a first step in exploring their potential as a biomaterial, in this study we examine the bioactivity of several compositions of these glasses using fibroblast, monocyte, and osteoclast cell culture models to determine cellular responses in terms of attachment, proliferation, differentiation, and toxicity. PMID:24115563
Bassett, David C; Meszaros, Robert; Orzol, Dominik; Woy, Michel; Zhang, Yu Ling; Tiedemann, Kerstin; Wondraczek, Lothar; Komarova, Svetlana; Barralet, Jake E
Fine-tuning of bioactive glass for root canal disinfection.
An ideal preparation of 45S5 bioactive glass suspensions/slurries for root canal disinfection should combine high pH induction with capacity for continuing release of alkaline species. The hypothesis of this study was that more material per volume of bioactive glass slurry is obtained with a micrometric material (< 5 microm particle size) or a micrometric/ nanometric hybrid, rather than a solely nanometric counterpart. This should correlate with alkaline capacity and antimicrobial effectiveness. Slurries at the plastic limit were prepared with test and reference materials in physiological saline. Total mass and specific surface area of glass material per volume were determined. Continuous titration with hydrochloric acid was performed, and antimicrobial effectiveness was tested in extracted human premolars mono-infected with E. faecalis ATTC 29212 (N = 12 per material). While the nanometric slurry had a 12-fold higher specific surface area than the micrometric counterpart, the latter had a considerably higher alkaline capacity and disinfected significantly better (Fisher's exact test, P < 0.05). The hybrid slurry behaved similarly to the micrometric preparation. PMID:19329456
Waltimo, T; Mohn, D; Paquķ, F; Brunner, T J; Stark, W J; Imfeld, T; Schõtzle, M; Zehnder, M
Fluoride release and bioactivity evaluation of glass ionomer: Forsterite nanocomposite
Background: The most important limitation of glass ionomer cements (GICs) is the weak mechanical properties. Our previous research showed that higher mechanical properties could be achieved by addition of forsterite (Mg2SiO4) nanoparticles to ceramic part of GIC. The objective of the present study was to fabricate a glass ionomer- Mg2SiO4 nanocomposite and to evaluate the effect of addition of Mg2SiO4 nanoparticles on bioactivity and fluoride release behavior of prepared nanocomposite. Materials and Methods: Forsterite nanoparticles were made by sol-gel process. X-ray diffraction (XRD) technique was used in order to phase structure characterization and determination of grain size of Mg2SiO4 nanopowder. Nanocomposite was fabricated via adding 3wt.% of Mg2SiO4 nanoparticles to ceramic part of commercial GIC (Fuji II GC). Fluoride ion release and bioactivity of nanocomposite were measured using the artificial saliva and simulated body fluid (SBF), respectively. Bioactivity of specimens was investigated by Fourier transitioned-infrared spectroscopy (FTIR), scanning electronmicroscopy (SEM), Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and registration of the changes in pH of soaking solution at the soaking period. Statistical analysis was carried out by one Way analysis of variance and differences were considered significant if P < 0.05. Results: The results of XRD analysis confirmed that nanocrystalline and pure Mg2SiO4 powder was obtained. Fluoride ion release evaluation showed that the values of released fluoride ions from nanocomposite are somewhat less than Fuji II GC. SEM images, pH changes of the SBF and results of the ICP-OES and FTIR tests confirmed the bioactivity of the nanocomposite. Statistical analysis showed that the differences between the results of all groups were significant (P < 0.05). Conclusion: Glass ionomer- Mg2SiO4 nanocomposite could be a good candidate for dentistry and orthopedic applications, through of desirable fluoride ion release and bioactivity. PMID:24130579
Sayyedan, Fatemeh Sadat; Fathi, Mohammadhossein; Edris, Hossein; Doostmohammadi, Ali; Mortazavi, Vajihesadat; Shirani, Farzaneh
In cartilage regeneration, bio-activated implants are used in stem and progenitor cell-based microfracture cartilage repair procedures. Our aim was to analyze the chondrogenic potential of freeze-dried resorbable polymer-based polyglycolic acid (PGA) scaffolds bio-activated with transforming growth factor-?3 (TGFB3) on human subchondral mesenchymal progenitor cells known from microfracture. Progenitor cells derived from femur heads were cultured in the presence of freeze-dried TGFB3 in high-density pellet culture and in freeze-dried TGFB3-PGA scaffolds for chondrogenic differentiation. Progenitor cell cultures in PGA scaffolds as well as pellet cultures with and without continuous application of TGFB3 served as controls. Release studies showed that freeze-dried TGFB3-PGA scaffolds facilitate a rapid, initial boost-like release of 71.5% of TGFB3 in the first 10Āh. Gene expression analysis and histology showed induction of typical chondrogenic markers like type II collagen and formation of cartilaginous tissue in TGFB3-PGA scaffolds seeded with subchondral progenitor cells and in pellet cultures stimulated with freeze-dried TGFB3. Chondrogenic differentiation in freeze-dried TGFB3-PGA scaffolds was comparable to cultures receiving TGFB3 continuously, while non-stimulated controls did not show chondrogenesis during prolonged culture for 14Ādays. These results suggest that bio-activated, freeze-dried TGFB3-PGA scaffolds have chondrogenic potential and are a promising tool for stem cell-mediated cartilage regeneration. PMID:25169425
Kr³ger, Jan Philipp; Machens, Isabel; Lahner, Matthias; Endres, Michaela; Kaps, Christian
Two glass-ceramic scaffolds with a simple cubic structure of 500 Ąm square ligaments and square channels of width 400 or 600 Ąm have been fabricated by gel-casting into moulds produced by stereolithography, followed by mould removal, polymer burnout and sintering. The scaffolds have crushing strengths of 41 ▒ 14 and 17 ▒ 5 Mpa, respectively. Using a method of assembling discrete slices of scaffold, we are able to study cell behaviour within a scaffold by disassembly. Both scaffold structures were seeded with primary human osteoblasts and these penetrate, adhere, spread and proliferate on the scaffold structure. The larger channel diameter scaffold shows a greater cell population (despite its smaller surface area) and more pronounced production of ECM components (collagen and mineralization) with increased time in culture. Studies of sectioned scaffolds show that cell density and ECM production decrease with depth and that the difference between the two scaffold architectures is maintained. PMID:23013914
Chopra, K; Mummery, P M; Derby, B; Gough, J E
Development of nano-macroporous soda-lime phosphofluorosilicate bioactive glass and glass-ceramics
We have extended the usefulness of bioactive glass-ceramics for the repair and reconstruction of hard tissues by introducing\\u000a F ions that are known to be beneficial, especially in dentistry. Nano-macro multimodal porosity in soda-lime phosphofluorosilicate\\u000a bulk samples was introduced by the recently developed melt-quench-heat-etch method. The choice of starting glass composition\\u000a is based on 48SiO2¢2.7P2O5¢xCaF2¢yCaO¢zNa2O where xĀ=Ā0, 1, 4, 8,
H. M. M. Moawad; H. Jain
Porous poly(L-lactic acid) (PLLA) scaffolds with bioactive coatings were prepared by a novel one-step method. In this process, ice-based microporogens containing bioactive molecules, such as hydroxyapatite (HA) and collagen, served as both porogens to form the porous structure and vehicles to transfer the bioactive molecules to the inside of PLLA scaffolds in a single step. Based on scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis, the bioactive components were found to be transferred successfully from the porogens to PLLA scaffolds evenly. Osteoblast cells were used to evaluate the cellular behaviors of the composite scaffolds. After 8 days culturing, MTT assay and alkaline phosphatase (ALP) activity results suggested that HA/collagen could improve the interactions between osteoblast cells and the polymeric scaffold. PMID:20004261
Li, Jiashen; Chen, Yun; Mak, Arthur F.T.; Tuan, Rocky S.; Li, Lin; Li, Yi
Bone loss is a significant clinical problem, and treatments utilizing donated graft material are limited. To meet future demands in the healthcare industry, there has been a shift of outlook toward the use of bioactive materials for tissue regeneration. A number of in vivo and in vitro studies have highlighted the potential of the bioactive glass ceramic 45S5 Bioglass as a synthetic regenerative scaffold. The application of sol-gel processing techniques has led to the synthesis of mesoporous bioactive glasses with greater textural and compositional variety. In this study, we evaluated the effects of supplemented tissue culture medium containing up to 203 ppm silica prepared by static soaking of particles of 58S sol-gel bioactive glass (58% SiO(2), 33% CaO, 9% P(2)O(5)) on the in vitro proliferation and differentiation of murine and human primary osteoblasts. These extracts had a higher silica content than those used previously in studies of 45S5 Bioglass, because of the faster rates of ion exchange permitted by the higher surface area-to-volume ratio of mesoporous glass. We found that osteoblasts from both species increased their proliferation in response to the glass-conditioned medium. In addition, the extent to which supplemented medium could alter cell differentiation varied with time in culture. Proliferation induced by supplemented medium paralleled effects induced by treatment with basic fibroblast growth factor, a known mitogenic growth factor for osteoblasts. Bone nodule formation was also increased by exposure to the glass-conditioned medium and this effect was positively correlated with the dose of glass used to prepare the medium. Apoptosis was stimulated by glass-conditioned medium in murine osteoblasts, but inhibited in human osteoblasts. These data demonstrate the bioactive effects of dissolution products derived from sol-gel materials on primary osteoblasts and complements in vivo studies that indicate the suitability of this material as a bone graft substitute. PMID:15363159
Bielby, Robert C; Christodoulou, Ioannis S; Pryce, Russell S; Radford, Warwick J P; Hench, Larry L; Polak, Julia M
Development of nano-macroporous soda-lime phosphofluorosilicate bioactive glass and glass-ceramics.
We have extended the usefulness of bioactive glass-ceramics for the repair and reconstruction of hard tissues by introducing F ions that are known to be beneficial, especially in dentistry. Nano-macro multimodal porosity in soda-lime phosphofluorosilicate bulk samples was introduced by the recently developed melt-quench-heat-etch method. The choice of starting glass composition is based on 48SiO2-2.7P2O5-xCaF2-yCaO-zNa2O where x = 0, 1, 4, 8, 10, 12, and (y + z) = 49.3-x (mol%). The effect of thermal and chemical treatment on the microstructure of samples is characterized by SEM, XRD and EDX. We find the formation of many crystalline phases, but mainly sodium calcium silicate, calcium phosphate, fluorapatite and calcium silicate. The bioactivity of soda-lime phosphofluorosilicate glass-ceramics is assessed by monitoring the formation of hydroxyl apatite (HA) layer: fluorapatite phase accelerates the rate of HA layer formation; the initial composition and multi-modal porosity are other key parameters that impact the formation of HA. The present porous glass-ceramics should be superior candidates for use in dental bone regeneration. PMID:19252969
Moawad, H M M; Jain, H
Capacity of mesoporous bioactive glass nanoparticles to deliver therapeutic molecules.
Inorganic bioactive nanomaterials are attractive for hard tissue regeneration, including nanocomponents for bone replacement composites and nanovehicles for delivering therapeutics. Bioactive glass nanoparticles (BGn) have recently gained potential usefulness as bone and tooth regeneratives. Here we demonstrate the capacity of the BGn with mesopores to load and deliver therapeutic molecules (drugs and particularly genes). Spherical BGn with sizes of 80-90 nm were produced to obtain 3-5 nm sized mesopores through a sono-reacted sol-gel process. A simulated body fluid test of the mesoporous BGn confirmed their excellent apatite forming ability and the cellular toxicity study demonstrated their good cell viability up to 100 ?g ml(-1). Small molecules like chemical drug (Na-ampicillin) and gene (small interfering RNA; siRNA) were introduced as model drugs considering the mesopore size of the nanoparticles. Moreover, amine-functionalization allowed switchable surface charge property of the BGn (from -20-30 mV to +20-30 mV). Loading of ampicillin or siRNA saturated within a few hours (~2 h) and reflected the mesopore structure. While the ampicillin released relatively rapidly (~12 h), the siRNA continued to release up to 3 days with almost zero-order kinetics. The siRNA-nanoparticles were easily taken up by the cells, with a transfection efficiency as high as ~80%. The silencing effect of siRNA delivered from the BGn, as examined by using bcl-2 model gene, showed dramatic down-regulation (~15% of control), suggesting the potential use of BGn as a new class of nanovehicles for genes. This, in conjunction with other attractive properties, including size- and mesopore-related high surface area and pore volume, tunable surface chemistry, apatite-forming ability, good cell viability and the possible ion-related stimulatory effects, will potentiate the usefulness of the BGn in hard tissue regeneration. PMID:23100043
El-Fiqi, Ahmed; Kim, Tae-Hyun; Kim, Meeju; Eltohamy, Mohamed; Won, Jong-Eun; Lee, Eun-Jung; Kim, Hae-Won
Bioactive materials such as hydroxyapatite (HA) are used as coatings on metallic implants, producing a conjugate with better performance. The coatings are in general obtained by a plasma spray process. In this work the structural properties of composite coatings hydroxyapatite\\/bioactive glass (HA\\/BG) as well as coatings of the pure materials are measured. The coatings were obtained by plasma spraying mixtures
Flßvio L. S Carvalho; Christiano S Borges; Josķ Roberto T Branco; Marivalda M Pereira
Borophosphate glass-ceramic scaffolds by a sodium silicate bonding process
A borophosphate glass with the mol% composition 25Na2O-25CaO-5P2O3-45B2O5 was melted. The crystalline phase rheanite crystallized spontaneously during cooling the sample. Porous glass-ceramic scaffolds were prepared by bonding glass particles with size distributions in the range of approximately 100¢500?m by 0.1M Na2SiO3 solutions. The scaffolds porosities were 40~60% and their compressive strengths were 0.1~0.4MPa. The conversion of the binding scaffolds to
Wen Liang; Yifan Tu; Huanjun Zhou; Changsheng Liu; Christian R³ssel
Subcutaneous connective tissue reactions to three types of bioactive glass nanopowders.
Silica-based bioactive glasses are considered promising bone substitutes and tissue regeneration matrices, because of their bioactivity, biocompatibility, osteoconductivity, and possibly even osteoinductivity. The aim of this work was to evaluate the subcutaneous connective tissue reactions to 58S, 63S, and 72S bioactive glass nanopowders. Our previous study showed the antibacterial activities of 58S and 63S bioactive glass nanopowders on aerobic bacteria, while 72S showed no antibacterial effects at all. Bioactive glass nanopowders were prepared via the sol-gel technique. Characterization techniques such as X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and X-ray fluorescent (XRF) were utilized to carry out the phase analysis, study of the structure, particle size and the composition of the synthesized bioactive glasses. To evaluate the subcutaneous connective tissue reactions, the specimens were placed in polyethylene tubes and implanted into the dorsal connective tissue of rats. Empty polyethylene tubes were used as the control and bioactive glass micropowders (NovaBone) was used as a FDA approved bone graft. The evaluation of inflammatory reactions was performed 3, 7, 15, and 28 days after implantation. Results showed a particle size of below 100 nm for samples with amorphous structure. The samples were well tolerated by the tissues over a 28-day evaluation period. The extra tissue reactions of the 72S specimen in comparison with 58S and 63S specimens could be attributed to its higher silica content. It may be concluded that biocompatible 58S and 63S bioactive glass nanopowders with antibacterial activities can be synthesized for the treatment of osseous defects. PMID:21830490
Mehdikhani-Nahrkhalajil, M; Fathi, M H; Mortazavi, V; Mousavi, S B; Razavi, S M
Bioactive glasses are able to bond to bone through the formation of hydroxy-carbonate apatite in body fluids while strontium (Sr)-releasing bioactive glasses are of interest for patients suffering from osteoporosis, as Sr was shown to increase bone formation both in vitro and in vivo. A melt-derived glass series (SiO2¢P2O5¢CaO¢Na2O) with 0¢100% of calcium (Ca) replaced by Sr on a molar base was prepared. pH change, ion release and apatite formation during immersion of glass powder in simulated body fluid and Tris buffer at 37░C over up to 8 h were investigated and showed that substituting Sr for Ca increased glass dissolution and ion release, an effect owing to an expansion of the glass network caused by the larger ionic radius of Sr ions compared with Ca. Sr release increased linearly with Sr substitution, and apatite formation was enhanced significantly in the fully Sr-substituted glass, which allowed for enhanced osteoblast attachment as well as proliferation and control of osteoblast and osteoclast activity as shown previously. Studying the composition¢structure¢property relationship in bioactive glasses enables us to successfully design next-generation biomaterials that combine the bone regenerative properties of bioactive glasses with the release of therapeutically active Sr ions. PMID:21993007
Fredholm, Yann C.; Karpukhina, Natalia; Brauer, Delia S.; Jones, Julian R.; Law, Robert V.; Hill, Robert G.
Bioactive glasses are able to bond to bone through the formation of hydroxy-carbonate apatite in body fluids while strontium (Sr)-releasing bioactive glasses are of interest for patients suffering from osteoporosis, as Sr was shown to increase bone formation both in vitro and in vivo. A melt-derived glass series (SiO(2)-P(2)O(5)-CaO-Na(2)O) with 0-100% of calcium (Ca) replaced by Sr on a molar base was prepared. pH change, ion release and apatite formation during immersion of glass powder in simulated body fluid and Tris buffer at 37░C over up to 8 h were investigated and showed that substituting Sr for Ca increased glass dissolution and ion release, an effect owing to an expansion of the glass network caused by the larger ionic radius of Sr ions compared with Ca. Sr release increased linearly with Sr substitution, and apatite formation was enhanced significantly in the fully Sr-substituted glass, which allowed for enhanced osteoblast attachment as well as proliferation and control of osteoblast and osteoclast activity as shown previously. Studying the composition-structure-property relationship in bioactive glasses enables us to successfully design next-generation biomaterials that combine the bone regenerative properties of bioactive glasses with the release of therapeutically active Sr ions. PMID:21993007
Fredholm, Yann C; Karpukhina, Natalia; Brauer, Delia S; Jones, Julian R; Law, Robert V; Hill, Robert G
Scalable expansion of cells for regenerative cell therapy or to produce large quantities for high-throughput screening remains a challenge for bioprocess engineers. Laboratory scale cell expansion using t-flasks requires frequent passaging that exposes cells to many poorly defined bioprocess forces that can cause damage or alter their phenotype. Microcarriers offer a potential solution to scalable production, lending themselves to cell culture processes more akin to fermentation, removing the need for frequent passaging throughout the expansion period. One main problem with microcarrier expansion, however, is the difficulty in harvesting cells at the end of the process. Therefore, therapies that rely on cell delivery using biomaterial scaffolds could benefit from a microcarrier expansion system whereby the cells and microcarriers are transplanted together. In the current study, we used bioactive glass microcarriers doped with 5% TiO2 that display a controlled rate of degradation and conducted experiments to assess biocompatibility and growth of primary fibroblast cells as a model for cell therapy products. We found that the microcarriers are highly biocompatible and facilitate cell growth in a gradual controlled manner. Therefore, even without additional biofunctionalization methods, Ti-doped bioactive glass microcarriers offer potential as a cell expansion platform. PMID:22935537
Guedes, Joana C; Park, Jeong-Hui; Lakhkar, Nilay J; Kim, Hae-Won; Knowles, Jonathan C
Scalable expansion of cells for regenerative cell therapy or to produce large quantities for high-throughput screening remains a challenge for bioprocess engineers. Laboratory scale cell expansion using t-flasks requires frequent passaging that exposes cells to many poorly defined bioprocess forces that can cause damage or alter their phenotype. Microcarriers offer a potential solution to scalable production, lending themselves to cell culture processes more akin to fermentation, removing the need for frequent passaging throughout the expansion period. One main problem with microcarrier expansion, however, is the difficulty in harvesting cells at the end of the process. Therefore, therapies that rely on cell delivery using biomaterial scaffolds could benefit from a microcarrier expansion system whereby the cells and microcarriers are transplanted together. In the current study, we used bioactive glass microcarriers doped with 5% TiO? that display a controlled rate of degradation and conducted experiments to assess biocompatibility and growth of primary fibroblast cells as a model for cell therapy products. We found that the microcarriers are highly biocompatible and facilitate cell growth in a gradual controlled manner. Therefore, even without additional biofunctionalization methods, Ti-doped bioactive glass microcarriers offer potential as a cell expansion platform. PMID:22935537
Guedes, Joana C; Park, Jeong-Hui; Lakhkar, Nilay J; Kim, Hae-Won; Knowles, Jonathan C; Wall, Ivan B
To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of early host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1? and IL-10 are important cytokines in tissue responses to biomaterials because IL-1? promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1? was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1- and M2-macrophage-related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these genetic regulations. PMID:24454803
Ehashi, Tomo; Takemura, Taro; Hanagata, Nobutaka; Minowa, Takashi; Kobayashi, Hisatoshi; Ishihara, Kazuhiko; Yamaoka, Tetsuji
A 3D-glass-ceramic scaffold for bone tissue engineering with an interconnected macroporous network of pores was doped with silver ions in order to confer antibacterial properties. For this purpose, silver ions were selectively added to the scaffold surfaces through ion-exchange using an aqueous silver nitrate solution. The silver-doped scaffolds were characterized by means of leaching, in vitro antibacterial, and citotoxicity tests. In particular, the silver effect was examined through a broth dilution test in order to evaluate the proliferation of bacteria by counting the colonies forming units. Moreover, cytotoxicity tests were carried out to understand the effect of silver-containing scaffolds on cell adhesion, proliferation, and vitality. For all tests a comparison between silver-doped scaffold and silver-doped scaffold dry sterilized was performed. PMID:20207775
Balagna, Cristina; Vitale-Brovarone, Chiara; Miola, Marta; Vernķ, Enrica; Canuto, Rosa Angela; Saracino, Silvia; Muzio, Giuliana; Fucale, Giacomo; Maina, Giovanni
Bioactive glass-coated silicone for percutaneous devices with improved tissue interaction
NASA Astrophysics Data System (ADS)
The discovery of bioactive glasses, in the early 1970s, has produced a material that develops a strong adherent bond with soft tissue. Many medical applications currently use silicone as an implant material, but are hindered by the formation of fibrous scar tissue surrounding the device. This fibrous scar tissue can lead to pain, infection, and/or extrusion of these devices. Bioactive ceramic materials are inherently brittle and can not be used in applications where a flexible material is needed. Therefore, the coating of existing flexible silicone medical devices, like catheters, with a bioactive glass material would give the advantages of both. The research presented here is of methods used to coat silicone with a bioactive glass powder (Bioglass░ler) and the in vitro testing of those coatings. The bioactivity of these coatings was measured using scanning electron microscopy, inductively coupled plasma spectroscopy, and Fourier transform infrared spectroscopy. It was observed that hydroxyapatite, a bonelike apatite, was formed in vitro on both the bioactive glass particles and the silicone surface between these particles. From these results a new theory was developed that related the distance between particles on a surface with the formation of an apatite layer. A critical distance between particles for the formation of an apatite layer on the substrate exists. This critical distance is a function of both the particle size and composition. In addition, a method to coat silicone catheters with bioactive glass powder is also discussed. This coated catheter could ultimately be used for improved percutaneous access in peritoneal dialysis. The one barrier to greater peritoneal dialysis use and the reason many patients switch from peritoneal to hemodialysis is recurrent exit-site infections and subsequent peritonitis. These infections are caused by the lack of a tight seal and downgrowth of epidermal tissue around the catheter at the catheter-skin interface.
Marotta, James Scott
Biomaterials made of biodegradable poly(?-hydroxyesters) such as poly(lactide-co-glycolide) (PLGA) are known to decrease the pH in the vicinity of the implants. Bioactive glass (BG) is being investigated as a counteracting agent buffering the acidic degradation products. However, in dentistry the question arises whether an antibacterial effect is rather obtained from pure PLGA or from BG/PLGA composites, as BG has been proved to be antimicrobial. In the present study the antimicrobial properties of electrospun PLGA and BG45S5/PLGA fibres were investigated using human oral bacteria (specified with mass spectrometry) incubated for up to 24 h. BG45S5 nanoparticles were prepared by flame spray synthesis. The change in colony-forming units (CFU) of the bacteria was correlated with the pH of the medium during incubation. The morphology and structure of the scaffolds as well as the appearance of the bacteria were followed bymicroscopy. Additionally, we studied if the presence of BG45S5 had an influence on the degradation speed of the polymer. Finally, it turned out that the pH increase induced by the presence of BG45S5 in the scaffold did not last long enough to show a reduction in CFU. On the contrary, pure PLGA demonstrated antibacterial properties that should be taken into consideration when designing biomaterials for dental applications. PMID:23816650
Hild, Nora; Tawakoli, Pune N; Halter, Jonas G; Sauer, Bõrbel; Buchalla, Wolfgang; Stark, Wendelin J; Mohn, Dirk
Bioactive and bioresorbable cellular cubic-composite scaffolds for use in bone reconstruction
We used a novel composite fibre-precipitation method to create bioactive and bioresorbable cellular cubic composites containing calcium phosphate (CaP) particles (unsintered and uncalcined hydroxyapatite (u-HA), ?-tricalcium phosphate, ?-tricalcium phosphate, tetracalcium phosphate, dicalcium phosphate dihydrate, dicalcium phosphate anhydrate or octacalcium phosphate) in a poly-d/l-lactide matrix. The CaP particles occupied greater than or equal to 70?wt% (greater than or equal to 50?vol%) fractions within the composites. The porosities of the cellular cubic composites were greater than or equal to 70% and interconnective pores accounted for greater than or equal to 70% of these values. In vitro changes in the cellular geometries and physical properties of the composites were evaluated over time. The Alamar Blue assay was used to measure osteoblast proliferation, while the alkaline phosphatase assay was used to measure osteoblast differentiation. Cellular cubic C-u-HA70, which contained 70?wt% u-HA particles in a 30?wt% poly-d/l-lactide matrix, showed the greatest three-dimensional cell affinity among the materials tested. This composite had similar compressive strength and cellular geometry to cancellous bone, could be modified intraoperatively (by trimming or heating) and was able to form cortico-cancellous bone-like hybrids. The osteoinductivity of C-u-HA70, independent of biological growth factors, was confirmed by implantation into the back muscles of beagles. Our results demonstrated that C-u-HA70 has the potential as a cell scaffold or temporary hard-tissue substitute for clinical use in bone reconstruction. PMID:17015297
Shikinami, Yasuo; Okazaki, Kenshi; Saito, Makoto; Okuno, Masaki; Hasegawa, Shin; Tamura, Jiro; Fujibayashi, Shunsuke; Nakamura, Takashi
Purpose Poly(lactic-co-glycolic acid) (PLGA) is excellent as a scaffolding matrix due to feasibility of processing and tunable biodegradability, yet the virgin scaffolds lack osteoconduction and osteoinduction. In this study, nano-hydroxyapatite (nHA) was coated on the interior surfaces of PLGA scaffolds in order to facilitate in vivo bone defect restoration using biomimetic ceramics while keeping the polyester skeleton of the scaffolds. Methods PLGA porous scaffolds were prepared and surface modification was carried out by incubation in modified simulated body fluids. The nHA coated PLGA scaffolds were compared to the virgin PLGA scaffolds both in vitro and in vivo. Viability and proliferation rate of bone marrow stromal cells of rabbits were examined. The constructs of scaffolds and autogenous bone marrow stromal cells were implanted into the segmental bone defect in the rabbit model, and the bone regeneration effects were observed. Results In contrast to the relative smooth pore surface of the virgin PLGA scaffold, a biomimetic hierarchical nanostructure was found on the surface of the interior pores of the nHA coated PLGA scaffolds by scanning electron microscopy. Both the viability and proliferation rate of the cells seeded in nHA coated PLGA scaffolds were higher than those in PLGA scaffolds. For bone defect repairing, the radius defects had, after 12 weeks implantation of nHA coated PLGA scaffolds, completely recuperated with significantly better bone formation than in the group of virgin PLGA scaffolds, as shown by X-ray, Micro-computerized tomography and histological examinations. Conclusion nHA coating on the interior pore surfaces can significantly improve the bioactivity of PLGA porous scaffolds. PMID:23690683
Wang, De-Xin; He, Yao; Bi, Long; Qu, Ze-Hua; Zou, Ji-Wei; Pan, Zhen; Fan, Jun-Jun; Chen, Liang; Dong, Xin; Liu, Xiang-Nan; Pei, Guo-Xian; Ding, Jian-Dong
NASA Astrophysics Data System (ADS)
Bioactive glasses possess the ability to bond to living tissues through the formation of a calcium phosphate-rich layer at their interface with living tissues. This paper reports the different steps of this bioactivity process via a complete micro-PIXE characterization of a sol-gel derived SiO 2-CaO bioactive glass in contact with biological fluids for different delays. Multi-elemental cartography at the glass/biological fluids interface together with major and trace elements quantification permit a better understanding of the five reaction stages involved in the bioactivity mechanisms. The presence of phosphorus was detected at the periphery of the material within 6 h of interaction with biological fluids. A calcium phosphate-rich layer containing magnesium is formed after a few days of interaction and presence of bone-like apatite is deduced from the calculation of the Ca/P ratio at the material interface. That is of deep interest for clinical applications, because this biologically active behavior results in the formation of a strong interfacial bond between the glass and host tissues, and will stimulate bone-cell proliferation.
Lao, J.; Nedelec, J. M.; Moretto, Ph.; Jallot, E.
Image-Based Three-Dimensional Analysis to Characterize the Texture of Porous Scaffolds
The aim of the present study is to characterize the microstructure of composite scaffolds for bone tissue regeneration containing different ratios of chitosan/gelatin blend and bioactive glasses. Starting from realistic 3D models of the scaffolds reconstructed from micro-CT images, the level of heterogeneity of scaffold architecture is evaluated performing a lacunarity analysis. The results demonstrate that the presence of the bioactive glass component affects not only macroscopic features such as porosity, but mainly scaffold microarchitecture giving rise to structural heterogeneity, which could have an impact on the local cell-scaffold interaction and scaffold performances. The adopted approach allows to investigate the scale-dependent pore distribution within the scaffold and the related structural heterogeneity features, providing a comprehensive characterization of the scaffold texture. PMID:24995272
Pennella, Francesco; Gallo, Diego; Ciardelli, Gianluca; Bignardi, Cristina; Audenino, Alberto; Morbiducci, Umberto
Image-based three-dimensional analysis to characterize the texture of porous scaffolds.
The aim of the present study is to characterize the microstructure of composite scaffolds for bone tissue regeneration containing different ratios of chitosan/gelatin blend and bioactive glasses. Starting from realistic 3D models of the scaffolds reconstructed from micro-CT images, the level of heterogeneity of scaffold architecture is evaluated performing a lacunarity analysis. The results demonstrate that the presence of the bioactive glass component affects not only macroscopic features such as porosity, but mainly scaffold microarchitecture giving rise to structural heterogeneity, which could have an impact on the local cell-scaffold interaction and scaffold performances. The adopted approach allows to investigate the scale-dependent pore distribution within the scaffold and the related structural heterogeneity features, providing a comprehensive characterization of the scaffold texture. PMID:24995272
Massai, Diana; Pennella, Francesco; Gentile, Piergiorgio; Gallo, Diego; Ciardelli, Gianluca; Bignardi, Cristina; Audenino, Alberto; Morbiducci, Umberto
Preparation, Bioactivity and Antibacterial Effect of Bioactive Glass\\/Chitosan Biocomposites
In this study, we prepared BG filler powder containing some ions such as copper or zinc via sol gel method and their loading\\u000a onto chitosan polymeric matrix for improving their bioactivities as well as their effect onto microorganisms such as Staphylococcus\\u000a aureus bacteria were studied. The produced biocomposites characterized using X-ray diffraction (XRD), Fourier transformer\\u000a infrared spectra (FT-IR), Thermogravimetric (TGA)
Hanan H. Beherei; Khaled R. Mohamed; Amr I. Mahmoud
Bioactive glasses containing gold nanoparticles (AuNPs) have been synthesized via the sol-gel route using HAuCl(4) x 3 H(2)O as gold precursor. The formation process of AuNPs was studied as a function of the thermal treatment, which induces nucleation of Au particles and influences their nature, optical properties, shape, size, and distribution. The physicochemical characterization indicates that the sample treated at 600 degrees C presents the best characteristics to be used as a bioactive material, namely high surface area, high amount of AuNPs located at the glass surface, presence of micropores, and abundant surface OH groups. In the case of samples either aged at 60 degrees C or calcined at 150 degrees C, AuNPs just begin their formation, and at this stage the gel is not completely polymerized and dried yet. A thermal treatment at higher temperatures (900 degrees C) causes the aggregation of AuNPs, forming "AuMPs" (i.e., Au microparticles) in a densified glass-ceramic material with low surface area, absence of pores, and low number of surface OH groups. These features induce in the glass-ceramic materials treated at high-temperatures a lower bioactivity (evidenced by SBF reaction), as compared with that exhibited by the glass samples treated at 600 degrees C. PMID:20429543
Lusvardi, Gigliola; Malavasi, Gianluca; Aina, Valentina; Bertinetti, Luca; Cerrato, Giuseppina; Magnacca, Giuliana; Morterra, Claudio; Menabue, Ledi
structure. The kinetics of plasmid DNA release and its integrity are evaluated using fluorescently labeled) Objective: Polymer scaffolds serve a central role in tissue engineering. They function to create seeks to develop scaffolds that can also function as drug delivery vehicle for the localized, controlled
Shull, Kenneth R.
NASA Astrophysics Data System (ADS)
Development of bioactive glasses for use as a coating on Ti6Al4V prostheses requires a better understanding of reactions at the bone/bioactive glass interface. Indeed, the bioactive glasses bond to bone through physico-chemical reactions. In vivo, an apatite rich layer is built up on top of a pure silica rich layer at the bioactive glass periphery. In this paper, we have studied Ti6Al4V cylinders coated with a bioactive glass and implanted in sheep femora for two, three and six months. At each time period, the samples were analysed with scanning transmission electron microscopy coupled with energy dispersive x-ray spectroscopy. In vivo, the bioactive glass dissolution led to the formation on its surface of spherical particles with different sizes. The distributions of Si, Al, Ca, P and Mg concentrations across the particles reveal precipitation of apatite with the incorporation of magnesium. Apatite precipitation is governed by diffusion through an Si layer and occurs under specific supersaturation conditions. Measurements of supersaturation for Ca and P demonstrate that the largest precipitates grow and the smallest dissolve. These results allow us to study the growth and dissolution rate of the apatite precipitates and their relevance to bioactivity. Particles with a radius twice the average radius (
Jallot, E.; Benhayoune, H.; Kilian, L.; Irigaray, J. L.; Balossier, G.; Bonhomme, P.
Combining technologies to create bioactive hybrid scaffolds for bone tissue engineering.
Combining technologies to engineer scaffolds that can offer physical and chemical cues to cells is an attractive approach in tissue engineering and regenerative medicine. In this study, we have fabricated polymer-ceramic hybrid scaffolds for bone regeneration by combining rapid prototyping (RP), electrospinning (ESP) and a biomimetic coating method in order to provide mechanical support and a physico-chemical environment mimicking both the organic and inorganic phases of bone extracellular matrix (ECM). Poly(ethylene oxide terephthalate)-poly(buthylene terephthalate) (PEOT/PBT) block copolymer was used to produce three dimensional scaffolds by combining 3D fiber (3DF) deposition, and ESP, and these constructs were then coated with a Ca-P layer in a simulated physiological solution. Scaffold morphology and composition were studied using scanning electron microscopy (SEM) coupled to energy dispersive X-ray analyzer (EDX) and Fourier Tranform Infrared Spectroscopy (FTIR). Bone marrow derived human mesenchymal stromal cells (hMSCs) were cultured on coated and uncoated 3DF and 3DF + ESP scaffolds for up to 21 d in basic and mineralization medium and cell attachment, proliferation, and expression of genes related to osteogenesis were assessed. Cells attached, proliferated and secreted ECM on all the scaffolds. There were no significant differences in metabolic activity among the different groups on days 7 and 21. Coated 3DF scaffolds showed a significantly higher DNA amount in basic medium at 21 d compared with the coated 3DF + ESP scaffolds, whereas in mineralization medium, the presence of coating in 3DF+ESP scaffolds led to a significant decrease in the amount of DNA. An effect of combining different scaffolding technologies and material types on expression of a number of osteogenic markers (cbfa1, BMP-2, OP, OC and ON) was observed, suggesting the potential use of this approach in bone tissue engineering. PMID:23507924
Nandakumar, Anandkumar; Barradas, Ana; de Boer, Jan; Moroni, Lorenzo; van Blitterswijk, Clemens; Habibovic, Pamela
Structure, phases, and mechanical response of Ti-alloy bioactive glass composite coatings.
Porous titanium alloy-bioactive glass composite coatings were manufactured via the flame spray deposition process. The porous coatings, targeted for orthodontic and bone-fixation applications, were made from bioactive glass (45S5) powder blended with either commercially pure titanium (Cp-Ti) or Ti-6Al-4V alloy powder. Two sets of spray conditions, two metallic particle size distributions, and two glass particle size distributions were used for this study. Negative control coatings consisting of pure Ti-6Al-4V alloy or Cp-Ti were sprayed under both conditions. The as-sprayed coatings were characterized through quantitative optical cross-sectional metallography, X-ray diffraction (XRD), and ASTM Standard C633 tensile adhesion testing. Determination of the porosity and glassy phase distribution was achieved by using image analysis in accordance with ASTM Standard E2109. Theoretical thermodynamic and heat transfer modeling was conducted to explain experimental observations. Thermodynamic modeling was performed to estimate the flame temperature and chemical environment for each spray condition and a lumped capacitance heat transfer model was developed to estimate the temperatures attained by each particle. These models were used to establish trends among the choice of alloy, spray condition, and particle size distribution. The deposition parameters, alloy composition, and alteration of the feedstock powder size distribution had a significant effect on the coating microstructure, porosity, phases present, mechanical response, and theoretical particle temperatures that were attained. The most promising coatings were the Ti-6Al-4V-based composite coatings, which had bond strength of 20▒2MPa (n=5) and received reinforcement and strengthening from the inclusion of a glassy phase. It was shown that the use of the Ti-6Al-4V-bioactive glass composite coatings may be a superior choice due to the possible osteoproductivity from the bioactive glass, the potential ability to support tissue ingrowth and vascular tissue, and the comparable strength to similar coatings. PMID:24433912
Nelson, G M; Nychka, J A; McDonald, A G
Tissue adhesion to bioactive glass-coated silicone tubing in a rat model of peritoneal dialysis catheters and catheter tunnels.BackgroundSilicone peritoneal dialysis catheters do not develop tissue ingrowth, lack a mechanical barrier to periluminal bacterial migration and need cuffs for anchorage. We hypothesized that a bioactive glass coating composed of silicon, calcium, sodium and phosphorous oxides would cause a beneficial tissue reaction
Edward A Ross; Christopher D Batich; William L Clapp; Judith E Sallustio; Nadeen C Lee
Osteointegration of bioactive glass-coated zirconia in healthy bone: an in vivo evaluation.
Osteointegration of yttria stabilised tetragonal zirconia (YSTZ), either coated with bioactive glass named RKKP bioglaze (RKKP) or uncoated, was evaluated in an animal model. RKKP-coated and uncoated (controls) YSTZ cylinders were implanted in the distal femoral epiphyses of 14 Sprague Dawley rats under general anaesthesia. At the experimental times of 30 and 60 days after sacrifice, histomorphometry and SEM microanalysis were performed on methylmethacrylate-embedded undecalcified sections to determine the osteointegration rate. At 30 days, a significantly higher affinity index was demonstrated in vivo by histomorphometric evaluation in RKKP-coated versus uncoated YSTZ implants p < 0.05); at 60 days, the coated implants behaved better than controls (affinity index of + 32%), but the difference observed lay within the statistical uncertainty. SEM analysis demonstrated better bone adhesion to the material in RKKP-coated YSTZ at both 30 and 60 days. These findings suggest that YSTZ coated with the bioactive glass named RKKP enhances osteointegration of ceramics. PMID:12164187
Stanic, V; Aldini, N Nicoli; Fini, M; Giavaresi, G; Giardino, R; Krajewski, A; Ravaglioli, A; Mazzocchi, M; Dubini, B; Bossi, M G Ponzi; Rustichelli, F
Bioactive glass nanoparticles (BG-NPs), based on both ternary (SiO(2)-CaO-P(2)O(5)) and binary (SiO(2)-CaO) systems, were prepared via an optimized sol-gel method. The pH of preparation and the effect of heat treatment temperature were evaluated, as well as the effect of suppressing P in the bioactivity ability of the materials. The morphology and composition of the BG-NPs were studied using FTIR, XRD and SEM. The bioactive character of these materials was accessed inĀvitro by analyzing the ability for apatite formation onto the surface after being immersed in simulated body fluid (SBF). XRD, EDX and SEM were used to confirm the bioactivity of the materials. The BG-NP effect on cell metabolic activity was assessed by seeding L929 cells with their leachables, proving the non-cytotoxicity of the materials. Finally the most bioactive BG-NPs developed (ternary system prepared at pHĀ11.5 and treated at 700?░C) were successfully combined with chitosan in the production of biomimetic nanocomposite osteoconductive membranes that could have the potential to be used in guided tissue regeneration. PMID:22101770
Luz, Gisela M; Mano, JoŃo F
NASA Astrophysics Data System (ADS)
Bioactive glass nanoparticles (BG-NPs), based on both ternary (SiO2-CaO-P2O5) and binary (SiO2-CaO) systems, were prepared via an optimized sol-gel method. The pH of preparation and the effect of heat treatment temperature were evaluated, as well as the effect of suppressing P in the bioactivity ability of the materials. The morphology and composition of the BG-NPs were studied using FTIR, XRD and SEM. The bioactive character of these materials was accessed in vitro by analyzing the ability for apatite formation onto the surface after being immersed in simulated body fluid (SBF). XRD, EDX and SEM were used to confirm the bioactivity of the materials. The BG-NP effect on cell metabolic activity was assessed by seeding L929 cells with their leachables, proving the non-cytotoxicity of the materials. Finally the most bioactive BG-NPs developed (ternary system prepared at pH 11.5 and treated at 700 ░C) were successfully combined with chitosan in the production of biomimetic nanocomposite osteoconductive membranes that could have the potential to be used in guided tissue regeneration.
Luz, Gisela M.; Mano, JoŃo F.
Background Bioactive glass-ceramics have the ability to directly bind to bones and have been widely used as bone graft substitutes due to their high osteoconductivity and biocompatibility. CaO-SiO2-P2O5-B2O3 glass-ceramics are known to have good osteoconductivity and are used as bone graft extenders. Methods This study aimed to evaluate the effects of the resorbing properties of glass-ceramics in bone fusion after producing and analyzing three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with high osteoconductivity that had enhanced resorption by having an increased B2O3 content. The three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with B2O3 contents of 8.0, 9.0, and 9.5 weight % were designated and grouped as P20B80, P10B90, and P5B95, respectively. Glass-ceramic types were tested for fusion rates and bone formation by employing the lumbar 5-6 intertransverse process fusion model in 51 New Zealand male rabbits. Bioactivity was assessed by soaking in simulated body fluid (SBF). Results In vitro study results showed sufficient hydroxycarbonate apatite layer formation occurred for P20B80 in1 day, for P10B90 in 3 days, and for P5B95 in 5 days after soaking in SBF. For the rabbit lumbar spine posterolateral fusion model, the autograft group recorded a 100% fusion rate with levels significantly higher than those of P20B80 (29.4%), P10B90 (0%), and P5B95 (14.3%), with high resorbing properties. Resorbing property differences among the three glass-ceramic groups were not significant. Histological results showed new bone formation confirming osteoconductivity in all three types of glass-ceramics. Radiomorphometric results also confirmed the resorbing properties of the three glass-ceramic types. Conclusions The high resorbing properties and osteoconductivity of porous glass-ceramics can be advantageous as no glass-ceramics remain in the body. However, their relatively fast rate of resorption in the body negatively affects their role as an osteoconductive scaffold as glass-ceramics are resorbed before bony fusion. PMID:24605194
Lee, Jae Hyup; Ryu, Hyun-Seung; Seo, Jun-Hyuk; Lee, Do-Yoon; Chang, Bong-Soon
3D printing of bone substitute implants using calcium phosphate and bioactive glasses
Customized implants for bone replacement are a great help for a surgeon to remodel maxillofacial or craniofacial defects in an esthetical way, and to significantly reduce operation times. The hypothesis of this study was that a composite of ?-tricalcium phosphate (?-TCP) and a bioactive glass similar to the 45S5 Henchglass« is suitable to manufacture customized implants via 3D-printing process. The
Christian Bergmann; Markus Lindner; Wen Zhang; Karolina Koczur; Armin Kirsten; Rainer Telle; Horst Fischer
Crystal growth on bioactive glass sputter-coated alumina in artificial saliva.
In this work, a bioactive glass was deposited on the alumina disk specimens by radio-frequency magnetron sputtering to study crystal formation ability in artificial saliva. Bioactive glass-coated specimens were immersed in artificial saliva for 1 week and 6 months. The specimens were observed with a scanning electron microscope (SEM) and the composition was determined by energy dispersive spectroscopy (EDS). The crystals that formed on the specimens were analyzed by Raman spectroscopic analysis and Micro-X-ray diffraction. SEM photomicrographs showed the formation of needle-like structures after immersion for 1 week, and tabular structures formed on the surface of the specimen for 6 months. EDS showed that both the needle-like and tabular structures were enriched with Ca and P. Raman and Micro-XRD spectra for the tabular structure showed peaks that may correspond to calcium phosphate. Thus, when immersed in artificial saliva, bioactive glass-coated alumina produced a crystal which might be calcium phosphate. PMID:24088833
Iijima, Masahiro; Hashimoto, Masanori; Kohda, Naohisa; Nakagaki, Susumu; Muguruma, Takeshi; Endo, Kazuhiko; Mizoguchi, Itaru
The effect of phosphate content on the bioactivity of soda-lime-phosphosilicate glasses.
We report on the bioactivity of two series of glasses in the SiO(2)-Na(2)O-CaO-P(2)O(5) system after immersion in simulated body fluid (SBF) after 21 days. The effect of P(2)O(5) content was examined for compositions containing 0-9.25 mol.% phosphate. Both series of glasses degraded to basic pH, but the solutions tended towards to neutrality with increasing phosphate content; a result of the acidic phosphate buffering the effect of the alkali metal and alkaline earth ions on degradation. Bioactivity was assessed by the appearance of features in the X-ray diffraction (XRD) traces and Fourier transform infrared (FTIR) spectra consistent with crystalline hydroxyl-carbonate-apatite (HCAp): such as the appearance of the (002) Bragg reflection in XRD and splitting of the P-O stretching vibration around 550 cm(-1) in the FTIR respectively. All glasses formed HCAp in SBF over the time periods studied and the time for formation of this crystalline phase occurred more rapidly in both series as the phosphate contents were increased. For P(2)O(5) content >3 mol.% both series exhibited highly crystalline apatite by 16 h immersion in SBF. This indicates that in the compositions studied, phosphate content is more important for bioactivity than network connectivity (NC) of the silicate phase and compositions showing rapid apatite formation are presented, superior to 45S5 Bioglass which was tested under identical conditions for comparison. PMID:19330429
O'Donnell, M D; Watts, S J; Hill, R G; Law, R V
Antibacterial effects of sol-gel-derived bioactive glass nanoparticle on aerobic bacteria.
The aim of this work was to evaluate the antibacterial effect of bioactive glass nanopowders. The 58S, 63S, and 72S compositions were prepared via the sol-gel technique. Characterization techniques such as X-ray diffraction, transmission electron microscopy (TEM), Zetasizer, and X-ray fluorescent were used. The antibacterial activity was studied using Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Staphylococcus aureus. Cytotoxicity of the samples was evaluated using mouse fibroblast L929 cell line. The chemical compositions of the prepared samples were as predicted, and the particle size of the samples with an amorphous structure mainly ranged over 20-90 nm. At broth concentrations below 50 mg/mL, they showed no antibacterial activity. The 58S showed the highest antibacterial activity with the minimum bactericidal concentrations of 50 and 100 mg/mL for E. coli plus S. aureus and for P. aeruginosa, respectively. The 63S exhibited bactericidal and bacteriostatic effects on E. coli and S. aureus at concentrations of 100 and 50 mg/mL, respectively, at an minimum bactericidal concentrations of 100 mg/mL. However, 72S bioactive glass nanopowder showed no antibacterial effect. They showed no cytotoxicity. It was concluded that bioactive glass nanopowders could be considered as good candidates for the treatment of oral bone defects and root canal disinfection. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010. PMID:20127997
Mortazavi, V; Nahrkhalaji, M Mehdikhani; Fathi, M H; Mousavi, S B; Esfahani, B Nasr
Bioactive polymeric-ceramic hybrid 3D scaffold for application in bone tissue regeneration.
The regeneration of large bone defects remains a challenging scenario from a therapeutic point of view. In fact, the currently available bone substitutes are often limited by poor tissue integration and severe host inflammatory responses, which eventually lead to surgical removal. In an attempt to address these issues, herein we evaluated the importance of alginate incorporation in the production of improved and tunable ?-tricalcium phosphate (?-TCP) and hydroxyapatite (HA) three-dimensional (3D) porous scaffolds to be used as temporary templates for bone regeneration. Different bioceramic combinations were tested in order to investigate optimal scaffold architectures. Additionally, 3D ?-TCP/HA vacuum-coated with alginate, presented improved compressive strength, fracture toughness and Young's modulus, to values similar to those of native bone. The hybrid 3D polymeric-bioceramic scaffolds also supported osteoblast adhesion, maturation and proliferation, as demonstrated by fluorescence microscopy. To the best of our knowledge this is the first time that a 3D scaffold produced with this combination of biomaterials is described. Altogether, our results emphasize that this hybrid scaffold presents promising characteristics for its future application in bone regeneration. PMID:23910366
Torres, A L; Gaspar, V M; Serra, I R; Diogo, G S; Fradique, R; Silva, A P; Correia, I J
Effect of calcium source on structure and properties of sol-gel derived bioactive glasses.
The aim was to determine the most effective calcium precursor for synthesis of sol-gel hybrids and for improving homogeneity of sol-gel bioactive glasses. Sol-gel derived bioactive calcium silicate glasses are one of the most promising materials for bone regeneration. Inorganic/organic hybrid materials, which are synthesized by incorporating a polymer into the sol-gel process, have also recently been produced to improve toughness. Calcium nitrate is conventionally used as the calcium source, but it has several disadvantages. Calcium nitrate causes inhomogeneity by forming calcium-rich regions, and it requires high temperature treatment (>400 ░C) for calcium to be incorporated into the silicate network. Nitrates are also toxic and need to be burnt off. Calcium nitrate therefore cannot be used in the synthesis of hybrids as the highest temperature used in the process is typically 40-60 ░C. Therefore, a different precursor is needed that can incorporate calcium into the silica network and enhance the homogeneity of the glasses at low (room) temperature. In this work, calcium methoxyethoxide (CME) was used to synthesize sol-gel bioactive glasses with a range of final processing temperatures from 60 to 800 ░C. Comparison is made between the use of CME and calcium chloride and calcium nitrate. Using advanced probe techniques, the temperature at which Ca is incorporated into the network was identified for 70S30C (70 mol % SiO(2), 30 mol % CaO) for each of the calcium precursors. When CaCl(2) was used, the Ca did not seem to enter the network at any of the temperatures used. In contrast, Ca from CME entered the silica network at room temperature, as confirmed by X-ray diffraction, (29)Si magic angle spinning nuclear magnetic resonance spectroscopy, and dissolution studies. CME should be used in preference to calcium salts for hybrid synthesis and may improve homogeneity of sol-gel glasses. PMID:23171477
Yu, Bobo; Turdean-Ionescu, Claudia A; Martin, Richard A; Newport, Robert J; Hanna, John V; Smith, Mark E; Jones, Julian R
glass was obtained by melting a mixture of raw materials in a platinum crucible at high temperature (2STEM and EDXS characterisation of physico-chemical reactions at the periphery of bioactive glass and species of ions released at the bioactive glass particles/biological fluids interface is primordial
Boyer, Edmond
Polylactic acid¢phosphate glass composite foams as scaffolds for bone tissue engineering
Phosphate glass (PG) of the composition 0.46(CaO)- 0.04(Na2O)- 0.5(P2O5) was used as filler in poly-L-lactic acid (PLA) foams developed as degradable scaffolds for bone tissue engineering. The effect of PG on PLA was assessed both in bulk and porous composite foams. Composites with various PG content (0, 5, 10, and 20 wt %) were melt-extruded, and either compression-molded or foamed
G. Georgiou; L. Mathieu; D. P. Pioletti; P.-E. Bourban; J.-A. E. MÕnson; J. C. Knowles; S. N. Nazhat
Bioactive particles have been widely used in a series of biomedical applications due to their ability to promote bone-bonding and elicit favorable biological responses in therapies associated with the replacement and regeneration of mineralized tissues. In this work hierarchical architectures are prepared by an innovative methodology using SiO(2)-CaO sol-gel based nanoparticles. Inspired by colloidal crystals, spherical aggregates were formed on biomimetic superhydrophobic surfaces using bioactive glass nanoparticles (BG-NPs) able to promote bone regeneration. A highly ordered organization, a common feature of mineralized structures in Nature, was achieved at both nano- and microlevels, being the crystallization degree of the structures controlled by the evaporation rates taking place at room temperature (RT) or at 4 ░C. The crystallization degree of the structures influenced the Ca/P ratio of the apatitic film formed at their surface, after 7 days of immersion in SBF. This allows the regulation of bioactive properties and the ability to release potential additives that could be also incorporated in such particles with a high efficiency. Such a versatile method to produce bioactive particles with controlled size and internal structure could open new possibilities in designing new spherical devices for orthopaedic applications, including tissue engineering. PMID:22992681
Luz, Gisela M; Mano, JoŃo F
Hierarchical porous bioactive glasses/PLGA-magnetic SBA-15 for dual-drug release.
The hierarchical porous bioglass combined with magnetic SBA-15 was synthesized. The bioactive glass materials possess a hierarchical porous structure with the macroporous (50?m) and the mesoporous (3.86nm) structures derived from the plant template (cattail stem) and triblock polyethylene oxide-propylene oxide block copolymer (P123), respectively. Magnetic SBA-15 was synthesized by adopting the post assembly method using Fe(NO3)3 as iron source and ethylene glycol as reduction. After coating PLGA, PLGA-IBU-magnetic SBA-15 also possessed super-paramagnetism and the corresponding saturation magnetizations (Ms) could reach 2.6emug(-1). Metformin HCl (MH) and ibuprofen (IBU) were used as model drugs, and the drug release kinetics was studied. MH and IBU could release 60% and 85% from the sample respectively. The system shows excellent dual-drug controlled delivery performance and good bioactivity in vitro that leads to good potential application on bone regeneration. PMID:24863192
Ma, Jie; Lin, Huiming; Li, Xiaofeng; Bian, Chunhui; Xiang, Di; Han, Xiao; Wu, Xiaodan; Qu, Fengyu
Although the synthetic hydrogel materials capable of accelerating wound healing are being developed at a rapid pace, achieving inorganic-organic hybrid at nanoscale dimension in nanofibrous hydrogels is still a great challenge because of its notorious brittleness and microstructural stability in wet state. Here, we developed a new nanofibrous gelatin/bioactive glass (NF-GEL/BG) composite hydrogel by phase separation method and followed by arming the nanofibers network with counterionic chitosan-hyaluronic acid pairs for improving microstructural and thermal integrity. We achieve this feature by carrying an optimal balance of charges that allows the inorganic ion release in aqueous solution without minimal structure collapse. Therefore, such NF-GEL-based, polysaccharide-crosslinked bioactive hydrogel could afford a close biomimicry to the fibrous nanostructure and constituents of the hierarchically organized natural soft tissues to facilitate chronic, nonhealing wound treatment. PMID:23218343
Chen, Jian; Chen, Xiaoyi; Yang, Xianyan; Han, Chunmao; Gao, Changyou; Gou, Zhongru
Glass¢ceramic scaffolds mimicking the structure of cancellous bone were produced via sponge replication technique by using\\u000a a polyurethane foam as template and glass powder below 30Ā?m as inorganic phase. Specifically, a SiO2-based glass of complex composition and its corresponding P2O5-based ōspecularö glass were used as materials for scaffolding. The polymeric sponge was thermally removed and the glass powders\\u000a were sintered
Chiara Vitale-Brovarone; Francesco Baino; Oana Bretcanu; Enrica Vernķ
The objective of this study was to design a biomimetic and bioactive tissue-engineered bone construct via a cold atmospheric plasma (CAP) treatment for directed osteogenic differentiation of human bone morrow mesenchymal stem cells (MSCs). Porous nanocrystalline hydroxyapatite/chitosan scaffolds were fabricated via a lyophilization procedure. The nanostructured bone scaffolds were then treated with CAP to create a more favorable surface for cell attachment, proliferation, and differentiation. The CAP-modified scaffolds were characterized via scanning electron microscope, Raman spectrometer, contact angle analyzer, and white light interferometer. In addition, optimal CAP treatment conditions were determined. Our in vitro study shows that MSC adhesion and infiltration were significantly enhanced on CAP modified scaffolds. More importantly, it was demonstrated that CAP-modified nanostructured bone constructs can greatly promote total protein, collagen synthesis, and calcium deposition after 3 weeks of culture, thus making them a promising implantable scaffold for bone regeneration. Moreover, the fibronectin and vitronection adsorption experiments by enzyme-linked immunosorbent assay demonstrated that more adhesion-mediated protein adsorption on the CAP-treated scaffolds. Since the initial specific protein absorption on scaffold surfaces can lead to further recruitment as well as activation of favorable cell functions, it is suggested that our enhanced stem cell growth and osteogenic function may be related to more protein adsorption resulting from surface roughness and wettability modification. The CAP modification method used in this study provides a quick one-step process for cell-favorable tissue-engineered scaffold architecture remodeling and surface property alteration. PMID:24219622
Wang, Mian; Cheng, Xiaoqian; Zhu, Wei; Holmes, Benjamin; Keidar, Michael; Zhang, Lijie Grace
NASA Astrophysics Data System (ADS)
The incorporation of a bioactive glass in the structure of hybrid polymers used in dentistry for the construction of fixed prosthetic restorations could induce the expression of bioactivity, leading to the possibility of periodontal tissues reattachment. Hybrid polymer specimens and polymer specimens modified by bioactive glass were prepared and used as control for the surface morphology examination by Scanning Electron Microscopy with associated Dispersive Spectroscopy Analysis (SEM-EDS) and for surface characterization with Fourier Transform Infrared Spectroscopy (FTIR). Furthermore, hybrid polymer specimens modified by bioactive glass were immersed in simulated body fluid (SBF) at 37 ░C for different time intervals and were examined by SEM-EDS and FTIR. After 4 days immersion time a dense and continuous apatite layer covered almost the entire modified surface of the specimens. The molar Ca/P ratio reached the value of 1.79. The apatite layer showed a thickness of 1?m and was attached to the substrate, while bioactive glass particles were still present in polymer mass.
Georgantzi, B.; Papadopoulou, L.; Zorba, T.; Garefis, P.; Paraskevopoulos, K.; Koidis, P.
1 X-ray microanalysis in STEM of short-term physico-chemical reactions at bioactive glass particles Short-term physico-chemical reactions at the interface between bioactive glass particles and biological as « an interfacial bonding of an implant to tissue by means of formation of a biologically active hydroxyapatite
Paris-Sud XI, Universit├® de
The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli. PMID:23629702
Xie, Zongping; Cui, Xu; Zhao, Cunju; Huang, Wenhai; Wang, Jianqiang
In this study, six groups of modified ceramic specimens were constructed and were studied comparatively with dental porcelain (P:control) for their ability to support human periodontal ligament fibroblasts attachment and proliferation. The dental porcelain was initially coated with bioactive glass (PCB) or with a mixture of porcelain and bioactive glass (PCBP) and then calcium-phosphate rich (Ca-P) or hydroxy-carbonate apatite (HCAp) layers were bio-mimetically developed on both surfaces (PCB and PCBP) after immersion in simulated body fluid. The development and characterization of Ca-P and HCAp layers on PCBCa-P, PCBHCAp, PCBPCa-P, PCBPHCAp specimens' surfaces were evaluated by Scanning Electron Microscopy (SEM) and further confirmed by Fourier Transform Infrared Spectroscopy (FTIR). The modified ceramics differed from their controls concerning their surface morphology as evaluated by SEM, and their surface chemical composition (Al, P, Si, Ca, Na and K) as evaluated by Energy Dispersive Spectroscopy (EDS). Almost all modified specimens supported cell attachment, spreading and proliferation at higher extent than the control porcelain specimens. The additional layers of Ca-P or HCAp on PCBP and PCB specimens were found to positively affect cell attachment and proliferation. The highest cell population, of all specimens tested, was observed on PCBPCa-P and PCBPHCAp. The Ca-P particles present on all Ca-P and HCAp coated specimens seemed to be involved in cell adhesion. PMID:17207079
Kontonasaki, E; Sivropoulou, A; Papadopoulou, L; Garefis, P; Paraskevopoulos, K; Koidis, P
Various bioactive glass/hydroxyapatite (HA) functional coatings were designed by the suspension plasma spraying (SPS) technique. Their microstructure, scratch resistance, and apatite-forming ability in a simulated body fluid (SBF) were compared. The functional coatings design included: (i) composite coating, that is, randomly distributed constituent phases; (ii) duplex coating with glass top layer onto HA layer; and (iii) graded coating with a gradual changing composition starting from pure HA at the interface with the metal substrate up to pure glass on the surface. The SPS was a suitable coating technique to produce all the coating designs. The SBF tests revealed that the presence of a pure glass layer on the working surface significantly improved the reactivity of the duplex and graded coatings, but the duplex coating suffered a relatively low scratch resistance because of residual stresses. The graded coating therefore provided the best compromise between mechanical reliability and apatite-forming ability in SBF. ® 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 551-560, 2014. PMID:24123895
Cattini, Andrea; Bellucci, Devis; Sola, Antonella; Paw?owski, Lech; Cannillo, Valeria
Suspensions of micro- or nanoparticulate SiO(2)-Na(2)O-CaO-P(2)O(5) bioactive glasses could potentially be used as dressings in traumatized front teeth with open apices as an alternative to Ca(OH)(2). These materials have a disinfecting capacity similar to Ca(OH)(2), but bear the advantage of bioactivity. However, because bioactive glasses initially act as alkaline biocides just as Ca(OH)(2) does, they may also negatively affect mechanical dentin properties over time. This was assessed in the current study using standardized human root dentin bars. Specimens were immersed in 1:20 (wt vol(-1)) suspensions of nanometric bioactive glass 45S5 or calcium hydroxide for 1, 10, or 30 days. Control specimens were immersed in pure saline for 30 days (n = 20 per group). Subsequently, modulus of elasticity (E) and flexural strength (FS) of the specimens were determined. Results were compared between groups using one-way anova and Scheffķ's post-hoc test. Ca(OH)(2) caused a significant (P < 0.001) 35% drop in mean flexural strength values compared to the control treatment after 10 days. No further change was observed between 10 days and 30 days. Bioactive glass caused a 20% drop in mean flexural strength as compared to the control after 10 days. However, this difference did not reach statistical significance (P > 0.05). No effects of either material on dentin modulus of elasticity values were observed. It was concluded that the calcium hydroxide suspension affected the dentin more than the bioactive glass counterpart; however, the effect was self-limiting and probably restricted to superficial dentin layers, as suggested by the mere decrease in flexural strength but not in modulus of elasticity values. PMID:19208025
Marending, Monika; Stark, Wendelin J; Brunner, Tobias J; Fischer, Jens; Zehnder, Matthias
drug delivery; as such, mesoporous SiO2 glass has been proposed as a new class of bone regeneration '┐Į a marker of osteogenic cell differentiation '┐Į in human bone mesenchymal stem cells. Mesoporous Sr with properties suitable for bone regeneration need to be bioactive, and at the same time possess the capacity
Cuniberti, Gianaurelio
Covalent cyclization of peptides is an important tool in structure-function analysis of bioactive peptides, because it constrains the molecule to enrich or exclude the receptor-bound conformation. Previously we described a 2-step procedure for cyclizing purified, native peptides in aqueous solution by reacting a Met or Lys side chain with an iodoacetylated N-terminus (Wood SJ, Wetzel R, 1992a, Int J Pept Protein Res 39:533-539). We show here that the cyclization reaction scheme can be extended to peptides excised from proteins by endo-LysC proteolysis, which generates fragments terminating with Lys. To illustrate the method, we used an immunoglobulin VL domain (REI-VL) with an RGD-containing sequence engineered into its CDR3 and flanked by Lys residues. This REI-VL/RGD hybrid displayed an IC50 of 24 nM for ligand competition at the platelet fibrinogen receptor alpha IIb beta 3. The RGD-containing peptide excised by endo-LysC from the REI-VL presentation scaffold exhibited an IC50 of about 50 nM, and the corresponding cyclized peptide, and IC50 of about 10 nM. Significantly, both the N alpha-acylation and the cyclization reactions occur efficiently even in the context of the other endo-LysC fragments of REI-VL, which suggests that the reaction may prove useful in converting mixtures of endo-LysC products of many proteins into the corresponding cyclic peptides in situ. PMID:7920257
Helms, L. R.; Wetzel, R.
Bioactive glasses (SiO2-P2O5-CaO) having tailored concentrations of different biocide metal ions (copper or silver) were produced by the sol-gel method. All the particles release phosphorous ions when immersed in water and simulated body fluid (SBF). Moreover, a surface layer of polycrystalline hydroxy-carbonate apatite was formed on the particle surfaces after 10 day immersion in SBF as confirmed by X-ray diffraction and scanning electron microscopy (SEM) showing the bioactive materials. Samples with embedded either copper or silver ions were able to further release the biocide ions with a release rate that depends on the metal embedded and the dissolution medium: water or SBF. This biocide ion release from the samples explains the antimicrobial effect of our active particles against Escherichia coli DH5? ampicillin-resistant (Gram-negative) and Streptococcus mutans (Gram-positive) as determined by the Minimum Bactericidal Concentration (MBC) method. The antimicrobial behavior of the particles depends on the bacteria and the biocide ion used. Noteworthy, although samples with copper are able to release more metal ion than samples with silver, they present higher MBC showing the high effect of silver against these bacteria. PMID:23910279
Palza, Humberto; Escobar, Blanca; Bejarano, Julian; Bravo, Denisse; Diaz-Dosque, Mario; Perez, Javier
Gold nanoparticles developed in sol-gel derived apatite--bioactive glass composites.
The study is focussed on synthesis and characterisation of a new sol-gel derived composite system consisting of nanocrystalline apatite, bioactive glass and gold nanoparticles, which are of interest both for regenerative medicine and for specific medical applications of the releasable gold nanoparticles. Samples dried at 110░C and then heat treated for 30 min at 300 and 500░C were investigated by thermal analysis (DTA/TG), X-ray diffraction (XRD), UV-VIS-NIR, Fourier Transform Infrared (FTIR) spectroscopy, X-ray Photoelectron(XPS) spectroscopy, Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Gold nanoparticles and nanocrystalline apatite are developed already after heat treatment at 300░C. XPS analysis clearly revealed the presence of both metallic and ionic gold species. The development of gold nanoparticles was evidenced by UV-VIS-NIR and TEM analysis, and their size increased from few nanometers to 25 nm by increasing the treatment temperature from 300 to 500░C. The bioactivity of the samples immersed in simulated body fluid was demonstrated by XRD and SEM results. PMID:22395971
Simon, S; Ciceo-Lucacel, R; Radu, T; Baia, L; Ponta, O; Iepure, A; Simon, V
The ability of a silver-doped bioactive glass (AgBG) coating to prevent bacterial colonization on surgical sutures was investigated in vitro. Bioactive glass powders, in the form of 45S5 Bioglass and AgBG, were used to coat Mersilk sutures using an optimized 'in house' slurry-dipping process. In vitro experiments were carried out using Staphylococcus epidermidis under both batch and flow conditions. While the traditional batch culture testing was used to determine the number of viable cells adhered to the surface, the flow-cell was used to visualize attachment and detachment over time. Under batch conditions of up to 180 min, statistically significant differences were observed in the colony forming units (CFU) per suture for both the coated and uncoated Mersilk sutures. The results showed that the AgBG coating had the greatest effect on limiting bacterial attachment (8 x 10(2) CFU) when compared to the 45S5 Bioglass coating (3.2 x 10(3) CFU) and the uncoated Mersilk (1.2 x 10(4) CFU). Also under flow conditions differences were seen between the coated and uncoated sutures. Therefore, this preliminary study has demonstrated the quantification and visualization of bacterial attachment onto sutures in order to compare the antibacterial properties of Ag-containing bioactive glass coatings. The bactericidal properties imparted by Ag-containing glass open new opportunities for use of the composite sutures in wound healing and body wall repair. PMID:15245643
Pratten, Jonathan; Nazhat, Showan N; Blaker, Jonny J; Boccaccini, Aldo R
In this study, the cytotoxicity evaluation of prepared 63S bioactive glass and bone-derived hydroxyapatite particles with yeast and human chondrocyte cells was carried out using isothermal micro-nano calorimetry (IMNC), which is a new method for studying cell\\/biomaterial interactions. Bioactive glass particles were made via sol¢gel method and hydroxyapatite was obtained from bovine bone. Elemental analysis was carried out by XRF
A. Doostmohammadi; A. Monshi; M. H. Fathi; S. Karbasi; O. Braissant; A. U. Daniels
Melt-derived bioactive phosphosilicate glasses are widely utilized as bone-grafting materials for various surgical applications. However, the insight into their structural features over a medium-range scale up to ? 1 nm remains limited. We present a comprehensive assessment of the spatial distribution of phosphate groups across the structures of 11 Na2O-CaO-SiO2-P2O5 glasses that encompass both bioactive and nonbioactive compositions, with the P contents and silicate network connectivities varied independently. Both parameters are known to strongly influence the bioactivity of the glass in vitro. The phosphate distribution was investigated by double-quantum (31)P nuclear magnetic resonance (NMR) experiments under magic-angle spinning (MAS) conditions and by molecular dynamics (MD) simulations. The details of the phosphate-ion dispersion were probed by evaluating the MD-derived glass models against various scenarios of randomly distributed, as well as clustered, phosphate groups. From comparisons of the P-P interatomic-distance spreads and the statistics of small phosphate clusters assessed for variable cutoff radii, we conclude that the spatial arrangement of the P atoms in phosphosilicate glasses is well-approximated by a statistical distribution, particularly across a short-range scale of ? 450 pm. The primary distinction is reflected in slightly closer P-P interatomic contacts in the MD-derived structures over the distance span of 450-600 pm relative to that of randomly distributed phosphate groups. The nature of the phosphate-ion dispersion remains independent of the silicate network polymerization and nearly independent of the P content of the glass throughout our explored parameter space of 1-6 mol % P2O5 and silicate network connectivities up to 2.9. PMID:24967834
Stevensson, Baltzar; Mathew, Renny; Edķn, Mattias
The aim of this work was preparation, development and characterization of bioactive glass coating by sol¢gel technique for improvement of biocompatibility of 316L stainless steel implant used in dentistry and orthopaedic surgery.Bioglass powder was made by sol¢gel technique and thermal properties of the prepared powder were studied using differential thermal analysis (DTA). The prepared bioglass powder was immersed in the
M. H. Fathi; A. Doost Mohammadi
Effects of Bioactive Glass Scaffold and BMP-2 in Segmental Defects Wai-Ching Liu1
, Ming C. Leu2 , Mariano Valez3 , Tien-Min Chu1 1 Department of Restorative Dentistry, Indiana University. Mentor: Tien-Min Chu, Department of Restorative Dentistry, Indiana University School of Dentistry, IUPUI School of Dentistry; 2 Department of Mechanical and Aerospace Engineering, Missouri University of Science
Zhou, Yaoqi
Effect of ciprofloxacin incorporation in PVA and PVA bioactive glass composite scaffolds
agents for a prolonged time at the infection site and with low level of side effects may improve osteomyelitis treatment protocol combines both surgical removing of dead bone tissue and prolonged parenteral
Paris-Sud XI, Universit├® de
Bioactive glasses are used clinically for bone regeneration, and their bioactivity and cell compatibility are often characterized in vitro, using physiologically relevant test solutions. The aim of this study was to show the influence of varying medium characteristics (pH, composition, presence of proteins) on glass dissolution and apatite formation. The dissolution behavior of a fluoride-containing bioactive glass (BG) was investigated over a period of one week in Eagle's Minimal Essential Medium with Earle's Salts (MEM), supplemented with either, (a) acetate buffer, (b) 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, (c) HEPES + carbonate, or (d) HEPES + carbonate + fetal bovine serum. Results show pronounced differences in pH, ion release, and apatite formation over 1 week: Despite its acidic pH (pH 5.8 after BG immersion, as compared to pH 7.4-8.3 for HEPES-containing media), apatite formation was fastest in acetate buffered (HEPES-free) MEM. Presence of carbonate resulted in formation of calcite (calcium carbonate). Presence of serum proteins, on the other hand, delayed apatite formation significantly. These results confirm that the composition and properties of a tissue culture medium are important factors during in vitro experiments and need to be taken into consideration when interpreting results from dissolution or cell culture studies. PMID:23554092
Shah, Furqan A; Brauer, Delia S; Wilson, Rory M; Hill, Robert G; Hing, Karin A
Bioactive Glass Fiber Reinforced Starch-Polycaprolactone Composite for Bone Applications
NASA Astrophysics Data System (ADS)
For bone regeneration and repair, combinations of different materials are often needed. Biodegradable polymers are often combined with osteoconductive materials, such as bioactive glass (BaG), which can also improve the mechanical properties of the composite. The aim of this study was to develop and characterize BaG fiber-reinforced starch-poly-?-caprolactone (SPCL) composite. Sheets of SPCL (30/70 wt%) were produced using single-screw extrusion. They were then cut and compression molded in layers with BaG fibers to form composite structures of different combinations. Thermal, mechanical, and degradation properties of the composites were studied. The actual amount of BaG in the composites was determined using combustion tests. A strong endothermic peak indicating melting at about 56 ░C was observed by differential scanning calorimetry (DSC) analysis. Thermal gravimetry analysis (TGA) showed that thermal decomposition of SPCL started at 325 ░C with the decomposition of starch and continued at 400 ░C with the degradation of polycaprolactone (PCL). Initial mechanical properties of the reinforced composites were at least 50% better than the properties of the non-reinforced composites. However, the mechanical properties of the composites after two weeks of hydrolysis were comparable to those of the non-reinforced samples. During the six weeks' hydrolysis the mass of the composites had decreased only by about 5%. The amount of glass in the composites remained the same for the six-week period of hydrolysis. In conclusion, it is possible to enhance the initial mechanical properties of SPCL by reinforcing it with BaG fibers. However, the mechanical properties of the composites are only sufficient for use as filler material and they need to be further improved to allow long-lasting bone applications.
Jukola, H.; Nikkola, L.; Gomes, M. E.; Chiellini, F.; Tukiainen, M.; Kellomõki, M.; Chiellini, E.; Reis, R. L.; Ashammakhi, N.
[A novel europium doped apatite/wollastonite porous magnetic bioactive glass ceramic].
A new biocompatible apatite-wollastonite magnetic glass ceramic has been synthesized via sol-gel process. Characteristics of the materials were determined with differential thermal analysis (DTA), X-ray diffraction (XRD), scan electron microscopy (SEM), energy dispersive spectrum (EDS), inductively couple plasma atomic emission spectroscopy (ICP-AES), vibrating sample magnetometer (VSM) and so on. Results showed that the main crystalline phases of the material were hydroxyapatite/fluoroapatite [Ca10(PO4)6(OH, F)), beta-wollastonite[beta-CaSiO3] and calcium europium oxide silicate Ca2Eu8[(SiO4)6O2]. The magnetization of the sample contanining 2% Eu2O3 in weight reached 2.18 emu/g for an applied field of 10 000Oe. Hydroxyapatite layer could form on the surface of the sample while soaking for 14 days in simulated body fluid. Good bioactivity was demonstrated. So it is a potential bone repairing material as well as a hyperthemia treatment material for pateints with cancer. PMID:17899745
Zhang, Wangzhi; Zhou, Dali; Yang, Weizhong; Yin, Guangfu; Ou, Jun
Light-sensitive intelligent drug delivery systems of coumarin-modified mesoporous bioactive glass.
Functionalized mesoporous bioactive glasses (MBG) with photoactive coumarin demonstrates photo-responsive dimerization resulting in reversible gate operation. Coumarin-modified MBG was used as a drug delivery carrier to investigate drug storage/release characteristics using phenanthrene as a model drug. Irradiation with UV light (>310 nm) induced photo-dimerization of the coumarin-modified MBG, which led to the pores' closing with cyclobutane dimers and trapping of the guest phenanthrene in the mesopores. However, irradiating the dimerized-coumarin-modified MBG with shorter wavelength UV light (approximately 250 nm) regenerates the coumarin monomer derivative by the photo-cleavage of cyclobutane dimers, such that trapped guest molecules are released from the mesopores. The structural, morphological, textural and optical properties are well characterized by X-ray diffraction, transmission electron microscopy, N(2) adsorption/desorption, and UV-visible spectroscopy. The results reveal that the MBG exhibits the typical ordered characteristics of the hexagonal mesostructure. The system demonstrates great potential in light-sensitive intelligent drug delivery systems and disease therapy fields. PMID:20152945
Lin, H-M; Wang, W-K; Hsiung, P-A; Shyu, S-G
Angiogenic Response to Bioactive Glass Promotes Bone Healing in an Irradiated Calvarial Defect
Localized radiation is an effective treatment modality for carcinomas, yet the associated reduction of the host vasculature significantly inhibits the tissue's regenerative capacity. Low concentrations of bioactive glass (BG) possess angiogenic potential, and we hypothesized that localized BG presentation would increase neovascularization and promote healing in an irradiated bone defect. An isolated calvarial region of Sprague-Dawley rats was irradiated 2 weeks before surgery. Bilateral critical-sized defects were created and immediately filled with a BG-loaded collagen sponge or an empty sponge as an internal control. Histological analysis of calvaria collected after 2 weeks demonstrated greater neovascularization within the defect in the presence of BG than with collagen alone. Noninvasive ultrasound imaging at 4 weeks detected less contrast agent in the brain below BG-treated defects than in the nearby untreated defects and images of treated defects acquired at 2 weeks. The reduced ability to detect contrast agent in BG-treated defects suggested greater attenuation of ultrasound signal due to early bone formation. Micro-computed tomography imaging at 12 weeks demonstrated significantly greater bone volume fraction within BG-treated defects than in controls. These results suggest that neovascularization induced by localized BG delivery promotes bone regeneration in this highly compromised model of bone healing and may offer an alternative approach to costly growth factors and their potential side-effects. PMID:18795867
Leu, Ann; Stieger, Susanne M.; Dayton, Paul; Ferrara, Katherine W.
Hydroxyapatite/SiO(2)-CaO-P(2)O(5) glass materials: in vitro bioactivity and biocompatibility.
Materials obtained by the heat treatment of mixtures of hydroxyapatite (HA) and a silicate-based glass of the system SiO(2)-CaO-P(2)O(5) have been investigated. The influence of the glass content on the porosity, microstructure and on the constituent phases of the final materials was studied. The influence of these factors on the in vitro bioactive behaviour of the obtained materials was also investigated. In addition, an in vitro biocompatibility assay with osteoblastic-like cells was carried out. The addition of the glass to HA induced different solid-state reactions that yield the transformation of HA into alpha- and beta-tricalcium phosphate as well as the formation of silicon-containing phases (silicocarnotite or pseudowollastonite). In these mixtures an enhancement in the porosity, pore size and a heterogeneous microstructure was observed, compared with the precursors. As the sol gel glass content increased, the previous effects were higher. The materials showed the formation of an apatite-like layer on their surface when soaked in simulated body fluid, being faster in the sample with a higher content of glass. The formation of the new layer began in preferential zones in both samples, depending on the different reactivity of the crystalline phases formed. A synergistic effect between HA and glass was observed, showing in the mixtures a faster bioactive behaviour than in HA and glass themselves. The obtained materials allow a good attachment, spread and proliferation of the osteoblastic-like cells and no cytotoxic effect was observed. PMID:16701892
Padilla, S; Romßn, J; Sßnchez-Salcedo, S; Vallet-RegĒ, M
Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting timeĀ=Ā5.8Ā▒Ā0.6Āmin; compressive strengthĀ=Ā25.6Ā▒Ā0.3ĀMPa) released vancomycin over ~25Ādays in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8Āweeks. Osteomyelitis was cured in 87Ā% of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71Ā% for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection. PMID:24477872
Cui, Xu; Zhao, Cunju; Gu, Yifei; Li, Le; Wang, Hui; Huang, Wenhai; Zhou, Nai; Wang, Deping; Zhu, Yi; Xu, Jun; Luo, Shihua; Zhang, Changqing; Rahaman, Mohamed N
In this study, modifications of glass ionomer cements (GICs) were made by adding bioactive glass (BAG) to GIC to obtain bioactive restorative materials. This study used SEM, EDS and visual analysis to examine the bioactivity and the ability of the study materials to mineralize dentin. Conventional cure and resin-modified light-curing GIC were used. The materials consisted of powder and liquid. Three experimental materials were made by mixing 10-30 wt% of BAG powder with GIC powders. Commercially available GIC without BAG were used as controls. Class III restorations were made in altogether 62 intact beagle dog teeth, and the operation was performed under general anesthesia. The restorations were followed clinically for 1, 3 or 6 weeks. Resin-modified GIC containing BAG showed uniform CaP surface formation on the restorations. Mineral depositions in the close vicinity of the restoration-dentin interface and in deeper parts of dentin tubules were also noticed in resin-modified GIC containing BAG particles. It can be concluded that resin-modified GIC containing BAG have good potential in clinical applications where enhanced mineralization is expected. PMID:15958240
Yli-Urpo, Helena; Nõrhi, Matti; Nõrhi, Timo
Thermal Characterizations of silver-containing bioactive glass-coated Sutures.
This study utilized and compared a number of thermal analysis methods to characterize the thermal properties of commercial sutures with and without antimicrobial coatings of silver-doped bioactive glass (AgBG) interlocking particulates. The effect of a slurry dipping technique used to coat resorbable Vicryl (polyglactin 910) and non-resorbable Mersilk surgical sutures with AgBG was investigated using conventional differential scanning calorimetry (DSC), high speed calorimetry (or HYPERDSC), and modulated temperature DSC (MTDSC). These methods were compared in terms of their ability to resolve the thermal transitions of the types of suture materials. Differential thermal analysis (DTA) and thermogravimetric analysis (TGA) were used to verify the thermal degradation temperatures of these materials and to quantify the AgBG coatings on the sutures. The use of complementary thermal analysis techniques enabled the understanding of the effect of the AgBG coating technique on the morphological properties of the sutures. The slurry dipping technique had no significant effect on the thermal transitions of both types of materials. The use of high speed calorimetry through DSC offered better resolution for the transitions that appeared to be weak through conventional heating regimes, and was able to separate broad double transitions. Furthermore, it was shown not to compromise either the melting temperature or the enthalpy of melting. Therefore this method allows for the accurate determination of thermal transitions through much shorter experimental times thus allowing for an increased sample throughput. The combined DTA and TGA indicated that a greater AgBG coating was obtained in the case of the Mersilk sutures. PMID:15972365
Blaker, Jonny J; Boccaccini, Aldo R; Nazhat, Showan N
Morphology and immersion behavior of plasma-sprayed hydroxyapatite/bioactive glass coatings.
A series of hydroxyapatite/bioactive glass (HA/BG) coatings have been plasma-sprayed on Ti6Al-4V substrate using HA/BG powders that were prepared by both sinter-granulation and direct mixing methods. The morphology and immersion behavior of these coatings in a simulated body fluid (SBF) were investigated. The results showed that in-house fabricated BG and sinter-granulated HA powders were irregularly shaped and dense. When 5 wt % or more BG was added in HA, the powder became rough and porous. X-ray diffraction (XRD) patterns showed that the presence of BG enhanced the decomposition of HA structure during fabrication of the powders. Reasonably high bond strengths were obtained from all coatings. The granulated type HA/BG coatings showed no significant differences in bond strength from the mixed type HA/BG coatings. The plasma spray process itself and the presence of BG enhanced the decomposition of apatite. Surface morphology of all sinter-granulated type coatings was similar to that of monolithic HA coating, that was comprised of patches of smooth and shiny glassy film and irregularly-shaped particles on its surface. The dissolution depth of plasma-sprayed coatings immersed in SBF was largely dependent on the type and composition of the coating. Granulated type HA/BG coatings were much less dissolvable than monolithic HA or mixed type HA/BG coatings. It seems that the presently used granulation method for the preparation of HA/BG powders plays a predominant role in determining the dissolution behavior of the plasma-sprayed coatings. PMID:15348047
Ding, S J; Ju, C P; Lin, J H
Background A novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model. Materials and Methods The setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS) cement and for intravenous injection of vancomycin. Results The BG cement had an injectability of >90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18▒2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects. Conclusions These results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured. PMID:24427311
Cui, Xu; Gu, Yi-Fei; Jia, Wei-Tao; Rahaman, Mohamed N.; Wang, Yang; Huang, Wen-Hai; Zhang, Chang-Qing
Bioactive glasses and glass-ceramics of the SiO(2)-CaO-P(2)O(5) system were synthesised by means of a sol-gel method using different phosphorus precursors according to their respective rates of hydrolysis-triethylphosphate (OP(OC(2)H(5))(3)), phosphoric acid (H(3)PO(4)) and a solution prepared by dissolving phosphorus oxide (P(2)O(5)) in ethanol. The resulting materials were characterised by differential scanning calorimetry and thermogravimetry, X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy and by in vitro bioactivity tests in acellular simulated body fluid. The different precursors significantly affected the main steps of the synthesis, beginning with the time required for gel formation. The most striking influence of these precursors was observed during the thermal treatments at 700-1,200 ░C that were used to convert the gels into glasses and glass-ceramics. The samples exhibited very different mineralisation behaviours; especially those prepared using the phosphoric acid, which had a reduced onset temperature of crystallisation and an increased resistance to devitrification. However, all resulting materials were bioactive. The in vitro bioactivity of these materials was strongly affected by the heat treatment temperature. In general, their bioactivity decreased with increasing treatment temperature. For crystallised samples obtained above 900 ░C, the bioactivity was favoured by the presence of two crystalline phases: wollastonite (CaSiO(3)) and tricalcium phosphate (?-Ca(3)(PO(4))(2)). PMID:23114636
Siqueira, Renato Luiz; Zanotto, Edgar Dutra
Poly(lactide-co-glycolide) (PLGA) foams and PLGA\\/titanium dioxide (TiO2) nanoparticle-filled composite foams (porosity>90%) were produced by thermally induced solid¢liquid phase separation (TIPS) and subsequent solvent sublimation. The scaffolds exhibit bimodal and anisotropic pore structures, with tubular macropores (approximately 100?m in diameter) interconnected by a network of micropores. Quasi-static compression testing and dynamic mechanical analysis were carried out and the results were correlated
F. G. Torres; S. N. Nazhat; V. Maquet; A. R. Boccaccini
Silicon is known to have an influence on calcium phosphate deposition and on the differentiation of bone precursor cells. This study explores the effect of the incorporation of silanol (Si-OH) groups into polymeric scaffolds on the osteogenic differentiation of human adipose stem cells (hASC) cultured under dynamic and static conditions. A blend of corn starch with polycaprolactone (30/70 wt.%, SPCL) was used to produce three-dimensional fibre meshes scaffolds by the wet-spinning technique, and a calcium silicate solution was used as a non-solvent to develop an in situ functionalization with Si-OH groups. In vitro assessment, using hASC, of functionalized and non-functionalized scaffolds was evaluated in either ?-MEM or osteogenic medium under static and dynamic conditions (provided by a flow perfusion bioreactor). The functionalized materials, SPCL-Si, exhibit the capacity to sustain cell proliferation and induce their differentiation into the osteogenic lineage. The formation of mineralization nodules was observed in cells cultured on the SPCL-Si materials. Culturing under dynamic conditions using a flow perfusion bioreactor was shown to enhance the hASC proliferation and differentiation and a better distribution of cells within the material. The present work demonstrates the potential of these functionalized materials for future applications in bone tissue engineering. Additionally, these results highlight the simplicity, economic and reliable production process of those materials. PMID:22659174
Rodrigues, A I; Gomes, M E; Leonor, I B; Reis, R L
Osteomyelitis is a disease that is still difficult to treat, with considerable morbidity and associated costs. The current "gold standard" in treatment - debridement and implantation of antibiotic impregnated polymethylmethacrylate (PMMA) beads - presents the disadvantage of a second surgical intervention required for the removal of the beads. We comparatively investigated the in vitro antibacterial effect of S53P4 bioactive glass (BAG) and gentamicin impregnated PMMA beads. Bacterial viability was assessed hourly by Standard Plate Count during 24 hours of incubation, by determining the number of colony forming units (CFU) of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Klebsiella pneumoniae. Both tested materials showed an antibacterial effect on all studied bacteria. In case of S. aureus, BAG granules were almost as effective as gentamicin impregnated PMMA beads, with no statistically significant differences. In contrast, PMMA beads had a superior antibacterial effect on S. epidermidis and K. pneumoniae. The antibacterial effect of BAG was greatly influenced by granule size and contact time. There was a statistically significant correlation between pH values and the number of CFU in the case of S53P4 BAG granules. As a biocompatible and biodegradable bone substitute, S53P4 bioactive glass can be a good alternative in the local management of osteomyelitis. PMID:24939683
Gergely, Istvßn; Zazgyva, Ancuta; Man, Adrian; Zuh, Sßndor Gy÷rgy; Pop, Tudor Sorin
Bioactivity of SiO 2-CaO-P 2O 5-Na 2O glasses containing zinc-iron oxide
NASA Astrophysics Data System (ADS)
Glasses with composition x(ZnO,Fe 2O 3)(65 - x)SiO 220(CaO,P 2O 5)15Na 2O (6 ? x ? 21 mol%) were prepared by melt-quenching technique. Bioactivity of the glasses was investigated in vitro by examining apatite formation on the surface of glasses treated in acellular simulated body fluid (SBF) with ion concentrations nearly equal to those in human blood plasma. Formation of bioactive apatite layer on the samples treated in SBF was confirmed by using Fourier transform infrared reflection (FTIR) spectroscopy, grazing incidence X-ray diffraction (GI-XRD) and scanning electron microscope (SEM) equipped with energy dispersive X-ray spectrometer. Development of an apatite structure on the surface of the SBF treated glass samples as functions of composition and time could be established using the GI-XRD data. FTIR spectra of the glasses treated in SBF show features at characteristic vibration frequencies of apatite after 1-day of immersion in SBF. SEM observations revealed that the spherical particles formed on the glass surface were made of calcium and phosphorus with the Ca/P molar ratio being close to 1.67, corresponding to the value in crystalline apatite. Increase in bioactivity with increasing zinc-iron oxide content was observed. The results have been used to understand the evolution of the apatite surface layer as a function of glass composition and immersion time in SBF.
Singh, Rajendra Kumar; Srinivasan, A.
Microsphere integrated gelatin-siloxane hybrid scaffolds were successfully synthesized by using a combined sol-gel processing,\\u000a post-gelation soaking and freeze-drying process. A bone-like apatite layer was able to form in the Ca2+-containing porous hybrids upon soaking in a simulated body fluid (SBF) up to 1 day. The rate of gentamicin sulfate (GS) release\\u000a from the GS-loaded gelatin-siloxane hybrid microsphere became constant after
Lin Wang; Bing Yu; Li-ping Sun; Lei Ren; Qi-qing Zhang
Macroporous nanowire nanoelectronic scaffolds for synthetic tissues
The development of three-dimensional (3D) synthetic biomaterials as structural and bioactive scaffolds is central to fields ranging from cellular biophysics to regenerative medicine. As of yet, these scaffolds cannot ...
Tian, Bozhi
A new melted bioactive system containing gold nanoparticles (AuNPs) was prepared exploiting a post-synthesis thermal treatment that allows one to modify crystal phases and nature, shape and distribution of the gold species in the glass-ceramic matrix as evidenced by UV¢visible spectroscopy, transmission electron microscopy and powder X-ray diffraction analysis. In human MG-63 osteoblasts the presence of Aun+ species caused an increase of lactate dehydrogenase leakage and malonyldialdehyde production, whereas Hench's Bioglass HAu-600-17 containing only AuNPs did not cause any effect. In addition, HAu-600-17 caused in vitro hydroxyapatite formation and an increase of specific surface area with a controlled release of gold species; this material is then suitable to be used as a model system for the controlled delivery of nanoparticles. PMID:23427096
Aina, Valentina; Cerrato, Giuseppina; Martra, Gianmario; Bergandi, Loredana; Costamagna, Costanzo; Ghigo, Dario; Malavasi, Gianluca; Lusvardi, Gigliola; Menabue, Ledi
One-pot synthesis of macro-mesoporous bioactive glasses/polylactic acid for bone tissue engineering.
The macro-mesoporous bioactive glasses/polylactic acid nanofibers were synthesized via electrospun method followed by acid treatment processing. It was identified to be an effective and simple synthetic strategy to form the uniform nanofibers about 350 nm in size. The non-ionic triblock copolymer, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123), was used as the template for mesoporous structure (5 nm) and the macroporous structure about 10 ?m in size derived from the overlapping of the nanofibers. Furthermore, the surface hydrophilic-hydrophobic property can be adjusted by varying the amount of mesoporous bioglass precursor (MBG-p). With the outstanding structure characters and the suitable hydrophilic property, these nanofiber composites show controlled drug release and the fast hydroxyapatite (HAP) mineralization performance. Herein, the novel materials are expected to have potential application for bone tissue engineering. PMID:25175225
Han, Xiao; Wang, Dan; Chen, Xiang; Lin, Huiming; Qu, Fengyu
The angiogenic capacity of a new biomaterial composite of poly(lactic acid) and calcium phosphate glass (PLA/CaP) was analyzed by noninvasive bioluminescence imaging (BLI) and histological procedures. Human adipose tissue-derived mesenchymal stromal cells expressing cytomegalovirus (CMV) promoter regulated Photinus pyralis luciferase (hAMSC-PLuc) grew up to 30 times the initial cell load, in vitro, when seeded in PLA/CaP scaffolds, but suffered an initial growth crisis followed by recovery when the scaffolds were subcutaneously implanted in SCID mice. To analyze changes in gene expression, hAMSC-PLuc cells were double labeled with a CMV promoter regulated Renilla reniformis luciferase and a Photinus pyralis luciferase reporter regulated by either the PECAM promoter or a hypoxia response element (HRE) artificial promoter and seeded in PLA/CaP and PLA scaffolds implanted in SCID mice. Analysis by BLI showed that hAMSCs in scaffolds were induced to differentiate to the endothelial lineage and did this faster in PLA/CaP than in PLA scaffolds. Endothelial differentiation correlated with a decrease in the activity of HRE regulated luciferase expression, indicative of a reduction of hypoxia. Histological analysis showed that PLA/CaP scaffolds were colonized by a functional host vascular system. Moreover, colonization by isolectin B(4) positive host cells was more effective in PLA/CaP than in PLA scaffolds, corroborating BLI results. PMID:22962041
Vila, Olaia F; Bag¾, Juli R; Navarro, Melba; Alieva, Maria; Aguilar, Elisabeth; Engel, Elisabeth; Planell, Josep; Rubio, Nuria; Blanco, Jer¾nimo
It is demonstrated here that bioactive glasses containing Au nanoparticles (AuNPs) can be selectively functionalized with small molecules carrying either amino or thiol groups by simply varying the temperature and pH of the functionalization batch. The results evidence the following. (i) At room temperature (RT), no functionalization of Au-free glass occurs, whereas in the case of glasses containing AuNPs, stable linkages form only with amino groups, as in this condition Au does not bind with either thiol or hydroxyl groups. The RT functionalization with cysteine and cystine confirms the preferential functionalization through the amino groups, while the -SH groups are oxidized to S-S bridges. (ii) The functionalization with cysteine and cystine, compared at pH = 5, 9, and 12, is shown not to take place at pH = 5 and to be hindered by the glass matrix dissolution at pH = 12 (with consequent release of AuNPs), while the best results are obtained at pH = 9. (iii) For the effect of reaction temperature, at 4 ░C it is possible to obtain a strong Au-S interaction, whereas at RT, a weak Au-N linkage is formed. These results should allow production, in a selective way, of different bonds exhibiting different strengths and, consequently, different release times in solution, with a wide range of possible applications (for instance, weak Au-N bonds in the case of drug delivery, strong Au-S bonds in protein immobilization). PMID:21090664
Aina, Valentina; Marchis, Tatiana; Laurenti, Enzo; Diana, Eliano; Lusvardi, Gigliola; Malavasi, Gianluca; Menabue, Ledi; Cerrato, Giuseppina; Morterra, Claudio
Cellulose-based materials are widely used in analytical chemistry as platforms for chromatographic and immunodiagnostic techniques. Due to its countless advantages (e.g., mechanical properties, three-dimensional structure, large surface to volume area, biocompatibility and biodegradability, and high industrial availability), paper has been rediscovered as a valuable substrate for sensors. Polymeric materials such as cellulosic paper present high protein capture ability, resulting in a large increase of detection signal and improved assay sensitivity. However, cellulose is a rather nonreactive material for direct chemical coupling. Aiming at developing an efficient method for controlled conjugation of cellulose-based materials with proteins, we devised and fabricated a hybrid scaffold based on the adsorption and in situ self-assembly of surface-oxidized Ni nanoparticles on filter paper, which serve as "docking sites" for the selective immobilization of proteins containing polyhistidine tags (His-tag). We demonstrate that the interaction between the nickel substrate and the His-tagged protein G is remarkably resilient toward chemicals at concentrations that quickly disrupt standard Ni-NTA and Ni-IDA complexes, so that this system can be used for applications in which a robust attachment is desired. The bioconjugation with His-tagged protein G allowed the binding of anti-Salmonella antibodies that mediated the immuno-capture of live and motile Salmonella bacteria. The versatility and biocompatibility of the nickel substrate were further demonstrated by enzymatic reactions. PMID:24811229
Bodel¾n, Gustavo; Mourdikoudis, Stefanos; Yate, Luis; Pastoriza-Santos, Isabel; Pķrez-Juste, Jorge; Liz-Marzßn, Luis M
A new surface-coating method by which CaP invert glass is used to improve the bioactivity of titanium alloys has been developed recently. In this method, the powder of CaP invert glass (CaO-P2O5-TiO2-Na2O) is coated on the surface of titanium alloy samples and heated between 1073 and 1123 K. With this treatment, a calcium phosphate layer mainly containing beta-Ca3(PO4)2 phase can be coated easily on titanium alloy samples. In the present study, the effect of this coating process on the fatigue properties of Ti-29Nb-13Ta-4.6Zr, a new metastable beta alloy for biomedical applications, has been investigated. The fatigue endurance limit of the coated alloy was found to be about 15% higher than that of uncoated alloy, as a result of the formation of a hard (alpha + beta) layer and a small amount of the omega phase during the coating process. The coating exhibits excellent adhesion to the substrate during the tensile and fatigue tests. Subsequent ageing at 673 K for 259.2 ks greatly improves the fatigue resistance of the coated alloy due to isothermal omega phase precipitation, and does not have obvious detrimental effect on the coating properties. PMID:15020109
Li, S J; Niinomi, M; Akahori, T; Kasuga, T; Yang, R; Hao, Y L
Background Since the classic Hopkins and Groom druggable genome review in 2002, there have been a number of publications updating both the hypothetical and successful human drug target statistics. However, listings of research targets that define the area between these two extremes are sparse because of the challenges of collating published information at the necessary scale. We have addressed this by interrogating databases, populated by expert curation, of bioactivity data extracted from patents and journal papers over the last 30 years. Results From a subset of just over 27,000 documents we have extracted a set of compound-to-target relationships for biochemical in vitro binding-type assay data for 1,736 human proteins and 1,654 gene identifiers. These are linked to 1,671,951 compound records derived from 823,179 unique chemical structures. The distribution showed a compounds-per-target average of 964 with a maximum of 42,869 (Factor Xa). The list includes non-targets, failed targets and cross-screening targets. The top-278 most actively pursued targets cover 90% of the compounds. We further investigated target ranking by determining the number of molecular frameworks and scaffolds. These were compared to the compound counts as alternative measures of chemical diversity on a per-target basis. Conclusions The compounds-per-protein listing generated in this work (provided as a supplementary file) represents the major proportion of the human drug target landscape defined by published data. We supplemented the simple ranking by the number of compounds assayed with additional rankings by molecular topology. These showed significant differences and provide complementary assessments of chemical tractability. PMID:21569515
3D conductive nanocomposite scaffold for bone tissue engineering.
Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D) ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene) poly(4-styrene sulfonate) (PEDOT:PSS), in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent microscope. Increasing the concentration of the conductive polymer in the scaffold enhanced the cell viability, indicating the improved microstructure of the scaffolds or boosted electrical signaling among cells. These results show that these conductive scaffolds are not only structurally more favorable for bone tissue engineering, but also can be a step forward in combining the tissue engineering techniques with the method of enhancing the bone healing by electrical stimuli. PMID:24399874
Shahini, Aref; Yazdimamaghani, Mostafa; Walker, Kenneth J; Eastman, Margaret A; Hatami-Marbini, Hamed; Smith, Brenda J; Ricci, John L; Madihally, Sundar V; Vashaee, Daryoosh; Tayebi, Lobat
A series of ZrO(2) doped MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) bioactive glass-ceramics were obtained by sintering method. The crystallization behavior, phase composition, morphology and structure of glass-ceramics were characterized. The bending strength, elastic modulus, fracture toughness, micro-hardness and thermal expansion coefficient (TEC) of glass-ceramics were investigated. The in vitro bioactivity and cytotoxicity tests were used to evaluate the bioactivity and biocompatibility of glass-ceramics. The sedimentation mechanism and growth process of apatites on sample surface were discussed. The results showed that the mainly crystalline phases of glass-ceramics were Ca(5)(PO4)3F (fluorapatite) and ?-CaSiO(3). (?-wollastonite). m-ZrO(2) (monoclinic zirconia) declined the crystallization temperatures of glasses. t-ZrO(2) (tetragonal zirconia) increased the crystallization temperature of Ca(5)(PO4)(3)F and declined the crystallization temperature of ?-CaSiO(3). t-ZrO(2) greatly increased the fracture toughness, bending strength and micro-hardness of glass-ceramics. The nanometer apatites were induced on the surface of glass-ceramic after soaking 28 days in SBF (simulated body fluid), indicating the glass-ceramic has good bioactivity. The in vitro cytotoxicity test demonstrated the glass-ceramic has no toxicity to cell. PMID:24780435
Li, H C; Wang, D G; Meng, X G; Chen, C Z
Preparation, structure and bioactivity of xAu 2O 3Ę(100 - x)[P 2O 5ĘCaO] glass system
NASA Astrophysics Data System (ADS)
Gold doped calcium phosphate glasses were prepared by the melting method. The structure of Au 2O 3-P 2O 5-CaO glasses is investigated using X-ray diffraction, infrared absorption and Raman scattering. The depth characterization of their structures is essential for the understanding of the properties of biocompatible materials. Thermal analysis DTA and TGA were also made to study behavior under different temperature regions and to see chemical changes versus time and temperature of these glasses. Bioactivity of the glasses was investigated in vitro by examining apatite formation on the surface of glasses treated in acellular simulated body fluid (SBF) with ion concentrations nearly equal to those in human blood plasma. Formation of bioactive apatite layer on the samples treated in SBF for 28 days at 37 ░C was confirmed by X-ray diffraction (XRD) and scanning electron microscope (SEM). The effect of SBF soaking induces structural changes on the surface, reflected by the appearance of nano-crystalline particles agglomerated into micro-aggregates.
Regos, Adriana N.; Ardelean, I.
Spatial and temporal control of bioactive signals in three-dimensional (3D) tissue engineering scaffolds is greatly desired. Coupled together, these attributes may mimic and maintain complex signal patterns, such as those observed during axonal regeneration or neovascularization. Seamless polymer constructs may provide a route to achieve spatial control of signal distribution. In this study, a novel microparticle-based scaffold fabrication technique is introduced as a method to create 3D scaffolds with spatial control over model dyes using uniform poly(D,L-lactide-co-glycolide) microspheres. Uniform microspheres were produced using the Precision Particle Fabrication technique. Scaffolds were assembled by flowing microsphere suspensions into a cylindrical glass mold, and then microspheres were physically attached to form a continuous scaffold using ethanol treatment. An ethanol soak of 1?h was found to be optimum for improved mechanical characteristics. Morphological and physical characterization of the scaffolds revealed that microsphere matrices were porous (41.1?▒?2.1%) and well connected, and their compressive stiffness ranged from 142 to 306?kPa. Culturing chondrocytes on the scaffolds revealed the compatibility of these substrates with cell attachment and viability. In addition, bilayered, multilayered, and gradient scaffolds were fabricated, exhibiting excellent spatial control and resolution. Such novel scaffolds can serve as sustained delivery devices of heterogeneous signals in a continuous and seamless manner, and may be particularly useful in future interfacial tissue engineering investigations. PMID:18795865
Singh, Milind; Morris, Casey P.; Ellis, Ryan J.; Detamore, Michael S.
This study aimed to evaluate the influence of implant design and bioactive glass (BAG) coating on the response of bone to fiber-reinforced composite (FRC) implants. Three different FRC implant types were manufactured for the study: non-threaded implants with a BAG coating; threaded implants with a BAG coating; and threaded implants with a grit-blasted surface. Thirty-six implants (six implants for each group per time point) were installed in the tibiae of six pigs. After an implantation period of 4 and 12 wk, the implants were retrieved and prepared for micro-computed tomography (micro-CT), push-out testing, and scanning electron microscopy analysis. Micro-CT demonstrated that the screw-threads and implant structure remained undamaged during the installation. The threaded FRC/BAG implants had the highest bone volume after 12 wk of implantation. The push-out strengths of the threaded FRC/BAG implants after 4 and 12 wk (463░N and 676░N, respectively) were significantly higher than those of the threaded FRC implants (416░N and 549░N, respectively) and the nonthreaded FRC/BAG implants (219░N and 430░N, respectively). Statistically significant correlation was found between bone volume and push-out strength values. This study showed that osseointegrated FRC implants can withstand the static loading up to failure without fracture, and that the addition of BAG significantly improves the push-out strength of FRC implants. PMID:24863874
Ballo, Ahmed M; Akca, Eralp; Ozen, Tuncer; Moritz, Niko; Lassila, Lippo; Vallittu, Pekka; Nõrhi, Timo
Platelet-rich plasma plus bioactive glass in the treatment of intra-bony defects: a study in dogs
Objective This study was designed to evaluate, histomorphometrically, the association of platelet-rich plasma (PRP) and bioactive glass (BG) in the treatment of periodontal intrabony defects. Material and Methods Nine mongrel dogs were included in the study. Three-wall intrabony defects were surgically created at the mesial and distal aspect of first mandibular molar and exposed to plaque accumulation for 1 month. The defects were randomly assigned to the groups: control, BG, PRP, PRP+BG. Dogs were sacrificed 90 days after the surgeries. The histometric parameters evaluated were: length of sulcular and junctional epithelium, connective tissue adaptation, new cementum, new bone, defect extension and area of new bone filling the defect. Results A superior area of new bone was observed in PRP+BG and BG (13.80▒2.32 mm2 and 15.63▒2.64 mm2, respectively) when compared to the other groups (8.19▒1.46 mm2 and 8.81▒1.47 mm2 for control and PRP, respectively). No statistically significant differences were observed in the remaining parameters. Conclusion Within the limits of this study, it may be concluded that PRP failed to provide statistically significant improvements in the histometric parameters. PMID:21437475
CARVALHO, Marcelo Diniz; SUAID, FabrĒcia Ferreira; SANTAMARIA, Mauro Pedrine; CASATI, Marcio Zaffalon; NOCITI Jr., Francisco Humberto; SALLUM, Antonio Wilson; SALLUM, Enilson Ant¶nio
Background: In periodontal regeneration, several alloplastic materials are being used with a goal to reconstruct new osseous tissue in the infrabony defect sites. The present study was undertaken to evaluate the efficacy of hydroxyapatite¢bioactive glass (HA:BG) composite granules in the management of periodontal bony defects. Materials and Methods: A randomized control study was conducted. Subjects with infrabony defects were divided into three groups. Test Group 1 (n = 10): Defect site was treated with HA:BG, with a biodegradable membrane. Test Group 2 (n = 10): Defect site was treated with HAP, with a biodegradable membrane. Control group (n = 10): Defect site was treated with open flap debridement with a biodegradable membrane Results: The healing of defects was uneventful and free of any biological complications. The gain in clinical attachment level, reduction of probing pocket depth, and defect fill were statistically significant in all three groups. TG1 sites showed significant defect fill than TG2 and CG sites. Conclusion: The performance of HA:BG was better compared to HAP and open flap debridement for the reconstruction of infrabony defects.
Debnath, Tirthankar; Chakraborty, Abhijit; Pal, Tamal Kanti
Antibacterial and bioactive silver-containing Na2O x CaO x 2SiO2 glass prepared by sol-gel method.
The antibacterial effect of addition of silver oxide to Na2O x CaO x 2SiO2 glass have been studied. Silver containing and silver free Na2O x CaO x 2SiO2 glasses have been prepared by sol-gel synthesis using tetramethil orthosilicate, sodium ethoxide, calcium nitrate tetrahydrate and silver nitrate as starting materials and methyl ethyl ketone as solvent. The gel was examined by differential thermal analysis, thermo gravimetric analysis, FTIR spectroscopy and X-ray diffraction analysis. Antibacterial and bioactive tests on gel glass powders, obtained after a heat treatment of 2 h at 600 degrees C of the dried gel, were carried out. High antimicrobial effects of samples against Escherichia coli and Streptococcus mutans were found. FTIR measurements and SEM micrographs have ascertained the formation of a hydroxyapatite layer on the surface of samples soaked in a simulated body fluid for different times. PMID:15387420
Catauro, M; Raucci, M G; De Gaetano, F; Marotta, A
Bioactive glasses (BAGs) are being investigated for the repair and reconstruction of bone defects, as they exhibit osteoconductive and osteostimulatory potential. However, successful bone regeneration requires also the neovascularization of the construct which is, among other factors, guided by vascular endothelial growth factor (VEGF). In this study, BAG S53P4 (53% SiO2 , 23% Na2 O, 20% CaO, 4% P2 O5 ) is investigated in relation to VEGF-release and response of fibroblast cells. Human CD-18CO fibroblasts were cultivated in contact with different granules of different sizes (0.5-0.8 mm, 1.0-2.0 mm, and 2.0-3.15 mm) and at different concentrations (0-1 wt/vol % of BAG) for 72 h. The analysis of morphology revealed no toxic effect for all granule sizes and concentrations. Compared with the reference, lactate dehydrogenase-activity of CCD-18CO cells increased in contact with BAG samples. The VEGF release from CCD-18CO fibroblasts cultured on different granule sizes and at different concentrations after 72 h of incubation was quantified. It was found that particles of 0.5-0.8 mm and 1.0-2.0 mm in size enhanced VEGF release, whereas BAG particle sizes of 2.0-3.15 mm led to inhibition of VEGF release. The results are relevant to understand the influence of the particle size and concentration of BAG S53P4 on VEGF expression and neovascularization. ® 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4055-4061, 2014. PMID:24357515
Detsch, Rainer; Stoor, Patricia; Gr³newald, Alina; Roether, Judith A; Lindfors, Nina C; Boccaccini, Aldo R
The aim of this study was to investigate the ability of mesoporous bioactive glass with ordered nanopores (80S MBG) to adsorb and provide the delayed release of 125I-tagged bone morphogenetic protein-2 (BMP-2). A 50 mg piece of 80S MBG was produced, which comprised SiO2, CaO and P2O5 in a component molar ratio of 80:15:5. Each MBG piece adsorbed 30 ?g 125I-BMP-2. Persistent radioactivity in the MBG was periodically measured in simulated body fluid. The total amount of BMP-2 released and the mean amount released per day were calculated. A delayed release curve of BMP-2 was constructed. SPSS 15.0 software was used to perform a statistical analysis. The amount of BMP-2 released in the first two days was one-quarter of the total load. A line equation, y = 490.55ū1/2 + 7268.82, was obtained from the square root of protein release doses value at 3¢94 days. The total amount of BMP-2 released over 94 days was 11.894 ?g, which was ~39.6% of the total load. The half-life of the release time was 248 days. From the second week, the rate of BMP release had stabilized to a mean of 37.42▒18.67 ng/day and the difference of the mean amount released per day had no statistical significance (P>0.05). High adsorption and delayed release effects of BMP-2 were observed in 80S MBG. The delayed release conforms to the Higuchi equation, which indicates possible applications in promoting bone healing. PMID:24250724
Bioceramics, such as silica-based glasses, are widely used in bone and teeth restoration. Nowadays, the association between nanotechnology and pharmacology is one of the most promising research fields in cancer therapy. The advanced processing methods and new chemical strategies allow the incorporation of drugs within them or on their functionalized surfaces. Bioceramics can act as local drug delivery systems to treat bone and teeth diseases. The present paper reports data related to the development of a pH-stimuli responsive bioactive glass. The glass conjugation with 5-aminofluorescein (5-AF), through a pH-sensitive organic spacer, allows to produce a pH-responsive bioactive biomaterial: when it is exposed to specific pH changes, it can favour the release of 5-AF directly at the target site. 5-AF has been chosen as a simple, low cost, non toxic model to simulate doxorubicin, an anticancer drug. As doxorubicin, 5-AF contains an amino group in its structure in order to form an amide bond with the carboxylic functionalities of the glass. Raman spectroscopy and thermal analysis confirm the glass conjugation of 5-AF by means of an amide bond; the amount of 5-AF loaded was very high (?65 and 44Āwt%). The release tests at two different pH (4.2 and 7.4) show that the amount of released 5-AF is higher at acid pH with respect to physiological one. This preliminary datum evidenced that a pH-sensitive drug delivery system has been developed. The low amount of 5-AF released (<1Āwt% of the total 5-AF) is due to the very low solubility of 5-AF in aqueous medium. This disadvantage, may be overcome in a dynamic environment (physiological conditions), where it is possible to obtain a drug release system ensuring an effective therapeutic dose for long times and, at the same time, avoiding the drug toxicity. PMID:24722810
Aina, Valentina; Malavasi, Gianluca; Magistris, Claudio; Cerrato, Giuseppina; Martra, Gianmario; Viscardi, Guido; Menabue, Ledi; Lusvardi, Gigliola
Implants formed of metals, bioceramics, or polymers may provide an alternative to autografts for treating large bone defects. However, limitations to each material motivate the examination of composites to capitalize on the beneficial aspects of individual components and to address the need for conferring bioactive behavior to the polymer matrix. We hypothesized that the inclusion of different bioceramics in a ceramic-polymer composite would alter the physical properties of the implant and the cellular osteogenic response. To test this, composite scaffolds formed from poly(lactide-co-glycolide) (PLG) and either hydroxyapatite (HA), ?-tricalcium phosphate (TCP), or bioactive glass (Bioglass 45S«, BG) were fabricated, and the physical properties of each scaffold were examined. We quantified cell proliferation by DNA content, osteogenic response of human osteoblasts (NHOsts) to composite scaffolds by alkaline phosphatase (ALP) activity, and changes in gene expression by qPCR. Compared to BG-PLG scaffolds, HA-PLG and TCP-PLG composite scaffolds possessed greater compressive moduli. NHOsts on BG-PLG substrates exhibited higher ALP activity than those on control, HA-, or TCP-PLG scaffolds after 21 days, and cells on composites exhibited a 3-fold increase in ALP activity between 7 and 21 days versus a minimal increase on control scaffolds. Compared to cells on PLG controls, RUNX2 expression in NHOsts on composite scaffolds was lower at both 7 and 21 days, while expression of genes encoding for bone matrix proteins (COL1A1 and SPARC) was higher on BG-PLG scaffolds at both time points. These data demonstrate the importance of selecting a ceramic when fabricating composites applied for bone healing. PMID:24955539
Morales-Hernandez, Diana G.; Genetos, Damian C.; Working, David M.; Murphy, Kaitlin C.; Leach, J. Kent
This is the first reported study to prepare highly porous baghdadite (Ca?ZrSi?O?) scaffolds with and without surface modification and investigate their ability to repair critical-sized bone defects in a rabbit radius under normal load. The modification was carried out to improve the mechanical properties of the baghdadite scaffolds (particularly to address their brittleness) by coating their surfaces with a thin layer (?400 nm) of polycaprolactone (PCL)/bioactive glass nanoparticles (nBGs). The ?-tricalcium phosphate/hydroxyapatite (TCP/HA) scaffolds with and without modification were used as the control groups. All of the tested scaffolds had an open and interconnected porous structure with a porosity of ?85% and average pore size of 500 ?m. The scaffolds (six per scaffold type and size of 4 mm ū 4 mm ū 15 mm) were implanted (press-fit) into the rabbit radial segmental defects for 12 weeks. Micro-computed tomography and histological evaluations were used to determine bone ingrowth, bone quality, and implant integration after 12 weeks of healing. Extensive new bone formation with complete bridging of the radial defect was evident with the baghdadite scaffolds (modified/unmodified) at the periphery and in close proximity to the ceramics within the pores, in contrast to TCP/HA scaffolds (modified/unmodified), where bone tended to grow between the ulna adjacent to the implant edge. Although the modification of the baghdadite scaffolds significantly improved their mechanical properties, it did not show any significant effect on in vivo bone formation. Our findings suggest that baghdadite scaffolds with and without modification can serve as a potential material to repair critical sized bone defects. PMID:22842031
Roohani-Esfahani, S I; Dunstan, C R; Davies, B; Pearce, S; Williams, R; Zreiqat, H
The combination of thick glass coatings that can protect Ti6Al4V from corrosion in the body fluids, and mesoporous silica films able to readily induce the formation of apatite when immersed in a simulated body fluid (SBF), has been investigated in this work as a possible route towards more resistant and long-lasting implants. Glasses in the system Si-Ca-Mg-Na-K-P-O with thermal expansion coefficients close to that of Ti6Al4V were prepared and used to coat this alloy by an enameling technique. However, the glasses apt to coat Ti6Al4V exhibited a very limited capacity to induce apatite formation in SBF. In order to enhance their bioactivity, a thin film of mesoporous silica was applied on the exterior of the specimens by spin coating a sol-gel solution. When tested in SBF, these coatings induced apatite formation after 7 days. The mesoporosity of the silica film was created through a triblock-copolymer-templating process. The diameters of the mesochannels could be adjusted by changing the size of the directing agent. A preferred alignment of the mesostructure was observed. The removal of the organic templates could be achieved through a photocalcination treatment, which, compared to conventional thermocalcination, offered several advantages. PMID:11372056
Gomez-Vega, J M; Hozumi, A; Saiz, E; Tomsia, A P; Sugimura, H; Takai, O
NASA Astrophysics Data System (ADS)
Classical and ab initio molecular dynamics (MD) simulations have been carried out to investigate the effect of a different treatment of interatomic forces in modeling the structural properties of multicomponent glasses and melts. The simulated system is a soda-lime phosphosilicate composition with bioactive properties. Because the bioactivity of these materials depends on their medium-range structural features, such as the network connectivity and the Qn distribution (where Qn is a tetrahedral species bonded to n bridging oxygens) of silicon and phosphorus network formers, it is essential to assess whether, and up to what extent, classical potentials can reproduce these properties. The results indicate that the inclusion of the oxide ion polarization through a shell-model (SM) approach provides a more accurate representation of the medium-range structure compared to rigid-ion (RI) potentials. Insight into the causes of these improvements has been obtained by comparing the melt-and-quench transformation of a small sample of the same system, modeled using Car-Parrinello MD (CPMD), to the classical MD runs with SM and RI potentials. Both classical potentials show some limitations in reproducing the highly distorted structure of the melt denoted by the CPMD runs; however, the inclusion of polarization in the SM potential results in a better and qualitatively correct dynamical balance between the interconversion of Qn species during the cooling of the melt. This effect seems to reflect the slower decay of the fraction of structural defects during the cooling with the SM potential. Because these transient defects have a central role in mediating the Qn transformations, as previously proposed and confirmed by the current simulations, their presence in the melt is essential to produce an accurate final distribution of Qn species in the glass.
Tilocca, Antonio
Current clinical therapies for traumatic or chronic injuries involving osteochondral tissue result in temporary pain reduction and filling of the defect but with biomechanically inferior repair tissue. Tissue engineering of osteochondral repair tissue using autologous cells and bioactive biomaterials has the potential to overcome the current limitations and results in native-like repair tissue with good integration capabilities. For this reason, we applied two modem biomaterial design techniques, namely, electrospinning and fused deposition modeling (FDM), to produce bioactive poly(epsilon-caprolactone)/collagen (PCL/Col) type I and type II-PCL-tri-calcium phosphate (TCP)/Col composites for precursor cell-based osteochondral repair. The application of these two design techniques (electrospinning and FDM) allowed us to specifically produce the a suitable three-dimensional (3D) environment for the cells to grow into a particular tissue (cartilage and bone) in vitro prior to in vivo implantation. We hypothesize that our new designed biomaterials, seeded with autologous bone marrow-derived precursor cells, in combination with bioreactor-stimulated cell-culture techniques can be used to produce clinically relevant osteochondral repair tissue. PMID:18085205
Schumann, Detlef; Ekaputra, Andrew K; Lam, Christopher X F; Hutmacher, Dietmar W
Highlights: Black-Right-Pointing-Pointer Bioactive glass-ceramic coatings for bone tissue repair and regeneration. Black-Right-Pointing-Pointer Pulsed Lased Deposition allowed congruent transfer of target composition to coating. Black-Right-Pointing-Pointer Target was prepared by sol-gel process suitable for compositional tailoring. Black-Right-Pointing-Pointer Titanium, widely used for orthopaedics and dental implants, was used as substrate. Black-Right-Pointing-Pointer The physico-chemical properties of the prepared coatings are reported. -- Abstract: The deposition of innovative glass-ceramic composition (i.e. RKKP) coatings by Pulsed Lased Deposition (PLD) technique is reported. RKKP was synthesised following two methodologies: melt-processing and sol-gel, the latter being particularly suitable to tailor the compositional range. The PLD advantage with respect to other deposition techniques is the congruent transfer of the target composition to the coating. The physico-chemical properties of films were investigated by Scanning Electron and Atomic Force Microscopies, Fourier Transform Infrared Spectroscopy, Angular and Energy Dispersive X-ray Diffraction, and Vickers microhardness. The deposition performed at 12 J/cm{sup 2} and 500 Degree-Sign C allows to prepare crystalline films with the composition that replicates rather well that of the initial targets. The 0.6 {mu}m thin melt-processing RKKP films, possessing the hardness of 25 GPa, and the 4.3 {mu}m thick sol-gel films with the hardness of 17 GPa were obtained.
Rau, J.V., E-mail: firstname.lastname@example.com [Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche, Via del Fosso del Cavaliere, 100-00133 Rome (Italy); Teghil, R. [Universita della Basilicata, Dipartimento di Chimica 'A.M. Tamburro', Via dell'Ateneo Lucano, 10-85100 Potenza (Italy) [Universita della Basilicata, Dipartimento di Chimica 'A.M. Tamburro', Via dell'Ateneo Lucano, 10-85100 Potenza (Italy); CNR-IMIP U.O.S. di Potenza, Zona Industriale di Tito scalo (PZ) (Italy); Fosca, M. [Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche, Via del Fosso del Cavaliere, 100-00133 Rome (Italy) [Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche, Via del Fosso del Cavaliere, 100-00133 Rome (Italy); Universita di Roma 'La Sapienza', Dipartimento di Chimica, Piazzale Aldo Moro, 5-00185 Rome (Italy); De Bonis, A. [Universita della Basilicata, Dipartimento di Chimica 'A.M. Tamburro', Via dell'Ateneo Lucano, 10-85100 Potenza (Italy) [Universita della Basilicata, Dipartimento di Chimica 'A.M. Tamburro', Via dell'Ateneo Lucano, 10-85100 Potenza (Italy); CNR-IMIP U.O.S. di Potenza, Zona Industriale di Tito scalo (PZ) (Italy); Cacciotti, I.; Bianco, A. [Universita di Roma 'Tor Vergata', Dipartimento di Ingegneria Industriale, UR INSTM 'Roma Tor Vergata', Via del Politecnico, 1-00133 Rome (Italy)] [Universita di Roma 'Tor Vergata', Dipartimento di Ingegneria Industriale, UR INSTM 'Roma Tor Vergata', Via del Politecnico, 1-00133 Rome (Italy); Albertini, V. Rossi [Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche, Via del Fosso del Cavaliere, 100-00133 Rome (Italy)] [Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche, Via del Fosso del Cavaliere, 100-00133 Rome (Italy); Caminiti, R. [Universita di Roma 'La Sapienza', Dipartimento di Chimica, Piazzale Aldo Moro, 5-00185 Rome (Italy)] [Universita di Roma 'La Sapienza', Dipartimento di Chimica, Piazzale Aldo Moro, 5-00185 Rome (Italy); Ravaglioli, A. [Parco Torricelli delle Arti e delle Scienze, Via Granarolo, 64-48018 Faenza (Ra) (Italy)] [Parco Torricelli delle Arti e delle Scienze, Via Granarolo, 64-48018 Faenza (Ra) (Italy)
Recent advances in bone tissue engineering scaffolds
Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, biodegradable materials that harbor different growth factors, drugs, genes or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved. PMID:22939815
Bose, Susmita; Roy, Mangal; Bandyopadhyay, Amit
By exploiting 1H and 31P magic-angle spinning nuclear magnetic resonance (NMR) spectroscopy, we explore the proton and orthophosphate environments in biomimetic amorphous calcium phosphate (ACP) and hydroxy-apatite (HA), as grown in vitro at the surface of a 10CaO¢85SiO2¢5P2O5 mesoporous bioactive glass (MBG) in either a simulated body fluid or buffered water. Transmission electron microscopy confirmed the presence of a calcium phosphate layer comprising nanocrystalline HA. Two-dimensional 1H¢31P heteronuclear correlation NMR established predominantly 1H2O?31PO43¢ and O1H?31PO43¢ contacts in the amorphous and crystalline component, respectively, of the MBG surface-layer; these two pairs exhibit distinctly different 1H?31P cross-polarization dynamics, revealing a twice as large squared effective 1H¢31P dipolar coupling constant in ACP compared with HA. These respective observations are mirrored in synthetic (well-crystalline) HA, and the amorphous calcium orthophosphate (CaP) clusters that are present in the pristine MBG pore walls: besides highlighting very similar local 1H and 31P environments in synthetic and biomimetic HA, our findings evidence closely related NMR characteristics, and thereby similar local structures, of the CaP clusters in the pristine MBG relative to biomimetic ACP. PMID:22132242
Novel Antibacterial Nanofibrous PLLA Scaffolds
In order to achieve high local bioactivity and low systemic side effects of antibiotics in the treatment of dental, periodontal and bone infections, a localized and temporally controlled delivery system is crucial. In this study, a three-dimensional (3D) porous tissue engineering scaffold was developed with the ability to release antibiotics in a controlled fashion for long-term inhibition of bacterial growth. The highly soluble antibiotic drug, Doxycycline (DOXY), was successfully incorporated into PLGA nanospheres using a modified water-in-oil-in-oil (w/o/o) emulsion method. The PLGA nanospheres (NS) were then incorporated into prefabricated nanofibrous PLLA scaffolds with a well interconnected macroporous structure. The release kinetics of DOXY from four different PLGA NS formulations on a PLLA scaffold was investigated. DOXY could be released from the NS-scaffolds in a locally and temporally controlled manner. The DOXY release is controlled by DOXY diffusion out of the NS and is strongly dependent upon the physical and chemical properties of the PLGA. While PLGA50-6.5K, PLGA50-64K, and PLGA75-113K NS-scaffolds discharge DOXY rapidly with a high initial burst release, PLGA85-142K NS-scaffold can extend the release of DOXY to longer than 6 weeks with a low initial burst release. Compared to NS alone, the NS incorporated on a 3-D scaffold had significantly reduced the initial burst release. In vitro antibacterial tests of PLGA85 NS-scaffold demonstrated its ability to inhibit common bacterial growth (S.aureus and E.coli) for a prolonged duration. The successful incorporation of DOXY onto 3-D scaffolds and its controlled release from scaffolds extends the usage of nano-fibrous scaffolds from the delivery of large molecules such as growth factors to the delivery of small hydrophilic drugs, allowing for a broader application and a more complex tissue engineering strategy. PMID:20570700
Feng, Kai; Sun, Hongli; Bradley, Mark A.; Dupler, Ellen J.; Giannobile, William V.; Ma, Peter X.
NASA Astrophysics Data System (ADS)
Bioactive materials chemically bond to tissues through the development of biologically active apatite. Porous structures in biomaterials are designed to enhance bioactivity, grow artificial tissues and achieve better integration with host tissues in the body. The goal of this research is to design, fabricate and characterize novel porous bioactive materials. 3D ordered macroporous bioactive glasses (3DOM-BGs, pore size: 200--1000 nm) were prepared using a sol-gel process and colloidal crystal templates. 3DOM-BGs are more bioactive and degradable than mesoporous (pore size <50 nm) sol-gel BGs in simulated body fluid (SBF). Apatite formation and 3DOM-BG degradation rates increased with the decrease of soaking ratio. Apatite induction time in SBF increased with 3DOM-BG calcination temperature (600--800░C). Apatite formation and 3DOMBG degradation were slightly enhanced for a phosphate containing composition. Large 3DOM-BG particles formed less apatite and degraded less completely as compared with small particles. An increase in macropore size slowed down 3DOM-BG degradation and apatite formation processes. After heating the converted apatite at a temperature higher than 700░C, highly crystalline hydroxyapatite and a minor tri-calcium phosphate phase formed. 3DOM-BGs have potential applications as bone/periodontal fillers, and drugs and biological factors delivery agents. Anchoring artificial soft tissues (e.g., cartilage) to native bone presents a challenge. Porous polymer/bioactive glass composites are candidate materials for engineering artificial soft tissue/bone interfaces. Porous composites consisting of polymer matrices (e.g., polysulfone, polylactide, and polyurethane) and bioactive glass particles were prepared by polymer phase separation techniques adapted to include ceramic particles. Composites (thickness: 200--500 mum) have asymmetric structures with dense top layers and porous structures beneath. Porous structures consist of large pores (>100 mum) in a network of smaller (<10 mum) interconnected pores. Dense layers can be removed and large pores exposed by abrasion or salt leaching techniques. Composite modulus was enhanced with the increase of glass content, due to the change in composition and pore content. The growth of bone-like apatite on and inside composites after soaking in SBF demonstrated their potential for integration with bone. Cell culture studies revealed that composite surfaces were suitable for attachment, spreading and proliferation of chondrocytes.
Zhang, Kai
Nanotechnology Biomimetic Cartilage Regenerative Scaffolds
Cartilage has a limited regenerative capacity. Faced with the clinical challenge of reconstruction of cartilage defects, the field of cartilage engineering has evolved. This article reviews current concepts and strategies in cartilage engineering with an emphasis on the application of nanotechnology in the production of biomimetic cartilage regenerative scaffolds. The structural architecture and composition of the cartilage extracellular matrix and the evolution of tissue engineering concepts and scaffold technology over the last two decades are outlined. Current advances in biomimetic techniques to produce nanoscaled fibrous scaffolds, together with innovative methods to improve scaffold biofunctionality with bioactive cues are highlighted. To date, the majority of research into cartilage regeneration has been focused on articular cartilage due to the high prevalence of large joint osteoarthritis in an increasingly aging population. Nevertheless, the principles and advances are applicable to cartilage engineering for plastic and reconstructive surgery. PMID:24883273
Sardinha, Jose Paulo; Myers, Simon
Bioglass has been used for bone-filling material in bone tissue engineering, but its lean mechanical strength limits its applications in load-bearing positions. Carbon nanotubes (CNTs), with their high aspect ratio and excellent mechanical properties, have the potential to strengthen and toughen bioactive glass material without offsetting its bioactivity. Therefore, in this research, multiwall carbon nanotube (MWCNT)/45S5 Bioglass composite scaffolds have been successfully prepared by means of freeze casting process. 45S5 Bioglass was synthesized by the sol-gel processing method. The obtained material was characterized with X-ray powder diffraction (XRD). The mechanical properties of the scaffolds, such as compression strength and elastic modulus, were measured. Finally, compared with the scaffolds prepared by 100% 45S5 Bioglass powders, the addition of 0.25?wt.% MWCNTs increases the compressive strength and elastic modulus of 45S5 Bioglass scaffolds from 2.08 to 4.56?MPa (a 119% increase) and 111.50 to 266.59?MPa (a 139% increase), respectively. PMID:24294609
Touri, R.; Moztarzadeh, F.; Sadeghian, Z.; Bizari, D.; Tahriri, M.; Mozafari, M.
Bioactivity-guided mapping and navigation of chemical space
The structure- and chemistry-based hierarchical organization of library scaffolds in tree-like arrangements provides a valid, intuitive means to map and navigate chemical space. We demonstrate that scaffold trees built using bioactivity as the key selection criterion for structural simplification during tree construction allow efficient and intuitive mapping, visualization and navigation of the chemical space defined by a given library, which
Steffen Renner; Willem A L van Otterlo; Marta Dominguez Seoane; Sabine M÷cklinghoff; Bettina Hofmann; Stefan Wetzel; Ansgar Schuffenhauer; Peter Ertl; Tudor I Oprea; Dieter Steinhilber; Luc Brunsveld; Daniel Rauh; Herbert Waldmann
Surface transformations of Bioglass 45S5 during scaffold synthesis for bone tissue engineering.
In physiological fluid, a layer of hydroxycarbonate apatite, similar to bone mineral, develops on the surface of Bioglass 45S5. Collagen from the surrounding tissue is adsorbed on this layer that attracts osteoblasts, and favors bone regrowth. Bioglass is therefore an osteoinductive material. Still, due to its brittleness, the glass alone cannot be used to heal large bone defects. To overcome this issue, Bioglass is used to form a composite scaffold with poly(D,L-lactide) (PDLLA), a biodegradable polymer. The goal of this work is to understand Bioglass reactivity throughout scaffold fabrication via a low-temperature route, the solvent casting and particulate leaching technique. Changes in Bioglass (especially its surface) are susceptible to occur both while in contact with the processing fluids and potentially through a reaction with the surrounding polymeric matrix. Here we analyzed the surface changes of three different Bioglass samples: (i) as-received, (ii) treated in solutions that parallel those used in scaffold fabrication, and (iii) extracted from the scaffolds. We showed that extracted, just like treated, Bioglass deviates from the as-received, but to a larger extent. X-ray photoelectron and infrared spectroscopy support the theory that Bioglass surface was modified not just through contact with the solutions in scaffold fabrication, but upon an interaction with the polymeric matrix. The polymer network slows down the Na(+)/H(+) exchange between Bioglass and water used to leach salt particles to create pores within the scaffold. Changes in surface properties affect the bioactivity of Bioglass and thus of the composite scaffolds, and are therefore critical to identify. PMID:23305513
Abdollahi, Sara; Ma, Alvin Chih Chien; Cerruti, Marta
Inorganic-Organic Hydrogel Scaffolds for Tissue Engineering
) and chemical properties (e.g. hydrophobicity, hydration and bioactivity). Notably, recent studies suggest that scaffold properties (e.g. modulus) may be as potent as growth factors in terms of directing stem cell fate. Thus, 3D scaffolds possessing specific...
Bailey, Brennan
Accepted Manuscript Title: Thermal investigations of Ti and Ag-doped bioactive
Accepted Manuscript Title: Thermal investigations of Ti and Ag-doped bioactive glasses Author: EB. LefeuvreB. BureauO. Merdrignac- Conanec Thermal investigations of Ti and Ag-doped bioactive glasses (2014.tca.2014.02.001 #12;Page 1 of 20 Accepted M anuscript Thermal investigations of Ti and Ag-doped bioactive
Paris-Sud XI, Universit├® de
Glasses in the system xB2O3(1?x) [yCaOP2O5], (x=0, 0.1, 0.2, 0.3, y=2, 2.6, 3, 4, 5) have been prepared by fast quenching of high temperature melts. The presence of B2O3 affected the glass forming ability, allowing the preparation of calcium phosphate glasses with y?2.6. The structure of glasses was analyzed by ?-Raman and infrared spectroscopy. The analysis indicated that the glass
A. Saranti; I. Koutselas; M. A. Karakassides
This study aims to develop glass ceramics in the calcium phosphate system that exhibit suitable properties to be used for biomedical applications. Calcium phosphate glasses with the incorporation of small additions of MgO and TiO2 oxides were prepared in the pyro-and orthophosphate regions. The glass ceramics were prepared by a controlled powder sintering process through heat-treatment at different temperatures, as
A. G. Dias; J. M. S. Skakle; I. R. Gibson; M. A. Lopes; J. D. Santos
Improved cell activity on biodegradable photopolymer scaffolds using titanate nanotube coatings.
The development of bioactive materials is in the premise of tissue engineering. For several years, surface functionalization of scaffolds has been one of the most promising approaches to stimulate cellular activity and finally improve implant success. Herein, we describe the development of a bioactive composite scaffold composed of a biodegradable photopolymer scaffold and titanate nanotubes (TNTs). The biodegradable photopolymer scaffolds were fabricated by applying mask-projection excimer laser photocuring at 308nm. TNTs were synthesized and then spin-coated on the porous scaffolds. Upon culturing fibroblast cells on scaffolds, we found that nanotubes coating affects cell viability and proliferation demonstrating that TNT coatings enhance cell growth on the scaffolds by further improving their surface topography. PMID:25280677
Beke, S; Barenghi, R; Farkas, B; Romano, I; K?r÷si, L; Scaglione, S; Brandi, F
Synthetic materials can be electrospun into submicron or nanofibrous scaffolds to mimic extracellular matrix (ECM) scale and architecture with reproducible composition and adaptable mechanical properties. However, these materials lack the bioactivity present in natural ECM. ECM-derived scaffolds contain bioactive molecules that exert in vivo mimicking effects as applied for soft tissue engineering, yet do not possess the same flexibility in mechanical property control as some synthetics. The objective of the present study was to combine the controllable properties of a synthetic, biodegradable elastomer with the inherent bioactivity of an ECM derived scaffold. A hybrid electrospun scaffold composed of a biodegradable poly(ester-urethane)urea (PEUU) and a porcine ECM scaffold (urinary bladder matrix, UBM) was fabricated and characterized for its bioactive and physical properties both in vitro and in vivo. Increasing amounts of PEUU led to linear increases in both tensile strength and breaking strain while UBM incorporation led to increased in vitro smooth muscle cell adhesion and proliferation and in vitro mass loss. Subcutaneous implantation of the hybrid scaffolds resulted in increased scaffold degradation and a large cellular infiltrate when compared with electrospun PEUU alone. Electrospun UBM/PEUU combined the attractive bioactivity and mechanical features of its individual components to result in scaffolds with considerable potential for soft tissue engineering applications. PMID:18419942
Stankus, John J; Freytes, Donald O; Badylak, Stephen F; Wagner, William R
Synthetic materials can be electrospun into submicron or nanofibrous scaffolds to mimic extracellular matrix (ECM) scale and architecture with reproducible composition and adaptable mechanical properties. However, these materials lack the bioactivity present in natural ECM. ECM-derived scaffolds contain bioactive molecules that exert in vivo mimicking effects as applied for soft tissue engineering, yet do not possess the same flexibility in mechanical property control as some synthetics. The objective of the present study was to combine the controllable properties of a synthetic, biodegradable elastomer with the inherent bioactivity of an ECM derived scaffold. A hybrid electrospun scaffold composed of a biodegradable poly(ester-urethane)urea (PEUU) and a porcine ECM scaffold (urinary bladder matrix, UBM) was fabricated and characterized for its bioactive and physical properties both in vitro and in vivo. Increasing amounts of PEUU led to linear increases in both tensile strength and breaking strain while UBM incorporation led to increased in vitro smooth muscle cell adhesion and proliferation and in vitro mass loss. Subcutaneous implantation of the hybrid scaffolds resulted in increased scaffold degradation and a large cellular infiltrate when compared with electrospun PEUU alone. Electrospun UBM/PEUU combined the attractive bioactivity and mechanical features of its individual components to result in scaffolds with considerable potential for soft tissue engineering applications. PMID:18419942
Stankus, John J.; Freytes, Donald O.; Badylak, Stephen F.; Wagner, William R.
Novel chitin/nanosilica composite scaffolds for bone tissue engineering applications.
Biopolymers like chitin are widely investigated as scaffolds in bone tissue engineering. Its properties like biocompatibility, biodegradability, non-toxicity, wound healing ability, antibacterial activity, hemostatic property, etc., are widely known. However, these materials are not much bioactive. Addition of material like silica can improve the bioactivity and biocompatibility of chitin. In this work, chitin composite scaffolds containing nanosilica were prepared using chitin hydrogel and their bioactivity, swelling ability and cytotoxicity was analyzed in vitro. These scaffolds were found to be bioactive in simulated body fluid (SBF) and biocompatible when tested with MG 63 cell line. These results suggest that chitin/nanosilica composite scaffolds can be useful for bone tissue engineering applications. PMID:19549539
Madhumathi, K; Sudheesh Kumar, P T; Kavya, K C; Furuike, T; Tamura, H; Nair, S V; Jayakumar, R
Piezoelectric PU/PVDF electrospun scaffolds for wound healing applications.
Previous studies have shown that piezoelectric materials may be used to prepare bioactive electrically charged surfaces. In the current study, polyurethane/polyvinylidene fluoride (PU/PVDF) scaffolds were prepared by electrospinning. The mechanical property and piezoelectric property of the scaffolds were evaluated. The crystalline phase of PVDF in the scaffolds was characterised by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). In vitro cell culture was performed to investigate cytocompatibility of the scaffolds. Wound-healing assay, cell-adhesion assay, quantitative RT-PCR and Western blot analyses were performed to investigate piezoelectric effect of the scaffolds on fibroblast activities. Further, the scaffolds were subcutaneously implanted in Sprague-Dawley (SD) rats to investigate their biocompatibility and the piezoelectric effect on fibrosis in vivo. The results indicated that the electrospinning process had changed PVDF crystalline phase from the nonpiezoelectric ? phase to the piezoelectric ? phase. The fibroblasts cultured on the scaffolds showed normal morphology and proliferation. The fibroblasts cultured on the piezoelectric-excited scaffolds showed enhanced migration, adhesion and secretion. The scaffolds that were subcutaneously implanted in SD rats showed higher fibrosis level due to the piezoelectrical stimulation, which was caused by random animal movements followed by mechanical deformation of the scaffolds. The scaffolds are potential candidates for wound healing applications. PMID:22503631
Guo, Hong-Feng; Li, Zhen-Sheng; Dong, Shi-Wu; Chen, Wei-Jun; Deng, Ling; Wang, Yu-Fei; Ying, Da-Jun
There are two scaffold products designed for meniscal reconstruction or substitution of partial meniscal defects that are currently available in the Europe: the collagen meniscal implant (CMI; Ivy Sports Medicine, Grõfelfing, Germany) and the polymer scaffold (PS; Actifit, Orteq Bioengineering, London, United Kingdom). The CMI has demonstrated improved clinical outcomes compared with baseline in patients with chronic postmeniscectomy symptoms with follow-up ranging from 5 to more than 10 years. There are also several comparative studies that report improved clinical scores in patients with chronic medial meniscus symptoms treated with CMI versus repeat partial meniscectomy, and a lower reoperation rate. Recently, PS insertion was shown to result in improved clinical outcomes in patients with chronic postmeniscectomy symptoms of the medial or lateral meniscus at short-term follow-up. However, there is currently no medium- or long-term data available for the PS. The use of meniscal scaffolds in the acute setting has not been found to result in improved outcomes in most studies. The authors' surgical indications for meniscal scaffold implantation, preferred surgical technique, and postoperative rehabilitation protocol are described. PMID:25172967
Myers, Kevin R; Sgaglione, Nicholas A; Goodwillie, Andrew D
Multi-nozzle deposition for construction of 3D biopolymer tissue scaffolds
scaffolds that is capable of depositing bioactive ingredients. Design/methodology/approach ┬Ł A multi-nozzleMulti-nozzle deposition for construction of 3D biopolymer tissue scaffolds S. Khalil, J. Nam and W deposition through a multi-nozzle heterogeneous system are conducted and presented. Findings ┬Ł Provides
Sun, Wei
Biomaterials 28 (2007) 49014911 Stresscorrosion crack growth of SiNaKMgCaPO bioactive
to be operative for the new bioactive glasses studied here. At higher velocities, hydrodynamic effects reduce their structural integrity, one promising load- bearing application for these glasses may be as coatings to promote
Ritchie, Robert
Design Strategies of Biodegradable Scaffolds for Tissue Regeneration
There are numerous available biodegradable materials that can be used as scaffolds in regenerative medicine. Currently, there is a huge emphasis on the designing phase of the scaffolds. Materials can be designed to have different properties in order to match the specific application. Modifying scaffolds enhances their bioactivity and improves the regeneration capacity. Modifications of the scaffolds can be later characterized using several tissue engineering tools. In addition to the material, cell source is an important component of the regeneration process. Modified materials must be able to support survival and growth of different cell types. Together, cells and modified biomaterials contribute to the remodeling of the engineered tissue, which affects its performance. This review focuses on the recent advancements in the designs of the scaffolds including the physical and chemical modifications. The last part of this review also discusses designing processes that involve viability of cells. PMID:25288907
Bitar, Khalil N; Zakhem, Elie
Investigation of fabrication and environmental effects on bioceramic bone scaffolds
NASA Astrophysics Data System (ADS)
Bioactive ceramic materials like tricalcium phosphates (TCP) have been emerging as viable material alternatives to the current therapies of bone scaffolding to target fracture healing and osteoporosis. Once scaffolds are implanted at the defect site they should provide mechanical and biological functions, ultimately serving to facilitate with surrounding native tissue. Optimal osteogenic signal expression and subsequent differentiation of cells seeded on the scaffold in both in vivo and in vitro conditions is known to be influenced by scaffold properties and biomechanical environmental conditions. Thus, the objective of this research was to investigate the effect of fabrication and environmental variables on the properties of bioceramic scaffolds for bone tissue engineering applications. Specifically, the effect of sintering temperature in the range of 950░C -1150░C of a cost-effective on a large scale manufacturing process, on the physical and mechanical properties of bioceramic bone scaffolds, was investigated. In addition, the effect of a controlled environment was investigated by implementing a bioreactor and bone loading system to study the response of ex vivo trabecular bone to compressive load while perfused with culture medium. Collectively, this thesis demonstrates that: (1) the sintering temperature to fabricate bioceramic scaffolds can be tuned to structural properties, and (2) the use of a controlled mechanical and biochemical environment can enhance bone tissue development. These findings support the development of clinically successful bioceramic scaffolds that may stimulate bone regeneration and scaffold integration while providing structural integrity.
Vivanco Morales, Juan Francisco
Porous Allograft Bone Scaffolds: Doping with Strontium
Strontium (Sr) can promote the process of bone formation. To improve bioactivity, porous allograft bone scaffolds (ABS) were doped with Sr and the mechanical strength and bioactivity of the scaffolds were evaluated. Sr-doped ABS were prepared using the ion exchange method. The density and distribution of Sr in bone scaffolds were investigated by inductively coupled plasma optical emission spectrometry (ICP-OES), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). Controlled release of strontium ions was measured and mechanical strength was evaluated by a compressive strength test. The bioactivity of Sr-doped ABS was investigated by a simulated body fluid (SBF) assay, cytotoxicity testing, and an in vivo implantation experiment. The Sr molar concentration [Sr/(Sr+Ca)] in ABS surpassed 5% and Sr was distributed nearly evenly. XPS analyses suggest that Sr combined with oxygen and carbonate radicals. Released Sr ions were detected in the immersion solution at higher concentration than calcium ions until day 30. The compressive strength of the Sr-doped ABS did not change significantly. The bioactivity of Sr-doped material, as measured by the in vitro SBF immersion method, was superior to that of the Sr-free freeze-dried bone and the Sr-doped material did not show cytotoxicity compared with Sr-free culture medium. The rate of bone mineral deposition for Sr-doped ABS was faster than that of the control at 4 weeks (3.28▒0.23 Ąm/day vs. 2.60▒0.20 Ąm/day; p<0.05). Sr can be evenly doped into porous ABS at relevant concentrations to create highly active bone substitutes. PMID:23922703
Zhao, Yantao; Guo, Dagang; Hou, Shuxun; Zhong, Hongbin; Yan, Jun; Zhang, Chunli; Zhou, Ying
Macroporous nanowire nanoelectronic scaffolds for synthetic tissues
NASA Astrophysics Data System (ADS)
The development of three-dimensional (3D) synthetic biomaterials as structural and bioactive scaffolds is central to fields ranging from cellular biophysics to regenerative medicine. As of yet, these scaffolds cannot electrically probe the physicochemical and biological microenvironments throughout their 3D and macroporous interior, although this capability could have a marked impact in both electronics and biomaterials. Here, we address this challenge using macroporous, flexible and free-standing nanowire nanoelectronic scaffolds (nanoES), and their hybrids with synthetic or natural biomaterials. 3D macroporous nanoES mimic the structure of natural tissue scaffolds, and they were formed by self-organization of coplanar reticular networks with built-in strain and by manipulation of 2D mesh matrices. NanoES exhibited robust electronic properties and have been used alone or combined with other biomaterials as biocompatible extracellular scaffolds for 3D culture of neurons, cardiomyocytes and smooth muscle cells. Furthermore, we show the integrated sensory capability of the nanoES by real-time monitoring of the local electrical activity within 3D nanoES/cardiomyocyte constructs, the response of 3D-nanoES-based neural and cardiac tissue models to drugs, and distinct pH changes inside and outside tubular vascular smooth muscle constructs.
Tian, Bozhi; Liu, Jia; Dvir, Tal; Jin, Lihua; Tsui, Jonathan H.; Qing, Quan; Suo, Zhigang; Langer, Robert; Kohane, Daniel S.; Lieber, Charles M.
Macroporous nanowire nanoelectronic scaffolds for synthetic tissues
The development of three-dimensional (3D) synthetic biomaterials as structural and bioactive scaffolds is central to fields ranging from cellular biophysics to regenerative medicine. As of yet, these scaffolds cannot electrically probe the physicochemical and biological micro-environments throughout their 3D and macroporous interior, although this capability could have a marked impact in both electronics and biomaterials. Here, we address this challenge using macroporous, flexible and free-standing nanowire nanoelectronic scaffolds (nanoES), and their hybrids with synthetic or natural biomaterials. 3D macroporous nanoES mimic the structure of natural tissue scaffolds, and they were formed by self-organization of coplanar reticular networks with built-in strain and by manipulation of 2D mesh matrices. NanoES exhibited robust electronic properties and have been used alone or combined with other biomaterials as biocompatible extracellular scaffolds for 3D culture of neurons, cardiomyocytes and smooth muscle cells. Additionally, we show the integrated sensory capability of the nanoES by real-time monitoring of (i) the local electrical activity within 3D nanoES/cardiomyocyte constructs, (ii) the response of 3D nanoES based neural and cardiac tissue models to drugs, and (iii) distinct pH changes inside and outside tubular vascular smooth muscle constructs. PMID:22922448
Tian, Bozhi; Liu, Jia; Dvir, Tal; Jin, Lihua; Tsui, Jonathan H.; Qing, Quan; Suo, Zhigang; Langer, Robert; Kohane, Daniel S.; Lieber, Charles M.
Soy Protein Scaffold Biomaterials for Tissue Engineering and Regenerative Medicine
NASA Astrophysics Data System (ADS)
Developing functional biomaterials using highly processable materials with tailorable physical and bioactive properties is an ongoing challenge in tissue engineering. Soy protein is an abundant, natural resource with potential use for regenerative medicine applications. Preliminary studies show that soy protein can be physically modified and fabricated into various biocompatible constructs. However, optimized soy protein structures for tissue regeneration (i.e. 3D porous scaffolds) have not yet been designed. Furthermore, little work has established the in vivo biocompatibility of implanted soy protein and the benefit of using soy over other proteins including FDA-approved bovine collagen. In this work, freeze-drying and 3D printing fabrication processes were developed using commercially available soy protein to create porous scaffolds that improve cell growth and infiltration compared to other soy biomaterials previously reported. Characterization of scaffold structure, porosity, and mechanical/degradation properties was performed. In addition, the behavior of human mesenchymal stem cells seeded on various designed soy scaffolds was analyzed. Biological characterization of the cell-seeded scaffolds was performed to assess feasibility for use in liver tissue regeneration. The acute and humoral response of soy scaffolds implanted in an in vivo mouse subcutaneous model was also investigated. All fabricated soy scaffolds were modified using thermal, chemical, and enzymatic crosslinking to change properties and cell growth behavior. 3D printing allowed for control of scaffold pore size and geometry. Scaffold structure, porosity, and degradation rate significantly altered the in vivo response. Freeze-dried soy scaffolds had similar biocompatibility as freeze-dried collagen scaffolds of the same protein content. However, the soy scaffolds degraded at a much faster rate, minimizing immunogenicity. Interestingly, subcutaneously implanted soy scaffolds affected blood glucose and insulin sensitivity levels. Furthermore, soy scaffolds implanted in the intraperitoneal cavity attached to adjacent liver tissue with no abnormalities. In vitro, soy scaffolds supported hMSC viability and transdifferentiation into hepatocyte-like cells. These results support the use of soy scaffolds for liver tissue engineering and for treating metabolic diseases. Based on achievable structural and mechanical properties, as well as systemic effects of ingested and degraded soy proteins, soy protein scaffolds may serve as new multifunctional biomaterials for tissue engineering and regenerative medicine.
Chien, Karen B.
Biodegradable and bioactive nanocomposite (NC) biomaterials with controlled microstructures and able to deliver special drugs have gained increasing attention in bone tissue engineering. In this study, the hydroxyapatite (HAp)/poly(l-lactic acid) (PLLA) NC scaffolds were facilely prepared using solvent evaporation from templating Pickering emulsions stabilized with PLLA-modified HAp (g-HAp) nanoparticles. Then, in vitro mineralization experiments were performed in a simulated body fluid (SBF) to evaluate the bioactivity of the NC scaffolds. Moreover, in vitro drug release of the NC scaffolds using anti-inflammatory drug (ibuprofen, IBU) as the model drug was also investigated. The results showed that the NC scaffolds possessed interconnected pore structures, which could be modulated by varying the g-HAp nanoparticle concentration. The NC scaffolds exhibited excellent bioactivity, since they induced the formation of calcium-sufficient, carbonated apatite nanoparticles on the scaffolds after mineralization in SBF for 3 days. The IBU loaded in the NC scaffolds showed a sustained release profile, and the release kinetic followed the Higuchi model with diffusion process. Thus, solvent evaporation based on Pickering emulsion droplets is a simple and effective method to prepare biodegradable and bioactive porous NC scaffolds for bone repair and replacement applications. PMID:25127362
Hu, Yang; Zou, Shengwen; Chen, Weike; Tong, Zhen; Wang, Chaoyang
Self-Assembling Peptide Nanofiber Scaffolds Accelerate Wound Healing
Cutaneous wound repair regenerates skin integrity, but a chronic failure to heal results in compromised tissue function and increased morbidity. To address this, we have used an integrated approach, using nanobiotechnology to augment the rate of wound reepithelialization by combining self-assembling peptide (SAP) nanofiber scaffold and Epidermal Growth Factor (EGF). This SAP bioscaffold was tested in a bioengineered Human Skin Equivalent (HSE) tissue model that enabled wound reepithelialization to be monitored in a tissue that recapitulates molecular and cellular mechanisms of repair known to occur in human skin. We found that SAP underwent molecular self-assembly to form unique 3D structures that stably covered the surface of the wound, suggesting that this scaffold may serve as a viable wound dressing. We measured the rates of release of EGF from the SAP scaffold and determined that EGF was only released when the scaffold was in direct contact with the HSE. By measuring the length of the epithelial tongue during wound reepithelialization, we found that SAP scaffolds containing EGF accelerated the rate of wound coverage by 5 fold when compared to controls without scaffolds and by 3.5 fold when compared to the scaffold without EGF. In conclusion, our experiments demonstrated that biomaterials composed of a biofunctionalized peptidic scaffold have many properties that are well-suited for the treatment of cutaneous wounds including wound coverage, functionalization with bioactive molecules, localized growth factor release and activation of wound repair. PMID:18183291
Schneider, Aurore; Garlick, Jonathan A.; Egles, Christophe
Structural study of Al2O3-Na2O-CaO-P2O5 bioactive glasses as a function of aluminium content
NASA Astrophysics Data System (ADS)
Calcium phosphate based biomaterials are extensively used in the context of tissue engineering: small changes in composition can lead to significant changes in properties allowing their use in a wide range of applications. Samples of composition (Al2O3)x(Na2O)0.11-x(CaO)0.445(P2O5)0.445, where x = 0, 0.03, 0.05, and 0.08, were prepared by melt quenching. The atomic-scale structure has been studied using neutron diffraction and solid state 27Al MAS NMR, and these data have been rationalised with the determined density of the final glass product. With increasing aluminium concentration the density increases initially, but beyond about 3 mol. % Al2O3 the density starts to decrease. Neutron diffraction data show a concomitant change in the aluminium speciation, which is confirmed by 27Al MAS NMR studies. The NMR data reveal that aluminium is present in 4, 5, and 6-fold coordination and that the relative concentrations of these environments change with increasing aluminium concentration. Materials containing aluminium in 6-fold coordination tend to have higher densities than analogous materials with the aluminium found in 4-fold coordination. Thus, the density changes may readily be explained in terms of an increase in the relative concentration of 4-coordinated aluminium at the expense of 6-fold aluminium as the Al2O3 content is increased beyond 3 mol. %.
Smith, J. M.; King, S. P.; Barney, E. R.; Hanna, J. V.; Newport, R. J.; Pickup, D. M.
Delivery of VEGF using collagen-coated polycaprolactone scaffolds stimulates angiogenesis.
Establishing sufficient vascularization in scaffold remains a challenge for tissue-engineering. To improve angiogenesis, we incorporated vascular endothelial growth factor (VEGF) in collagen-coating over the porous polycaprolactone (PCL) scaffolds. The release kinetics of loaded VEGF from collagen-coated PCL (col-PCL) scaffolds was same as from scaffolds without the collagen. The bioactivity of VEGF delivered by the col-PCL scaffolds was confirmed by human umbilical vein endothelial cell (HUVEC) proliferation and chorioallantoic membrane (CAM) assay. The col-PCL scaffolds were implanted subcutaneously in mice for 7 and 14 days. At day 7, vascularization within scaffolds loaded with VEGF was superior to that in the scaffolds without VEGF. However, the vessel connectivity to host circulatory system was incomplete and restricted to the scaffold edges. At day 14, blood vessels in scaffolds reached density similar to the subcutaneous tissue and were perfusable throughout the implant thickness. Prewashing the scaffolds with saline to remove the unbound growth factor decreased the initial burst release and sustained the VEGF-mediated angiogenesis in vivo. In conclusion, our study demonstrates that physically adsorbed VEGF stimulated angiogenesis in collagen-coated PCL scaffolds. PMID:22213643
Singh, Shivani; Wu, Benjamin M; Dunn, James C Y
A new method of fabricating robust freeform 3D ceramic scaffolds for bone tissue regeneration.
Fabrication of three-dimensional (3D) scaffolds with appropriate mechanical properties and desired architecture for promoting cell growth and new tissue formation is one of the most important efforts in tissue engineering field. Scaffolds fabricated from bioactive ceramic materials such as hydroxyapatite and tricalcium phosphate show promise because of their biological ability to support bone tissue regeneration. However, the use of ceramics as scaffold materials is limited because of their inherent brittleness and difficult processability. The aim of this study was to create robust ceramic scaffolds, which have a desired architecture. Such scaffolds were successfully fabricated by projection-based microstereolithography, and dilatometric analysis was conducted to study the sintering behavior of the ceramic materials. The mechanical properties of the scaffolds were improved by infiltrating them with a polycaprolactone solution. The toughness and compressive strength of these ceramic/polymer scaffolds were about twice those of ceramic scaffolds. Furthermore, the osteogenic gene expression on ceramic/polymer scaffolds was better than that on ceramic scaffolds. Through this study, we overcame the limitations of previous research on fabricating ceramic scaffolds and these new robust ceramic scaffolds may provide a much improved 3D substrate for bone tissue regeneration. PMID:23192318
Seol, Young-Joon; Park, Dong Yong; Park, Ju Young; Kim, Sung Won; Park, Seong Jin; Cho, Dong-Woo
In tissue engineering, the physical and chemical properties of the scaffold mediates cell behavior including regeneration. Thus, a strategy that permits rapid screening of cell-scaffold interactions is critical. Herein, we have prepared eight ōhybridö hydrogel scaffolds in the form of continuous gradients such that a single scaffold contains spatially varied properties. These scaffolds are based on combining an inorganic macromer [methacrylated star polydimethylsiloxane, PDMSstar-MA] and organic macromer [poly(ethylene glycol)diacrylate, PEG-DA] as well both aqueous and organic fabrication solvents. Having previously demonstrated its bioactivity and osteoinductivity, PDMSstar-MA is a particularly powerful component to incorporate into instructive gradient scaffolds based on PEG-DA. The following parameters were varied to produce the different gradients or gradual transitions in: (1) the wt% ratio of PDMSstar-MA to PEG-DA macromers, (2) the total wt% macromer concentration, (3) the number average molecular weight (Mn) of PEG-DA and (4) the Mn of PDMSstar-MA. Upon dividing each scaffold into four ōzonesö perpendicular to the gradient, we were able to demonstrate the spatial variation in morphology, bioactivity, swelling and modulus. Among these gradient scaffolds are those in which swelling and modulus are conveniently decoupled. In addition to rapid screening of cell-material interactions, these scaffolds are well-suited for regeneration of interfacial tissues (e.g. osteochondral tissues) that transition from one tissue type to another. PMID:23707502
Bailey, Brennan M.; Nail, Lindsay N.; Grunlan, Melissa A.
In tissue engineering, the physical and chemical properties of the scaffold mediates cell behavior, including regeneration. Thus a strategy that permits rapid screening of cell-scaffold interactions is critical. Herein, we have prepared eight "hybrid" hydrogel scaffolds in the form of continuous gradients such that a single scaffold contains spatially varied properties. These scaffolds are based on combining an inorganic macromer (methacrylated star polydimethylsiloxane, PDMSstar-MA) and organic macromer (poly(ethylene glycol)diacrylate, PEG-DA) as well as both aqueous and organic fabrication solvents. Having previously demonstrated its bioactivity and osteoinductivity, PDMSstar-MA is a particularly powerful component to incorporate into instructive gradient scaffolds based on PEG-DA. The following parameters were varied to produce the different gradients or gradual transitions in: (1) the wt.% ratio of PDMSstar-MA to PEG-DA macromers, (2) the total wt.% macromer concentration, (3) the number average molecular weight (Mn) of PEG-DA and (4) the Mn of PDMSstar-MA. Upon dividing each scaffold into four "zones" perpendicular to the gradient, we were able to demonstrate the spatial variation in morphology, bioactivity, swelling and modulus. Among these gradient scaffolds are those in which swelling and modulus are conveniently decoupled. In addition to rapid screening of cell-material interactions, these scaffolds are well suited for regeneration of interfacial tissues (e.g. osteochondral tissues) that transition from one tissue type to another. PMID:23707502
Bailey, Brennan M; Nail, Lindsay N; Grunlan, Melissa A
Evaluation of Osteoconductive Scaffolds in the Canine Femoral Multi-Defect Model
Treatment of large segmental bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials. This project was designed to rapidly assess and compare promising biodegradable osteoconductive scaffolds for use in the systematic development of new bone regeneration methodologies that combine scaffolds, sources of osteogenic cells, and bioactive scaffold modifications. Promising biomaterials and scaffold fabrication methods were identified in laboratories at Rutgers, MIT, Integra Life Sciences, and Mayo Clinic. Scaffolds were fabricated from various materials, including poly(L-lactide-co-glycolide) (PLGA), poly(L-lactide-co-?-caprolactone) (PLCL), tyrosine-derived polycarbonate (TyrPC), and poly(propylene fumarate) (PPF). Highly porous three-dimensional (3D) scaffolds were fabricated by 3D printing, laser stereolithography, or solvent casting followed by porogen leaching. The canine femoral multi-defect model was used to systematically compare scaffold performance and enable selection of the most promising substrate(s) on which to add cell sourcing options and bioactive surface modifications. Mineralized cancellous allograft (MCA) was used to provide a comparative reference to the current clinical standard for osteoconductive scaffolds. Percent bone volume within the defect was assessed 4 weeks after implantation using both MicroCT and limited histomorphometry. Bone formed at the periphery of all scaffolds with varying levels of radial ingrowth. MCA produced a rapid and advanced stage of bone formation and remodeling throughout the defect in 4 weeks, greatly exceeding the performance of all polymer scaffolds. Two scaffold constructs, TyrPCPL/TCP and PPF4SLA/HAPLGA Dip, proved to be significantly better than alternative PLGA and PLCL scaffolds, justifying further development. MCA remains the current standard for osteoconductive scaffolds. PMID:23215980
Luangphakdy, Viviane; Walker, Esteban; Shinohara, Kentaro; Pan, Hui; Hefferan, Theresa; Bauer, Thomas W.; Stockdale, Linda; Saini, Sunil; Dadsetan, Mahrokh; Runge, M. Brett; Vasanji, Amit; Griffith, Linda; Yaszemski, Michael
With an increasing demand of biocompatible bone substitutes for the treatment of bone diseases and bone tissue regeneration, bioactive glass composites are being tested to improvise the osteoconductive as well as osteoinductive properties. Nanobioactive glass (nBG) composites, having composition of SiO{sub 2} 70 mol%, CaO 26 mol % and P{sub 2}O{sub 5} 4 mol% were prepared by Freeze drying method using PEG-PPG-PEG co-polymer. Polymer addition improves the mechanical strength and porosity of the scaffold of nBG. Nano Bioactive glass composites upon implantation undergo specific reactions leading to the formation of crystalline hydroxyapatite (HA). This is tested in vitro using Simulated Body Fluid (SBF). This high strength hydroxyapatite (HA) layer acts as osteoconductive in cellular environment, by acting as mineral base of bones, onto which new bone cells proliferate leading to new bone formation. Strength of the nBG composites as well as HA is in the range of cortical and cancellous bone, thus proving significant for bone tissue regeneration substitutes.
Shrivastava, Pragya; Dalai, Sridhar; Vijayalakshmi, S. [Centre for Research in Nanotechnology and Science, IIT Bombay (India); Sudera, Prerna; Sivam, Santosh Param [Amity Institute of Nanotechnology, Amity University, Noida, Uttar Pradesh-201303 (India); Sharma, Pratibha [Dept of Energy Science and Engineering, IIT Bombay (India)
The regeneration of functional tissue in osseous defects is a formidable challenge in orthopedic surgery. In the present study, a novel biomimetic composite scaffold, here called nano-hydroxyapatite (HA)/poly-?-caprolactone (PCL) was fabricated using a selective laser sintering technique. The macrostructure, morphology, and mechanical strength of the scaffolds were characterized. Scanning electronic microscopy (SEM) showed that the nano-HA/PCL scaffolds exhibited predesigned, well-ordered macropores and interconnected micropores. The scaffolds have a range of porosity from 78.54% to 70.31%, and a corresponding compressive strength of 1.38 MPa to 3.17 MPa. Human bone marrow stromal cells were seeded onto the nano-HA/PCL or PCL scaffolds and cultured for 28 days in vitro. As indicated by the level of cell attachment and proliferation, the nano-HA/PCL showed excellent biocompatibility, comparable to that of PCL scaffolds. The hydrophilicity, mineralization, alkaline phosphatase activity, and Alizarin Red S staining indicated that the nano-HA/PCL scaffolds are more bioactive than the PCL scaffolds in vitro. Measurements of recombinant human bone morphogenetic protein-2 (rhBMP-2) release kinetics showed that after nano-HA was added, the material increased the rate of rhBMP-2 release. To investigate the in vivo biocompatibility and osteogenesis of the composite scaffolds, both nano-HA/PCL scaffolds and PCL scaffolds were implanted in rabbit femur defects for 3, 6, and 9 weeks. The wounds were studied radiographically and histologically. The in vivo results showed that both nano-HA/PCL composite scaffolds and PCL scaffolds exhibited good biocompatibility. However, the nano-HA/PCL scaffolds enhanced the efficiency of new bone formation more than PCL scaffolds and fulfilled all the basic requirements of bone tissue engineering scaffolds. Thus, they show large potential for use in orthopedic and reconstructive surgery. PMID:24204147
Xia, Yan; Zhou, Panyu; Cheng, Xiaosong; Xie, Yang; Liang, Chong; Li, Chao; Xu, Shuogui
Injectable scaffolds for bone regeneration.
Clinical treatments of significant bone defects involve invasive procedures such as the application of auto- and allografts. These procedures present many limitations including the potential for infection and rejection. There is therefore a need to develop novel therapeutic strategies able to exploit the natural regenerative potential of bone and that can be delivered in a less invasive manner. Among the materials studied for the development of novel scaffolds, stimuli-responsive gels containing hydroxyapatite and carbon nanotubes as nanofillers have generated great interest. In the present work, chitosan gels containing chitosan grafted CNTs and chitosan-hydroxyapatite complex have been formed by cross-linking with glycerol phosphate. The addition of the nanofillers afforded hydrogels with a faster sol/gel transition at 37 ░C and enhanced mechanical properties. The thermosensitive composite gels also showed a good bioactivity profile associated with potential for the prolonged delivery of protein drugs. The inclusion of chemically cross-linked CNTs and HA in thermosensitive gels afforded injectable composite materials with enhanced properties, including reduction of gelation time, improved mechanical properties, good bioactivity, and prolonged drug release. PMID:25296391
Yasmeen, Sabina; Lo, Man Kit; Bajracharya, Salina; Roldo, Marta
Study on a hydroxypropyl chitosan-gelatin based scaffold for corneal stroma tissue engineering
NASA Astrophysics Data System (ADS)
Hydroxypropyl chitosan (HPCTS) was crosslinked with gelatin (GEL) and chondroitin sulfate (CS) by 1,4-butanediol diglycidyl ether to synthesize a scaffold. In this study, this scaffold was tested in physical and biological characteristics as a bioactive corneal stroma surrogate. The results showed the scaffold exhibited 83-88% light transmission values at wavelengths of visible light. Besides that, the scaffold had 96% water content and allowed NaCl and glucose to permeate. Moreover, it was suitable for keratocytes growing on its surface. In the biological part, we compared the scaffold with CS-free ones to investigate the potential effect of CS and found out that CS notablely improved cell compatibility of the scaffold.
Wang, Shilu; Liu, Wanshun; Han, Baoqin; Yang, Lingling
Electrospun cartilage-derived matrix scaffolds for cartilage tissue engineering.
Macroscale scaffolds created from cartilage-derived matrix (CDM) demonstrate chondroinductive or chondro-inductive properties, but many fabrication methods do not allow for control of nanoscale architecture. In this regard, electrospun scaffolds have shown significant promise for cartilage tissue engineering. However, nanofibrous materials generally exhibit a relatively small pore size and require techniques such as multilayering or the inclusion of sacrificial fibers to enhance cellular infiltration. The objectives of this study were (1) to compare multilayer to single-layer electrospun poly(?-caprolactone) (PCL) scaffolds for cartilage tissue engineering, and (2) to determine whether incorporation of CDM into the PCL fibers would enhance chondrogenesis by human adipose-derived stem cells (hASCs). PCL and PCL-CDM scaffolds were prepared by sequential collection of 60 electrospun layers from the surface of a grounded saline bath into a single scaffold, or by continuous electrospinning onto the surface of a grounded saline bath and harvest as a single-layer scaffold. Scaffolds were seeded with hASCs and evaluated over 28 days in culture. The predominant effects on hASCs of incorporation of CDM into scaffolds were to stimulate sulfated glycosaminoglycan synthesis and COL10A1 gene expression. Compared with single-layer scaffolds, multilayer scaffolds enhanced cell infiltration and ACAN gene expression. However, compared with single-layer constructs, multilayer PCL constructs had a much lower elastic modulus, and PCL-CDM constructs had an elastic modulus approximately 1% that of PCL constructs. These data suggest that multilayer electrospun constructs enhance homogeneous cell seeding, and that the inclusion of CDM stimulates chondrogenesis-related bioactivity. ® 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3998-4008, 2014. PMID:24375991
Garrigues, N William; Little, Dianne; Sanchez-Adams, Johannah; Ruch, David S; Guilak, Farshid
Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds.
Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of a model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of the drug over the period of 28days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in the culture medium. The formation of a mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration. PMID:24794894
Gaharwar, Akhilesh K; Mihaila, Silvia M; Kulkarni, Ashish A; Patel, Alpesh; Di Luca, Andrea; Reis, Rui L; Gomes, Manuela E; van Blitterswijk, Clemens; Moroni, Lorenzo; Khademhosseini, Ali
Multi-nozzle deposition for construction of 3D biopolymer tissue scaffolds
Purpose ¢ To introduce recent research and development of biopolymer deposition for freeform fabrication of three-dimensional tissue scaffolds that is capable of depositing bioactive ingredients. Design\\/methodology\\/approach ¢ A multi-nozzle biopolymer deposition system is developed, which is capable of extruding biopolymer solutions and living cells for freeform construction of 3D tissue scaffolds. The deposition process is biocompatible and occurs at room
S. Khalil; J. Nam; W. Sun
Nanohydroxyapatite (n-HA)/nylon 6,6 composite scaffolds were produced by means of the salt-leaching/solvent casting technique. NaCl with a distinct range size was used with the aim of optimizing the pore network. Composite powders with different n-HA contents (40%, 60%) for scaffold fabrication were synthesized and tested. The composite scaffolds thus obtained were characterized for their microstructure, mechanical stability and strength, and bioactivity. The microstructure of the composite scaffolds possessed a well-developed interconnected porosity with approximate optimal pore size ranging from 200 to 500 ?m, ideal for bone regeneration and vascularization. The mechanical properties of the composite scaffolds were evaluated by compressive strength and modulus tests, and the results confirmed their similarity to cortical bone. To characterize bioactivity, the composite scaffolds were immersed in simulated body fluid for different lengths of time and results monitored by scanning electron microscopy and energy dispersive X-ray microanalysis to determine formation of an apatite layer on the scaffold surface. PMID:21904455
Mehrabanian, Mehran; Nasr-Esfahani, Mojtaba
The extracellular matrix (ECM) is a complex organization of structural proteins found within tissues and organs. Heterogeneous tissues with spatially and temporally modulated properties play an important role in organism physiology. Here we present a benzophenone (BP) based direct, photolithographic approach to spatially pattern solution phase biomolecules within collagen-GAG (CG) scaffolds and demonstrate creation of a wide range of patterns composed of multiple biomolecular species in a manner independent from scaffold fabrication steps. We demonstrate the ability to immobilize biomolecules at surface densities of up to 1000 ligands per square micron on the scaffold strut surface and to depths limited by the penetration depth of the excitation source into the scaffold structure. Importantly, while BP photopatterning does further crosslink the CG scaffold, evidenced by increased mechanical properties and collagen crystallinity, it does not affect scaffold microstructural or compositional properties or negatively influence cell adhesion, viability, or proliferation. We show that covalently photoimmobilized fibronectin within a CG scaffold significantly increases the speed of MC3T3-E1 cell attachment relative to the bare CG scaffold or non-specifically adsorbed fibronectin, suggesting that this approach can be used to improve scaffold bioactivity. Our findings, on the whole, establish the use of direct, BP photolithography as a methodology for covalently incorporating activity-improving biochemical cues within 3D collagen biomaterial scaffolds with spatial control over biomolecular deposition. PMID:21397322
Martin, Teresa A.; Caliari, Steven R.; Williford, Paul D.; Harley, Brendan A.; Bailey, Ryan C.
Three-dimensional printing (3DP) is a rapid prototyping technique that can create complex 3D structures by inkjet printing of a liquid binder onto powder biomaterials for tissue engineering scaffolds. Direct fabrication of scaffolds from 3DP, however, imposes a limitation on material choices by manufacturing processes. In this study, we report an indirect 3DP approach wherein a positive replica of desired shapes was printed using gelatin particles, and the final scaffold was directly produced from the printed mold. To create patient-specific scaffolds that match precisely to a patient's external contours, we integrated our indirect 3DP technique with imaging technologies and successfully created custom scaffolds mimicking human mandibular condyle using polycaprolactone and chitosan for potential osteochondral tissue engineering. To test the ability of the technique to precisely control the internal morphology of the scaffolds, we created orthogonal interconnected channels within the scaffolds using computer-aided-design models. Because very few biomaterials are truly osteoinductive, we modified inert 3D printed materials with bioactive apatite coating. The feasibility of these scaffolds to support cell growth was investigated using bone marrow stromal cells (BMSC). The BMSCs showed good viability in the scaffolds, and the apatite coating further enhanced cellular spreading and proliferation. This technique may be valuable for complex scaffold fabrication. PMID:24060622
Lee, Ju-Yeon; Choi, Bogyu; Wu, Benjamin; Lee, Min
An electrically conductive polypyrrole (PPy) doped with a bioactive agent is an emerging functional biomaterial for tissue engineering. We therefore used chondroitin sulfate (CS)-doped PPy coating to modify initially electrically insulating polylactide resulting in novel osteogenic scaffolds. In situ chemical oxidative polymerization was used to obtain electrically conductive PPy coating on poly-96L/4D-lactide (PLA) nonwoven scaffolds. The coated scaffolds were characterized and their electrical conductivity was evaluated in hydrolysis. The ability of the coated and conductive scaffolds to enhance proliferation and osteogenic differentiation of human adipose stem cells (hASCs) under electrical stimulation (ES) in three-dimensional (3D) geometry was compared to the noncoated PLA scaffolds. Electrical conductivity of PPy-coated PLA scaffolds (PLA-PPy) was evident at the beginning of hydrolysis, but decreased during the first week of incubation due to de-doping. PLA-PPy scaffolds enhanced hASC proliferation significantly compared to the plain PLA scaffolds at 7 and 14 days. Furthermore, the alkaline phosphatase (ALP) activity of the hASCs was generally higher in PLA-PPy seeded scaffolds, but due to patient variation, no statistical significance could be determined. ES did not have a significant effect on hASCs. This study highlights the potential of novel PPy-coated PLA scaffolds in bone tissue engineering. PMID:23126228
Pelto, Jani; Bjorninen, Miina; Palli, Aliisa; Talvitie, Elina; Hyttinen, Jari; Mannerstrom, Bettina; Suuronen Seppanen, Riitta; Kellomaki, Minna; Miettinen, Susanna; Haimi, Suvi
A novel porcine acellular dermal matrix scaffold used in periodontal regeneration
Regeneration of periodontal tissue is the most promising method for restoring periodontal structures. To find a suitable bioactive three-dimensional scaffold promoting cell proliferation and differentiation is critical in periodontal tissue engineering. The objective of this study was to evaluate the biocompatibility of a novel porcine acellular dermal matrix as periodontal tissue scaffolds both in vitro and in vivo. The scaffolds in this study were purified porcine acellular dermal matrix (PADM) and hydroxyapatite-treated PADM (HA-PADM). The biodegradation patterns of the scaffolds were evaluated in vitro. The biocompatibility of the scaffolds in vivo was assessed by implanting them into the sacrospinal muscle of 20 New Zealand white rabbits. The hPDL cells were cultured with PADM or HA-PADM scaffolds for 3, 7, 14, 21 and 28 days. Cell viability assay, scanning electron microscopy (SEM), hematoxylin and eosin (H&E) staining, immunohistochemistry and confocal microscopy were used to evaluate the biocompatibility of the scaffolds. In vitro, both PADM and HA-PADM scaffolds displayed appropriate biodegradation pattern, and also, demonstrated favorable tissue compatibility without tissue necrosis, fibrosis and other abnormal response. The absorbance readings of the WST-1 assay were increased with the time course, suggesting the cell proliferation in the scaffolds. The hPDL cells attaching, spreading and morphology on the surface of the scaffold were visualized by SEM, H&E staining, immnuohistochemistry and confocal microscopy, demonstrated that hPDL cells were able to grow into the HA-PADM scaffolds and the amount of cells were growing up in the course of time. This study proved that HA-PADM scaffold had good biocompatibility in animals in vivo and appropriate biodegrading characteristics in vitro. The hPDL cells were able to proliferate and migrate into the scaffold. These observations may suggest that HA-PADM scaffold is a potential cell carrier for periodontal tissue regeneration. PMID:23492902
Guo, Jing; Chen, Hui; Wang, Ying; Cao, Cheng-Bo; Guan, Guo-Qiang
Inorganic-organic hydrogel scaffolds for tissue engineering
NASA Astrophysics Data System (ADS)
Analogous to the extracellular matrix (ECM) of natural tissues, properties of a tissue engineering scaffold direct cell behavior and thus regenerated tissue properties. These include both physical properties (e.g. morphology and modulus) and chemical properties (e.g. hydrophobicity, hydration and bioactivity). Notably, recent studies suggest that scaffold properties (e.g. modulus) may be as potent as growth factors in terms of directing stem cell fate. Thus, 3D scaffolds possessing specific properties modified for optimal cell regeneration have the potential to regenerate native-like tissues. Photopolymerizable poly(ethylene glycol) diacrylate (PEG-DA)-based hydrogels are frequently used as scaffolds for tissue engineering. They are ideal for controlled studies of cell-material interactions due to their poor protein adsorption in the absence of adhesive ligands thereby making them "biological blank slates". However, their range of physical and chemical properties is limited. Thus, hydrogel scaffolds which maintain the benefits of PEG-DA but possess a broader set of tunable properties would allow the establishment of predictive relationships between scaffold properties, cell behavior and regenerated tissue properties. Towards this goal, this work describes a series of unique hybrid inorganic-organic hydrogel scaffolds prepared using different solvents and also in the form of continuous gradients. Properties relevant to tissue regeneration were investigated including: swelling, morphology, modulus, degradation rates, bioactivity, cytocompatibility, and protein adhesion. These scaffolds were based on the incorporation of hydrophobic, bioactive and osteoinductive methacrylated star polydimethylsiloxane (PDMSstar-MA) ["inorganic component"] into hydrophilic PEG-DA ["organic component"]. The following parameters were varied: molecular weight (Mn) of PEG-DA (Mn = 3k & 6k g/mol) and PDMSstar-MA (Mn = 1.8k, 7k, 14k), ratio of PDMSstar-MA to PEG-DA (0:100 to 20:80), total macromer concentration (5 to 20 wt%) and utilizing either water or dichloromethane (DCM) fabrication solvent. The use of DCM produced solvent induced phase separation (SIPS) resulting in scaffolds with macroporous morphologies, enhanced modulus and a more homogenous distribution of the PDMSstar-MA component throughout. These hybrid hydrogel scaffolds were prepared in the form of continuous gradients such that a single scaffold contains spatially varied chemical and physical properties. Thus, cell-material interaction studies may be conducted more rapidly at different "zones" defined along the gradient. These gradients are also expected to benefit the regeneration of the osteochondral interface, an interfacial tissue that gradually transitions in tissue type. The final aspect of this work was focused on enhancing the osteogenic potential of PDMS via functionalization with amine and phosphonate. Both amine and phosphonate moieties have demonstrated bioactivity. Thus, it was expected that these properties will be enhanced for amine and phosphonate functionalized PDMS. The subsequent incorporation of these PDMS-based macromers into the previously described PEG-DA scaffold system is expected to be valuable for osteochondral tissue regeneration.
Bailey, Brennan Margaret
Food bioactives are physiologically active components in food or dietary supplements of plant or animal origin that have a\\u000a role in health beyond basic nutrition. The addition of bioactive components to foods, particularly those foods that are consumed\\u000a as part of the normal diet of target populations, offers opportunities for improving the health and well-being of consumers.\\u000a The interest of
M. A. Augustin; L. Sanguansri
In this study, calcium phosphate cement (CPC)-based scaffold with unidirectional lamellar pore structure was fabricated by unidirectional freeze casting. Poly(lactic-co-glycolic acid) (PLGA) was infiltrated into the CPC scaffold to improve its strength and toughness, which compromised the bioactivity and osteoconductivity of CPC. Collagen (Col) was immobilized on the pore surface of the PLGA/CPC scaffold to enhance the bioactivity of the scaffold using plasma treatment under the ammonia (NH(3)) atmosphere. The immobilization of collagen was characterized by infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Compared to the PLGA/CPC composite scaffold, the Col/PLGA/CPC composite scaffold had higher contact angle, porosity and water absorption, while the compressive strength of both scaffolds was comparable. Rat bone marrow mesenchymal stem cells (rMSCs) seeded on the Col/PLGA/CPC scaffold showed markedly improved cell seeding, attachment, proliferation and differentiation than those on the PLGA/CPC scaffold. These results suggest that the surface immobilization of collagen by plasma treatment can improve the bioactivity of the PLGA/CPC scaffold and the Col/PLGA/CPC composite scaffold is a promising candidate for bone tissue engineering. PMID:23201739
He, Fupo; Li, Jiyan; Ye, Jiandong
In the field of tissue engineering and regenerative medicine there is significant unmet need for critically-sized, fully degradable biomaterial scaffold systems with tunable properties for optimizing tissue formation in vitro and tissue regeneration in vivo. To address this need, we have developed a silk-based scaffold platform that has tunable material properties, including localized and bioactive functionalization, degradation rate, and mechanical properties and that provides arrays of linear hollow channels for delivery of oxygen and nutrients throughout the scaffold bulk. The scaffolds can be assembled with dimensions that range from millimeters to centimeters, addressing the need for a critically-sized platform for tissue formation. We demonstrate that the hollow channel arrays support localized and confluent endothelialization. This new platform offers a unique and versatile tool for engineering `tailored' scaffolds for a range of tissue engineering and regenerative medicine needs. PMID:23036961
Wray, Lindsay S.; Rnjak-Kovacina, Jelena; Mandal, Biman B.; Schmidt, Daniel F.; Seok, Eun; Kaplan, David L.
There is increasing interest in developing scaffolds with therapeutic and antibacterial potential for bone tissue engineering. Silver is a proven antibacterial agent which bacteria such as MRSA have little or no defense against. Using an ion exchange method, silver ions have been introduced into 45S5 Bioglass(«) based scaffolds that were fabricated using the foam replication technique. This technique allows the introduction of Ag(+) ions onto the surface of the scaffold without compromising the scaffold bioactivity and other physical properties such as porosity. Controlling the amount of Ag(+) ions introduced onto the surface of the scaffold was achieved by tailoring the ion exchange parameters to fabricate samples with repeatable and predictable Ag(+) ion release behavior. In vitro studies in simulated body fluid were carried out to ensure that the scaffolds maintained their bioactivity after the introduction of Ag(+) ions. It was also shown that the addition of low concentrations (2000:1 w/w) of silver ions supported the attachment and viability of human periodontal ligament stromal cells on the 3D scaffolds. This work has thus confirmed ion exchange as an effective technique to introduce Ag(+) ions into 45S5 Bioglass(«) scaffolds without compromising the basic properties of 45S5 Bioglass(«) which are required for applications in bone tissue engineering. PMID:21293911
Newby, P J; El-Gendy, R; Kirkham, J; Yang, X B; Thompson, I D; Boccaccini, A R
Bioactive oligosaccharide natural products.
Covering up to December 2013. Oligosaccharide natural products target a wide spectrum of biological processes including disruption of cell wall biosynthesis, interference of bacterial translation, and inhibition of human ?-amylase. Correspondingly, oligosaccharides possess the potential for development as treatments of such diverse diseases as bacterial infections and type II diabetes. Despite their potent and selective activities and potential clinical relevance, isolated bioactive secondary metabolic oligosaccharides are less prevalent than other classes of natural products and their biosynthesis has received comparatively less attention. This review highlights the unique modes of action and biosynthesis of four classes of bioactive oligosaccharides: the orthosomycins, moenomycins, saccharomicins, and acarviostatins. PMID:24883430
McCranie, Emilianne K; Bachmann, Brian O
Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration. PMID:25033438
Shen, Yue; Yang, Shizhou; Liu, Jianli; Xu, Huazi; Shi, Zhongli; Lin, Zhongqing; Ying, Xiaozhou; Guo, Peng; Lin, Tiao; Yan, Shigui; Huang, Qing; Peng, Lei
Scaffolds in Tendon Tissue Engineering
Tissue engineering techniques using novel scaffold materials offer potential alternatives for managing tendon disorders. Tissue engineering strategies to improve tendon repair healing include the use of scaffolds, growth factors, cell seeding, or a combination of these approaches. Scaffolds have been the most common strategy investigated to date. Available scaffolds for tendon repair include both biological scaffolds, obtained from mammalian tissues, and synthetic scaffolds, manufactured from chemical compounds. Preliminary studies support the idea that scaffolds can provide an alternative for tendon augmentation with an enormous therapeutic potential. However, available data are lacking to allow definitive conclusion on the use of scaffolds for tendon augmentation. We review the current basic science and clinical understanding in the field of scaffolds and tissue engineering for tendon repair. PMID:22190961
Longo, Umile Giuseppe; Lamberti, Alfredo; Petrillo, Stefano; Maffulli, Nicola; Denaro, Vincenzo
NASA Astrophysics Data System (ADS)
When bone is damaged, a scaffold can temporarily replace it in the site of injury and incite bone tissue to repair itself. A biodegradable scaffold resorbs into the body, generating non-toxic degradation products as new tissue reforms; a bioactive scaffold encourages the surrounding tissue to regenerate. In the present study, we make composite biodegradable and bioactive scaffolds using poly-DL-lactide (PDLLA), a biodegradable polymer, and incorporate Bioglass 45S5 (BG) to stimulate scaffold bioactivity. BG has an interesting trait when immersed in body fluid, a layer of hydroxycarbonate apatite, similar to the inorganic component of bone, forms on its surface. It is of utmost importance to understand the fate of BG throughout the scaffoldÆs processing in order to assess the scaffoldÆs bioactivity. In this study, the established different stages of BG reactivity have been verified by monitoring pH during BG dissolution experiments and by conducting an elemental analysis using inductively coupled plasma optical emission spectroscopy (ICP-OES). The composite scaffolds are synthesized by the solvent casting and particulate leaching technique and their morphology assessed by scanning electron microscopy (SEM). To understand the transformations occurred in BG during scaffold synthesis, BG as received, as well BG treated in acetone and water (the fluids involved in scaffold processing) are characterized by Fourier transform infrared (FTIR), and x-ray photoelectron spectroscopy (XPS). The results are then compared with BG extracted from scaffolds after processing. BG has been determined to start reacting during the scaffold processing. In addition, its reactivity is influenced by BG particle size. The study suggests that the presence of the polymer provides a reactive environment for BG due to pH effects. Teflon molds in scaffold fabrication are inert and biocompatibile, but their stiffness presents a challenge during de-molding. Silicone-based and polyurethane molds are attractive because they are flexible. However, there is a possibility that silicone leaches either from the material itself or the agents used to enhance their performance onto the scaffold. The second study in this thesis focuses on different types of such flexible substrates (Sil940, polyurethane, polyether, polydimethylsiloxane). The presence of Si in PDLLA films prepared on each material is inspected using XPS. Films made on all four materials are found to contain Si, indicative of the dissolution of part of the substrate in the film. However, silicon in the Si-containing catalysts used in the synthesis of polyethers is not transferred to samples, when the polyether substrate is plasma coated.
Abdollahi, Sara
Polymer-coated 45S5 Bioglass(«) (BG)/chitosan-polycaprolactone (BG/CS-PCL) bilayered composite scaffolds were prepared via foam replication and freeze-drying techniques for application in osteochondral tissue engineering. The CS-PCL coated and uncoated BG scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The mechanical properties of the coated scaffolds were significantly improved in comparison to uncoated scaffolds. The bioactivity and biodegradation behavior of scaffolds were studied in simulated body fluid (SBF) for up to 28 days. The interface between the BG scaffold and the polymer coating layer was observed by SEM and a suitable interpenetration of the polymer into the scaffold struts was found. The effects of coated and uncoated BG scaffolds on MG-63 osteoblast-like cells were evaluated by cell viability, adhesion and proliferation. ® 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4510-4518, 2014. PMID:24677705
Yao, Qingqing; Nooeaid, Patcharakamon; Detsch, Rainer; Roether, Judith A; Dong, Yanming; Goudouri, Ourania-Menti; Schubert, Dirk W; Boccaccini, Aldo R
New macroporous calcium phosphate glass ceramic for guided bone regeneration
This work describes a method to obtain macroporous resorbable glass and glass ceramic scaffolds with controlled biodegradability for tissue engineering applications. The constructs consisted of glass and glass ceramics in the system P2O5¢CaO¢Na2O¢TiO2 and they were prepared by foaming a slurry of glass particles by addition of a H2O2 solution, and subsequent sintering of the porous structures obtained. Different thermal
Melba Navarro; Sergio del Valle; Salvador Mart??nez; Stefania Zeppetelli; Luigi Ambrosio; Josep Anton Planell; Maria Pau Ginebra
Three-dimensional polymeric scaffolds provide structural support and function as substrates for cells and bioactive molecules necessary for tissue regeneration. Noninvasive real-time imaging of scaffolds and/or the process of tissue formation within the scaffold remains a challenge. Microcomputed tomography, the widely used technique to characterize polymeric scaffolds, shows poor contrast for scaffolds immersed in biological fluids, thereby limiting its utilities under physiological conditions. In this article, multiscale photoacoustic microscopy (PAM), consisting of both acoustic-resolution PAM (AR-PAM) and optical-resolution PAM (OR-PAM), was employed to image and characterize single-walled carbon-nanotube (SWNT)¢incorporated poly(lactic-co-glycolic acid) polymer scaffolds immersed in biological buffer. SWNTs were incorporated to reinforce the mechanical properties of the scaffolds, and to enhance the photoacoustic signal from the scaffolds. By choosing excitation wavelengths of 570 and 638?nm, multiscale PAM could spectroscopically differentiate the photoacoustic signals generated from blood and from carbon-nanotube-incorporated scaffolds. OR-PAM, providing a fine lateral resolution of 2.6??m with an adequate tissue penetration of 660??m, successfully quantified the average porosity and pore size of the scaffolds to be 86.5%▒1.2% and 153▒15??m in diameter, respectively. AR-PAM further extended the tissue penetration to 2?mm at the expense of lateral resolution (45??m). Our results suggest that PAM is a promising tool for noninvasive real-time imaging and monitoring of tissue engineering scaffolds in vitro, and in vivo under physiological conditions. PMID:22082018
Cai, Xin; Paratala, Bhavna S.; Hu, Song
Development of Bioactive Peptide Amphiphiles for Therapeutic Cell Delivery
There is great clinical interest in cell-based therapies for ischemic tissue repair in cardiovascular disease. However, the regenerative potential of these therapies is limited due to poor cell viability and minimal retention following application. We report here the development of bioactive peptide amphiphile nanofibers displaying the fibronectin-derived RGDS cell adhesion epitope as a scaffold for therapeutic delivery of bone marrow derived stem and progenitor cells. When grown on flat substrates, a binary peptide amphiphile system consisting of 10% by weight RGDS-containing molecules and 90% negatively charged diluent molecules was found to promote optimal cell adhesion. This binary system enhanced adhesion 1.4 fold relative to substrates composed of only the non-bioactive diluent. Additionally, no enhancement was found upon scrambling the epitope and adhesion was no longer enhanced upon adding soluble RGDS to the cell media, indicating RGDS-specific adhesion. When encapsulated within self-assembled scaffolds of the binary RGDS nanofibers in vitro, cells were found to be viable and proliferative, increasing in number by 5.5 times after only 5 days, an effect again lost upon adding soluble RGDS. Cells encapsulated within a non-bioactive scaffold and those within a binary scaffold with scrambled epitope showed minimal viability and no proliferation. Cells encapsulated within this RGDS nanofiber gel also increase in endothelial character, evident by a decrease in the expression of CD34 paired with an increase in the expression of endothelial-specific markers VE-Cadherin, VEGFR2, and eNOS after 5 days. In an in vivo study, nanofibers and luciferase-expressing cells were co-injected subcutaneously in a mouse model. The binary RGDS material supported these cells in vivo, evident by a 3.2 fold increase in bioluminescent signal attributable to viable cells; this suggests the material has an anti-apoptotic and/or proliferative effect on the transplanted bone marrow cells. We conclude that the binary RGDS-presenting nanofibers developed here demonstrate enhanced viability, proliferation, and adhesion of associated bone marrow derived stem and progenitor cells. This study suggests potential for this material as a scaffold to overcome current limitations of stem cell therapies for ischemic diseases. PMID:19635599
Webber, Matthew J.; Tongers, Jorn; Renault, Marie-Ange; Roncalli, Jerome G.; Losordo, Douglas W.
Effect of different sintering methods on bioactivity and release of proteins from PLGA microspheres.
Macromolecule release from poly(d,l-lactide-co-glycolide) (PLGA) microspheres has been well-characterized, and is a popular approach for delivering bioactive signals from tissue-engineered scaffolds. However, the effect of some processing solvents, sterilization, and mineral incorporation (when used in concert) on long-term release and bioactivity has seldom been addressed. Understanding these effects is of significant importance for microsphere-based scaffolds, given that these scaffolds are becoming increasingly more popular, yet growth factor activity following sintering and/or sterilization is heretofore unknown. The current study evaluated the 6-week release of transforming growth factor (TGF)-?3 and bone morphogenetic protein (BMP)-2 from PLGA and PLGA/hydroxyapatite (HAp) microspheres following exposure to ethanol (EtOH), dense phase carbon dioxide (CO2), or ethylene oxide (EtO). EtO was chosen based on its common use in scaffold sterilization, whereas EtOH and CO2 were chosen given their importance in sintering microspheres together to create scaffolds. Release supernatants were then used in an accelerated cell stimulation study with human bone marrow stromal cells (hBMSCs) with monitoring of gene expression for major chondrogenic and osteogenic markers. Results indicated that in microspheres without HAp, EtOH exposure led to the greatest amount of delivery, while those treated with CO2 delivered the least growth factor. In contrast, formulations with HAp released almost half as much protein, regardless of EtOH or CO2 exposure. Notably, EtO exposure was not found to significantly affect the amount of protein released. Cell stimulation studies demonstrated that eluted protein samples performed similarly to positive controls in PLGA-only formulations, and ambiguously in PLGA/HAp composites. In conclusion, the use of EtOH, subcritical CO2, and EtO in microsphere-based scaffolds may have only slight adverse effects, and possibly even desirable effects in some cases, on protein availability and bioactivity. PMID:23910352
Dormer, Nathan H; Gupta, Vineet; Scurto, Aaron M; Berkland, Cory J; Detamore, Michael S
Effect of different sintering methods on bioactivity and release of proteins from PLGA microspheres
Macromolecule release from poly(d,l-lactide-co-glycolide) (PLGA) microspheres has been well-characterized, and is a popular approach for delivering bioactive signals from tissue-engineered scaffolds. However, the effect of some processing solvents, sterilization, and mineral incorporation (when used in concert) on long-term release and bioactivity has seldom been addressed. Understanding these effects is of significant importance for microsphere-based scaffolds, given that these scaffolds are becoming increasingly more popular, yet growth factor activity following sintering and/or sterilization is heretofore unknown. The current study evaluated the 6-week release of transforming growth factor (TGF)-?3 and bone morphogenetic protein (BMP)-2 from PLGA and PLGA/hydroxyapatite (HAp) microspheres following exposure to ethanol (EtOH), dense phase carbon dioxide (CO2), or ethylene oxide (EtO). EtO was chosen based on its common use in scaffold sterilization, whereas EtOH and CO2 were chosen given their importance in sintering microspheres together to create scaffolds. Release supernatants were then used in an accelerated cell stimulation study with human bone marrow stromal cells (hBMSCs) with monitoring of gene expression for major chondrogenic and osteogenic markers. Results indicated that in microspheres without HAp, EtOH exposure led to the greatest amount of delivery, whilst those treated with CO2 delivered the least growth factor. In contrast, formulations with HAp released almost half as much protein, regardless of EtOH or CO2 exposure. Notably, EtO exposure was not found to significantly affect the amount of protein released. Cell stimulation studies demonstrated that eluted protein samples performed similarly to positive controls in PLGA-only formulations, and ambiguously in PLGA/HAp composites. In conclusion, the use of EtOH, subcritical CO2, and EtO in microsphere-based scaffolds may have only slight adverse effects, and possibly even desirable effects in some cases, on protein availability and bioactivity. PMID:23910352
Dormer, Nathan H.; Gupta, Vineet; Scurto, Aaron M.; Berkland, Cory J.; Detamore, Michael S.
In the present study, composite scaffolds made with different weight ratios (0.5:1, 1:1 and 2:1) of bioactive glass (15Ca:80Si:5P) (BG)/polyvinyl alcohol (PVA) (PVABG) and chitosan (Chi)/collagen (Col) (ChiCol) were prepared by three mechanical freeze-thaw followed by freeze-drying to obtain the porous scaffolds. The mechanical properties and the in vitro biocompatibility of the composite scaffolds to simulated body fluid (SBF) and to rat osteoblast-like UMR-106 cells were investigated. The results from the studies indicated that the porosity and compressive strength were controlled by the weight ratio of PVABG:ChiCol. The highest compressive modulus of the composites made was 214.64 MPa which was for the 1:1 weight ratio PVABG:ChiCol. Mineralization study in SBF showed the formation of apatite crystals on the PVABG:ChiCol surface after 7 days of incubation. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the PVABG:ChiCol surface. MTT and ALP tests on the 1:1 weight ratio PVABG:ChiCol composite indicated that the UMR-106 cells were viable. Alkaline phosphatase activity was found to increase with increasing culturing time. In addition, we showed the potential of PVABG:ChiCol drug delivery through PBS solution studies. 81.14% of BSA loading had been achieved and controlled release for over four weeks was observed. Our results indicated that the PVABG:ChiCol composites, especially the 1:1 weight ratio composite exhibited significantly improved mechanical, mineral deposition, biological properties and controlled release. This made them potential candidates for bone tissue engineering applications. PMID:24656353
Pon-On, Weeraphat; Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Tang, I-Ming
Biocompatibility of a porous alumina ceramic scaffold coated with hydroxyapatite and bioglass.
This study aimed to evaluate the osteointegration and genotoxic potential of a bioactive scaffold, composed of alumina and coated with hydroxyapatite and bioglass, after their implantation in tibias of rats. For this purpose, Wistar rats underwent surgery to induce a tibial bone defect, which was filled with the bioactive scaffolds. Histology analysis (descriptive and morphometry) of the bone tissue and the single-cell gel assay (comet) in multiple organs (blood, liver, and kidney) were used to reach this aim after a period of 30, 60, 90, and 180 days of material implantation. The main findings showed that the incorporation of hydroxyapatite and bioglass in the alumina scaffolds produced a suitable environment for bone ingrowth in the tibial defects and did not demonstrate any genotoxicity in the organs evaluated in all experimental periods. These results clearly indicate that the bioactive scaffolds used in this study present osteogenic potential and still exhibit local and systemic biocompatibility. These findings are promising once they convey important information about the behavior of this novel biomaterial in biological system and highlight its possible clinical application. PMID:23894045
Kido, Hueliton Wilian; Ribeiro, Daniel Araki; de Oliveira, Poliani; Parizotto, Nivaldo Ant¶nio; Camilo, Claudia Cristiane; Fortulan, Carlos Alberto; Marcantonio, Elcio; da Silva, Victor Hugo Pereira; Renno, Ana Claudia Muniz
Polyurethane-based scaffolds for myocardial tissue engineering.
Bi-layered scaffolds with a 0░/90░ lay-down pattern were prepared by melt-extrusion additive manufacturing (AM) using a poly(ester urethane) (PU) synthesized from poly(?-caprolactone) diol, 1,4-butandiisocyanate and l-lysine ethyl ester dihydrochloride chain extender. Rheological analysis and differential scanning calorimetry of the starting material showed that compression moulded PU films were in the molten state at a higher temperature than 155░C. The AM processing temperature was set at 155░C after verifying the absence of PU thermal degradation phenomena by isothermal thermogravimetry analysis and rheological characterization performed at 165░C. Scaffolds highly reproduced computer-aided design geometry and showed an elastomeric-like behaviour which is promising for applications in myocardial regeneration. PU scaffolds supported the adhesion and spreading of human cardiac progenitor cells (CPCs), whereas they did not stimulate CPC proliferation after 1-14 days culture time. In the future, scaffold surface functionalization with bioactive peptides/proteins will be performed to specifically guide CPC behaviour. PMID:24501673
Chiono, Valeria; Mozetic, Pamela; Boffito, Monica; Sartori, Susanna; Gioffredi, Emilia; Silvestri, Antonella; Rainer, Alberto; Giannitelli, Sara Maria; Trombetta, Marcella; Nurzynska, Daria; Di Meglio, Franca; Castaldo, Clotilde; Miraglia, Rita; Montagnani, Stefania; Ciardelli, Gianluca
Monosaccharides as Scaffolds for the Synthesis of Novel Compounds
NASA Astrophysics Data System (ADS)
This chapter focuses on monosaccharides and scaffolds their derivatives as scaffolds for the synthesis of primarily bioactive compounds. Such carbohydrate derivatives have been designed to modulate mainly protein-protein and peptide-protein interactions although modulators of carbohydrate-protein and carbohydrate-nucleic acid interactions have also been of interest. The multiple hydroxyl groups that are present on saccharides have made pyranose, furanose and iminosugars ideal templates or scaffolds to which recognition or pharmacophoric groups can be grafted to generate novel compounds for medicinal chemistry. The synthesis of compounds for evaluations require strategies for regioselective reactions of saccharide hydroxyl groups and use of orthogonally stable protecting groups. Syntheses have been carried out on the solid phase and in solution. Also the use of uronic acids, amino sugars and sugar amino acids has facilitated the synthesis of peptidomimetics and prospecting libraries as they enable, through presence of amino or carboxylic acid groups, chemoselective approaches to be employed in solution and on solid phase. Sugar amino acids are readily incorporated, as peptide isosteres, to generate sugar-peptide hybrids or for the synthesis of novel carbopeptoids . The synthesis of new cyclic compounds, derived in part from saccharides, and their application as scaffolds is an emerging area and recent examples include spirocyclic compounds, benzodiazepine-saccharide hybrids and macrolide-saccharide hybrids. Potent bioactive saccharide derivatives have been identified that include enzyme inhibitors , somatostatin receptor ligands, integrin ligands, anti-viral compounds, shiga toxin inhibitors and cell growth inhibitors. Some saccharide derivatives have demonstrated improved cellular permeability when compared with peptides and are in clinical trials.
Murphy, Paul V.; Velasco-Torrijos, Trinidad
CaO-SiO(2) base glass-matrix/Ti particle biocomposite coatings on Ti6Al4V substrates have been prepared by means of Vacuum Plasma Spray. The base glass is considered bioactive, because, when soaked in a fluid that simulates the inorganic ion concentration of human plasma (SBF), it develops a bonelike apatite layer on its surface. The aim of this research activity was to toughen this brittle bioactive material and to broaden its biomedical applications. Pure titanium was chosen as toughening phase because of its well-known biocompatibility, and Ti6Al4V alloy as substrate because of both its biocompatibility and its mechanical reliability. At first the composites were prepared as bulk materials, by means of a simple sintering process. Then, by ball-milling the sintered composite, the as-obtained "composite powders" were sprayed by Vacuum Plasma Spray (VPS) on the substrate. By means of Differential Thermal Analysis (DTA) and Differential Scanning Calorimetry (DSC), the characteristic temperatures of the base glasses were determined. The thermal properties of mixtures of glass powders and different vol% Ti particles were studied by means of DTA, DSC, hot-stage microscopy, and dilatometry, with the aim of optimizing the sintering conditions. Both the bulk and the coated samples have been characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), compositional analysis (EDS), Vickers indentations, and leaching tests after soaking in a simulated body fluid (SBF). PMID:10898882
Vernķ, E; Brovarone, C V; Milanese, D
Biodegradable Polylactic Acid (PLA) Microstructures for Scaffold Applications
In this research, we present a simple and cost effective soft lithographic process to fabricate PLA scaffolds for tissue engineering. In which, the negative photoresist JSR THB-120N was spun on a glass subtract followed by conventional UV lithographic processes to fabricate the master to cast the PDMS elastomeric mold. A thin poly(vinyl alcohol) (PVA) layer was used as a mode release such that the PLA scaffold can be easily peeled off. The PLA precursor solution was then cast onto the PDMS mold to form the PLA microstructures. After evaporating the solvent, the PLA microstructures can be easily peeled off from the PDMS mold. Experimental results show that the desired microvessels scaffold can be successfully transferred to the biodegradable polymer PLA.
Wang, G -J; Hsueh, C -C
Broad spectrum bioactive sunscreens.
The development of sunscreens containing reduced concentration of chemical UV filters, even though, possessing broad spectrum effectiveness with the use of natural raw materials that improve and infer UV absorption is of great interest. Due to the structural similarities between polyphenolic compounds and organic UV filters, they might exert photoprotection activity. The objective of the present research work was to develop bioactive sunscreen delivery systems containing rutin, Passiflora incarnata L. and Plantago lanceolata extracts associated or not with organic and inorganic UV filters. UV transmission of the sunscreen delivery system films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection efficacy was evaluated according to the following parameters: estimated sun protection factor (SPF); Boot's Star Rating category; UVA/UVB ratio; and critical wavelength (lambda(c)). Sunscreen delivery systems obtained SPF values ranging from 0.972+/-0.004 to 28.064+/-2.429 and bioactive compounds interacted with the UV filters positive and negatively. This behavior may be attributed to: the composition of the delivery system; the presence of inorganic UV filter and quantitative composition of the organic UV filters; and the phytochemical composition of the P. incarnata L. and P. lanceolata extracts. Among all associations of bioactive compounds and UV filters, we found that the broad spectrum sunscreen was accomplished when 1.68% (w/w) P. incarnata L. dry extract was in the presence of 7.0% (w/w) ethylhexyl methoxycinnamate, 2.0% (w/w) benzophenone-3 and 2.0% (w/w) TiO(2). It was demonstrated that this association generated estimated SPF of 20.072+/-0.906 and it has improved the protective defense against UVA radiation accompanying augmentation of the UVA/UVB ratio from 0.49 to 0.52 and lambda(c) from 364 to 368.6nm. PMID:18662760
Velasco, Maria Valķria Robles; Sarruf, Fernanda Daud; Salgado-Santos, Idalina Maria Nunes; Haroutiounian-Filho, Carlos Alberto; Kaneko, Telma Mary; Baby, Andrķ Rolim
Porous scaffolds consisting of bioactive inorganic nanoparticles and biodegradable polymers have gained much interest in bone tissue engineering. We report here a facile approach to fabricating poly(l-lactic acid)-grafted hydroxyapatite (g-HAp)/poly(lactide-co-glycolide) (PLGA) nanocomposite (NC) porous scaffolds by solvent evaporation of Pickering high internal phase emulsion (HIPE) templates, where g-HAp nanoparticles act as particulate stabilizers. The resultant porous scaffolds exhibit an open and rough pore structure. The pore structure and mechanical properties of the scaffolds can be tuned readily by varying the g-HAp nanoparticle concentration and internal phase volume fraction of the emulsion templates. With increasing the g-HAp concentration or decreasing the internal phase volume fraction, the pore size and the porosity decrease, while the Young's modulus and the compressive stress enhance. Moreover, the in vitro mineralization tests show that the bioactivity of the scaffolds increases with increasing the g-HAp concentration. Furthermore, the anti-inflammatory drug ibuprofen (IBU) is loaded into the scaffolds, and the drug release studies indicate that the loaded-IBU exhibits a sustained release profile. Finally, in vitro cell culture assays prove that the scaffolds are biocompatible because of supporting adhesion, spreading, and proliferation of mouse bone mesenchymal stem cells. All the results indicate that the solvent evaporation based on Pickering HIPE templates is a promising alternative method to fabricate NC porous scaffolds for potential bone tissue engineering applications. PMID:25243730
Hu, Yang; Gu, Xiaoyu; Yang, Yu; Huang, Jian; Hu, Meng; Chen, Weike; Tong, Zhen; Wang, Chaoyang
Development of a Multi-Functional Biopolymer Scaffold for Neural Tissue Engineering
NASA Astrophysics Data System (ADS)
Spinal cord injury (SCI) affects approximately 270,000 people in the U.S., with approximately 12,000 new cases occurring every year. Several strategies have been investigated to enhance axonal regeneration after SCI, however, the resulting growth can be random and disorganized. Bioengineered scaffolds provide a physical substrate for the guidance of regenerating axons towards their targets, and can be produced by freeze casting. This technique involves the controlled directional solidification of an aqueous solution or suspension, resulting in a linearly aligned porous structure caused by ice templating. In this thesis, freeze casting was used to create novel porous chitosan-alginate (C/A) scaffolds with longitudinally aligned channels and a compressive modulus (5.08 ▒ 0.61 kPa) comparable to that of native spinal cord tissue. These C/A scaffolds supported the viability, attachment, and directionally oriented growth of chick dorsal root ganglia (DRG) neurites in vitro, with surface adsorptions of polycations and laminin promoting significantly longer neurite growth than the uncoated scaffolds (p<0.001). In order to integrate therapeutic biomolecules within the scaffolds for sustained release, alginate and chitosan microcapsules produced by spray drying were used to encapsulate brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), and the enzyme chondroitinase ABC (chABC) prior to scaffold incorporation. BDNF and NT-3 were released from the C/A scaffolds in a sustained manner for 8 weeks in vitro, while chABC was released for up to 35 days. However, up to 85% of biomolecules emained entrapped within the scaffold walls, due to limitation of diffusion by the scaffold wall mesh size. Release of bioactive chABC and neurotrophins from the multifunctional scaffolds promoted the growth of DRG neurites through an in vitro barrier of chondroitin sulfate proteoglycans, a main inhibitory component of the growth-inhibiting glial scar in the injured spinal cord. The present data suggest these multi-functional scaffolds are suitable for use and future testing in vivo as a combination strategy for spinal cord repair due to their ability to promote the directionally oriented growth of neurites and their ability to provide the sustained release of therapeutic bioactive molecules for the stimulation of axonal growth through the glial scar.
Francis, Nicola Louise
Bioactive natural products and chirality.
Mori's synthetic works on bioactive natural products in general and pheromones in particular started about 40 years ago to establish their absolute configurations and also to clarify their stereochemistry-bioactivity relationships. Results indicate that bioactive natural products are not always enantiomerically pure, and the stereochemistry-bioactivity relationships are not simple but complicated. For example, neither (R)- nor (S)-sulcatol, the aggregation pheromone of an ambrosia beetle, is behaviorally bioactive, whereas their mixture is active. In the case of olean, the sex pheromone of the olive fruit fly, its (R)-isomer is active against the males and the (S)-isomer is active against the females. Recent synthesis of two new insect pheromones is discussed to illustrate the modern methods in enantioselective synthesis. PMID:21633977
Mori, Kenji
The hitherto inconsistency in clinical performance for engineered skin drives the current development of novel cell-scaffolding materials; one challenge is to only extract essential characteristics from the complex native ECM (extracellular matrix) and incorporate them into a scaffold with minimal complexity to support normal cell functions. This study involved small-molecule-based bioactive hydrogels produced by the co-assembly of two aromatic peptide amphiphiles: Fmoc-FF (Fluorenylmethoxycarbonyl-diphenylalanine) and Fmoc-RGD (arginine-glycine-aspartic acid). Three-dimensionally cultured human dermal fibroblasts deposited dense ECM networks including fibronectin and collagen I within the hydrogels in a 14-day culture. The fibroblasts organized the fibrous ECM and contracted the gel without differentiating into myofibroblasts. The stiffness of the cell-gel constructs increased dramatically due to ECM formation and gel contraction. This created an economical biomimetic model-scaffold to further understand skin reconstruction in vitro and supplied a design pathway to create versatile cell-scaffolds with varied bioactivities and simplicity. PMID:24812581
Zhou, Mi; Ulijn, Rein V; Gough, Julie E
Development of bioactive porous ?-TCP/HAp beads for bone tissue engineering.
Porous beads of bioactive ceramics such as hydroxyapatite (HAp) and tribasic calcium phosphate (TCP) are considered a promising scaffold for cultivating bone cells. To realize this, ?-TCP/HAp functionally graded porous beads are fabricated with two main purposes: to maintain the function of the scaffold with sufficient strength up to the growth of new bone, and is absorbed completely after the growth. HAp is a bioactive material that has both high strength and strong tissue-adhesive properties, but is not readily absorbed by the human body. On the contrary, ?-TCP is highly bioabsorbable, resulting in a scaffold that is absorbed before it is completely replaced by bone. In this study, we produced porous, bead-shaped carriers as scaffolds for osteoblast culture. To control the solubility in vivo, the fabricated beads contained ?-TCP at the center and HAp at the surface. Cell adaptability of these beads for bone tissue engineering was confirmed in vitro. It was found that ?-TCP/HAp bead carriers exhibit low toxicity in the initial stages of cell seeding and cell adhesion. The presence of HAp in the composite bead form effectively increased ALP activity. In conclusion, it is suggested that these newly developed ?-TCP/HAp beads are a promising tool for bone tissue engineering. PMID:23983180
Asaoka, Teruo; Ohtake, Shoji; Furukawa, Katsuko S; Tamura, Akito; Ushida, Takashi
The hitherto inconsistency in clinical performance for engineered skin drives the current development of novel cell-scaffolding materials; one challenge is to only extract essential characteristics from the complex native ECM (extracellular matrix) and incorporate them into a scaffold with minimal complexity to support normal cell functions. This study involved small-molecule-based bioactive hydrogels produced by the co-assembly of two aromatic peptide amphiphiles: Fmoc-FF (Fluorenylmethoxycarbonyl-diphenylalanine) and Fmoc-RGD (arginine¢glycine¢aspartic acid). Three-dimensionally cultured human dermal fibroblasts deposited dense ECM networks including fibronectin and collagen I within the hydrogels in a 14-day culture. The fibroblasts organized the fibrous ECM and contracted the gel without differentiating into myofibroblasts. The stiffness of the cell-gel constructs increased dramatically due to ECM formation and gel contraction. This created an economical biomimetic model-scaffold to further understand skin reconstruction in vitro and supplied a design pathway to create versatile cell-scaffolds with varied bioactivities and simplicity. PMID:24812581
Zhou, Mi; Ulijn, Rein V
Calcium phosphate invert glasses with soda and titania
Calcium phosphate glasses in the pyrophosphate region were obtained by addition of Na2O and TiO2. The glasses with CaO content of ?55 mol% contain pyrophosphate and orthophosphate groups without metaphosphate by Raman and NMR observation. Crystalline phases with bioactivity such as ?-Ca3(PO4)2 and\\/or ?-Ca2P2O7 were precipitated in the glasses at 850░C. Some of the glasses can be sintered at 850░C,
Toshihiro Kasuga; Yoshihiro Abe
Poly(?-caprolactone) (PCL) has received considerable attention in bone tissue engineering. However, the lack of osteoinductive ability of PCL limits its application. The aim of this study was to directly attach bone morphogenetic protein-2 (BMP-2) to PCL scaffolds by a crosslinking conjugation method and to investigate whether the bound BMP-2 maintained bioactivity in vitro. Immunofluorescent staining against BMP-2 and quantitative enzyme-linked immunosorbent assay measurements demonstrated that BMP-2 was successfully immobilized on the PCL three-dimensional scaffold by aminolysis and subsequent chemical conjugation. Conjugation produced much higher immobilization efficiency than the physical adsorption. Conjugated BMP-2 release from the PCL scaffolds was significantly slower than that from BMP-2-adsorbed PCL scaffolds over 15 days, which resulted in more BMP-2 locally retained on the conjugated scaffold. Further, the downstream Smads pathway was upregulated in bone marrow stromal cells cultured on the BMP-2-conjugated PCL scaffolds. Finally, gene expression of osteogenic markers (alkaline phosphatase, osteoclacin, and type I collagen) was upregulated in bone marrow stromal cells cultured on the PCL scaffolds with BMP-2 conjugation, but not on PCL scaffolds after BMP-2 adsorption. Therefore, our finding demonstrated that BMP-2 conjugation on polyester scaffolds is a feasible way to impart scaffolds with osteoinductive capability. PMID:20560772
Zhang, Huina; Migneco, Francesco; Lin, Chia-Ying; Hollister, Scott J
Bone tissue engineering requires an osteoconductive scaffold, multipotent cells with regenerative capacity and bioactive molecules. In this study we investigated the osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) on titanium dioxide (TiO2) scaffold coated with alginate hydrogel containing various concentrations of simvastatin (SIM). The mRNA expression of osteoblast-related genes such as collagen type I alpha 1 (COL1A1), alkaline phosphatase (ALPL), osteopontin (SPP1), osteocalcin (BGLAP) and vascular endothelial growth factor A (VEGFA) was enhanced in hAD-MSCs cultured on scaffolds with SIM in comparison to scaffolds without SIM. Furthermore, the secretion of osteoprotegerin (OPG), vascular endothelial growth factor A (VEGFA), osteopontin (OPN) and osteocalcin (OC) to the cell culture medium was higher from hAD-MSCs cultured on scaffolds with SIM compared to scaffolds without SIM. The TiO2 scaffold coated with alginate hydrogel containing SIM promote osteogenic differentiation of hAD-MSCs in vitro, and demonstrate feasibility as scaffold for hAD-MSC based bone tissue engineering. PMID:24704451
Pullisaar, Helen; Reseland, Janne E; Haugen, HÕvard J; Brinchmann, Jan E; Ostrup, Esben
RNA interference (RNAi) is a promising approach for cancer treatment. Site specific and controlled delivery of RNAi could be beneficial to the patient, while at the same time reducing undesirable off-target side effects. We utilized electrospinning to generate a biodegradable scaffold capable of incorporating and delivering a bioactive plasmid encoding for short hairpin (sh) RNA against the cell cycle specific protein, Cdk2. Three electrospun scaffolds were constructed, one using polycaprolactone (PCL) alone (Control) and PCL with plasmid DNA encoding for either Cdk2 (Cdk2i) and EGFP (EGFPi, also served as a control) shRNA. Scaffold fiber diameters ranged from 1 to 20 Ąm (DNA containing) and 0.2¢3 Ąm (Control). While the electrospun fibers remained intact for more than two weeks in physiological buffer, degradation was visible during the third week of incubation. Approximately 20¢60 ng/ml (?2.5% cumulative release) of intact and bioactive plasmid DNA was released over 21 days. Further, Cdk2 mRNA expression in cells plated on the Cdk2i scaffold was decreased by ?51% and 30%, in comparison with that of cells plated on Control or EGFPi scaffold, respectively. This decrease in Cdk2 mRNA by the Cdk2i scaffold translated to a ?40% decrease in the proliferation of the breast cancer cell line, MCF-7, as well as the presence of increased number of dead cells. Taken together, these results represent the first successful demonstration of the delivery of bioactive RNAi-based plasmid DNA from an electrospun polymer scaffold, specifically, in disrupting cell cycle regulation and suppressing proliferation of cancer cells. PMID:23285007
Achille, Clement; Sundaresh, Sowmya; Chu, Benjamin; Hadjiargyrou, Michael
Scaffolding in Technology-Enhanced Science Education
This dissertation focuses on the effectiveness of scaffolding in technology-enhanced science learning environments, and specifically the relative merits of computer- and teacher-based scaffolding in science inquiry. Scaffolding is an instructional...
Wu, Hui-Ling
Three-dimensional (3D) scaffolds, which are bioactive and aid in neuronal guidance, are essential in the repair and regeneration of injured peripheral nerves. In this study, we used novel inorganic microfibres guided by phosphate glass (PG). PG fibres (PGfs) were aligned on compressed collagen that was rolled into a nerve conduit. In vitro tests confirmed that adult dorsal root ganglion (DRG) neurons showed active neurite outgrowth along the fibres, with a maximum number and length of neurites being significantly higher than those cultured on tissue culture plastic. In vivo experiments with nerve conduits that either contained PGfs (PGf/Col) or lacked them (Col) were conducted on transected sciatic nerves of rats for up to 12?weeks. One week after implantation, the PGf/Col group showed many axons extending along the scaffold, whereas the Col group showed none. Eight weeks after implantation, the PGf/Col group exhibited greater recovery of plantar muscle atrophy than the Col group. Electrophysiological studies revealed that some animals in the PGf/Col group at 6 and 7?weeks post-implantation (5.3% and 15.8%, respectively) showed compound muscle action potential. The Col group over the same period showed no response. Motor function also showed faster recovery in the PGf/Col group compared to the Col group up to 7?weeks. However, there was no significant difference in the number of axons, muscle atrophy or motor and sensory functions between the two groups at 12?weeks post-implantation. In summary, phosphate glass fibres can promote directional growth of axons in cases of peripheral nerve injury by acting as physical guides. Copyright ® 2012 John Wiley & Sons, Ltd. PMID:23038678
Kim, Young-Phil; Lee, Gil-Su; Kim, Jong-Wan; Kim, Min Soo; Ahn, Hong-Sun; Lim, Jae-Young; Kim, Hae-Won; Son, Young-Jin; Knowles, Jonathan C; Hyun, Jung Keun
The drug release study of ceftriaxone from porous hydroxyapatite scaffolds.
Hydroxyapatite (HAP) is an important biomedical material that is used for grafting osseous defects. It has an excellent bioactivity and biocompatibility properties. To isolate hydroxyapatite, pieces of cleaned cattle's bone were heated at different temperature range from 400 degrees C up to 1,200 degrees C. A reasonable yield of 60.32% w/w HAP was obtained at temperature range from 1,000 degrees C to 1,200 degrees C. Fourier transform infrared spectra and the thermogravimetric measurement showed a clear removal of organic at 600 degrees C as well as an excellent isolation of HAP from the bones which was achieved at 1,000-1,200 degrees C. This was also confirmed from X-ray diffraction of bone sample heated at 1,200 degrees C. The concentration ions were found to be sodium, potassium, lithium, zinc, copper, iron, calcium, magnesium, and phosphate present in bones within the acceptable limits for its role in the bioactivity property of HAP. Glucose powder was used as a porosifier. Glucose was novel and excellent as porogen where it was completely removed by heating, giving an efficient porosity in the used scaffolds. The results exhibited that the ceftriaxone drug release was increased with increasing the porosity. It was found that a faster, higher, and more regular drug release was obtained from the scaffold with a porosity of 10%. PMID:19499343
Al-Sokanee, Zeki N; Toabi, Abedl Amer H; Al-Assadi, Mohammed J; Alassadi, Erfan A S
The fabrication of 3-dimensional (3D) tissue scaffolds is a competitive approach to engineered tissues. An ideal tissue scaffold must be highly porous, biocompatible, biodegradable, easily processed and cost-effective, and have adequate mechanical properties. A casting based process has been developed in this study to fabricate 3D alginate tissue scaffolds. The alginate\\/calcium gluconate hydrogel was quenched in a glass mold and
W. M. Parks; Y. B. Guo
Scaffolds that not only mimic the mechanical and structural properties of the target tissue but also support cell survival/growth are likely necessary for the development of mechanically functional cardiovascular tissues. To reach these goals, we have generated scaffolds that are elastic to approximate soft tissue mechanical properties, are nanofibrous to mimic fibrous nature of extracellular matrix (ECM), have aligned structure to guide cellular alignment, and are capable of releasing insulin-like growth factor (IGF-1) to administrate cellular growth and survival. We have developed a technique that can quickly fabricate (<3 h) such scaffolds by simultaneously electrospinning elastase-sensitive polyurethaneurea nanofibers, encapsulating IGF-1 into poly(lactide-co-glycolide) (PLGA) microspheres and assembling them into scaffolds. Scaffold morphology, mechanical properties, degradation with or without elastase, and bioactivity of the released IGF-1 were assessed. The scaffolds had degree of alignment approximately 70%. They were flexible and relatively strong, with tensile strengths of 3.4-11.1 MPa, elongations at break of 71-88%, and moduli of 2.3-7.9 MPa at the alignment direction. IGF-1 release profile and bioactivity were dependent on PLGA content and molecular weight and IGF-1 loading. The released IGF-1 remained bioactive for 4 weeks. The fabricated nanofibers were elastase-sensitive with weight remaining <59% after a 4-week degradation in the presence of elastase. Mesenchymal stem cells (MSCs) were seeded on the scaffolds and cultured either under normal culture conditions (21% O(2), 5% CO(2), and 20% fetal bovine serum (FBS)) or hypoxia/nutrient starvation conditions (5% O(2), 5% CO(2), and 1% FBS) to evaluate the effect of IGF-1 loading on cell growth and survival. Under normal culture conditions, MSCs were found to align on the scaffolds with a degree of alignment matching that of the scaffold. The IGF-1 loaded scaffolds enhanced MSC growth during a 7-day culture period, with higher IGF-1 content showing better stimulus effect. Under hypoxia/nutrient starvation conditions, the IGF-1 loaded scaffolds were found to significantly improve MSC survival. PMID:19689108
Wang, Feng; Li, Zhenqing; Tamama, Kenichi; Sen, Chandan K; Guan, Jianjun
Polymer and ceramic composite scaffolds play a crucial role in bone tissue engineering. In an attempt to mimic the architecture of natural extracellular matrix (ECM), poly(l-lactic acid)/?-tricalcium phosphate (PLLA/?-TCP) nanocomposite scaffolds with a hierarchical pore structure were fabricated by combining thermal induced phase separation and salt leaching techniques. The nanocomposite scaffold consisted of a nanofibrous PLLA matrix with a highly interconnected, high porosity (>93%) hierarchical pore structure with pore diameters ranging from 500nm to 300?m and a homogeneously distributed ?-TCP nanoparticle phase. The nanofibrous PLLA matrix had a fiber diameter of 70-300nm. The nanocomposite scaffolds possess three levels of hierarchical structure: (1) porosity; (2) nanofibrous PLLA struts comprising the pore walls; and (3) ?-TCP nanoparticle phase. The ?-TCP nanoparticle phase improved the mechanical properties and bioactivity of the PLLA matrix. The nanocomposite scaffolds supported MG-63 osteoblast proliferation, penetration, and ECM deposition, indicating the potential of PLLA/?-TCP nanocomposite scaffolds with hierarchical porosity for bone tissue engineering applications. PMID:24933519
Lou, Tao; Wang, Xuejun; Song, Guojun; Gu, Zheng; Yang, Zhen
NASA Astrophysics Data System (ADS)
Bone is the second most commonly transplanted tissue in the United States. Limitations of current bone defect treatment options include morbidity at the autograft harvest site, mechanical failure, and poorly controlled growth factor delivery. Combining synthetic scaffolds with biologics may address these issues and reduce dependency on autografts. The ideal scaffolding system should promote tissue in-growth and nutrient diffusion, control delivery of biologics and maintain mechanical integrity during bone formation. This dissertation evaluates how scaffold permeability, conjugated bone morphogenetic protein-2 (BMP-2) and differentiation medium affect osteogenesis in vitro and bone growth in vivo.. "High" and "low" permeability polycaprolactone (PCL) scaffolds with regular architectures were manufactured using solid free form fabrication. Bone growth in vivo was evaluated in an ectopic mouse model. High permeability scaffolds promoted better 8 week bone growth, supported tissue penetration into the scaffold core, and demonstrated increased mechanical properties due to newly formed bone. Next, the effects of differentiation medium and conjugated BMP-2 on osteogenesis were compared. Conjugation may improve BMP-2 loading efficiency, help localize bone growth and control release. High permeability scaffolds were conjugated with BMP-2 using the crosslinker, sulfo-SMCC. When adipose-derived and bone marrow stromal cells were seeded onto constructs (with or without BMP-2), BMSC expressed more differentiation markers, and differentiation medium affected differentiation more than BMP-2. In vivo, scaffolds with ADSC pre-differentiated in osteogenic medium (with and without BMP-2) and scaffolds with only BMP-2 grew the most bone. Bone volume did not differ among these groups, but constructs with ADSC had evenly distributed, scaffold-guided bone growth. Analysis of two additional BMP-2 attachment methods (heparin and adsorption) showed highest conjugation efficiency for the sulfo-SMCC method. BMP-2 release from all constructs was minimal, proving that BMP-2 was tightly bound to constructs regardless of the attachment method. However, C2C12 myoblasts did not produce alkaline phosphatase when seeded onto heparin- and sulfo-SMCC-conjugated scaffolds suggesting hindrance of BMP-2 bioactivity. This thesis demonstrated that high permeability PCL scaffolds promote bone growth better than low permeability scaffolds and that in vitro pre-differentiation of cells affects osteogenesis more than conjugated BMP-2. Future work will optimize BMP-2 conjugation to ensure maintenance of bioactivity.
Mitsak, Anna Guyer
Scaffold-hopping potential of fragment-based de novo design: the chances and limits of variation.
The identification of new lead structures is a pivotal task in early drug discovery. Molecular de novo design of ligand structures has been successfully applied in various drug discovery projects. Still, the question of the scaffold hopping potential of drug design by adaptive evolutionary optimization has been left unanswered. It was unclear whether de novo design is actually able to leap away from given chemotypes ("activity islands"), allowing for rescaffolding of compounds. We have addressed these questions by scrutinizing different scoring functions of our de novo design software Flux for their ability to enable scaffold-hops for various target classes. We evaluated both the potential bioactivity and the scaffold diversity of de novo generated structures. For several target classes, known lead structures were reconstructed by the de novo algorithm ("lead-hopping"). We demonstrate that for one or multiple templates of a given chemotype, other chemotypes are reached during de novo compound generation, thus indicating successful scaffold-hops. PMID:19442066
Krueger, Bjoern A; Dietrich, Axel; Baringhaus, Karl-Heinz; Schneider, Gisbert
Healing properties of surface-coated polycaprolactone-co-lactide scaffolds: a pilot study in sheep.
The aim of this pilot study was to evaluate the bioactive, surface-coated polycaprolactone-co-lactide scaffolds as bone implants in a tibia critical size defect model. Polycaprolactone-co-lactide scaffolds were coated with collagen type I and chondroitin sulfate and 30 piled up polycaprolactone-co-lactide scaffolds were implanted into a 3?cm sheep tibia critical size defect for 3 or 12 months (n?=?5 each). Bone healing was estimated by quantification of bone volume in the defects on computer tomography and microcomputer tomography scans, plain radiographs, biomechanical testing as well as by histological evaluations. New bone formation occurred at the proximal and distal ends of the tibia in both groups. The current pilot study revealed a mean new bone formation of 63% and 172% after 3 and 12 months, respectively. The bioactive, surface coated, highly porous three-dimensional polycaprolactone-co-lactide scaffold stack itself acted as a guide rail for new bone formation along and into the implant. These preliminary data are encouraging for future experiments with a larger group of animals. PMID:23413230
Rentsch, Claudia; Schneiders, Wolfgang; Hess, Ricarda; Rentsch, Barbe; Bernhardt, Ricardo; Spekl, Kathrin; Schneider, Konrad; Scharnweber, Dieter; Biewener, Achim; Rammelt, Stefan
NSDL National Science Digital Library
Protein kinase cascades are a reoccurring feature of signal transduction pathways. Recent investigations have focused on how kinase-scaffolding proteins help to convert a graded stimulus into a switch-like or binary response. New findings reveal that the graded-to-binary conversion can be turned on or off, depending on the location of the scaffold within the cell.
Henrik G. Dohlman (Chapel Hill;University of North Carolina REV)
Elastin-Coated Biodegradable Photopolymer Scaffolds for Tissue Engineering Applications
One of the main open issues in modern vascular surgery is the nonbiodegradability of implants used for stent interventions, which can lead to small caliber-related thrombosis and neointimal hyperplasia. Some new, resorbable polymeric materials have been proposed to substitute traditional stainless-steel stents, but so far they were affected by poor mechanical properties and low biocompatibility. In this respect, a new material, polypropylene fumarate (PPF), may be considered as a promising candidate to implement the development of next generation stents, due to its complete biodegradability, and excellent mechanical properties and the ease to be precisely patterned. Besides all these benefits, PPF has not been tested yet for vascular prosthesis, mainly because it proved to be almost inert, while the ability to elicit a specific biological function would be of paramount importance in such critical surgery applications. Here, we propose a biomimetic functionalization process, aimed at obtaining specific bioactivation and thus improved cell-polymer interaction. Porous PPF-based scaffolds produced by deep-UV photocuring were coated by elastin and the functionalized scaffolds were extensively characterized, revealing a stable bound between the protein and the polymer surface. Both 3T3 and HUVEC cell lines were used for in vitro tests displaying an enhancement of cells adhesion and proliferation on the functionalized scaffolds. PMID:25405204
Barenghi, Rossella; Beke, Szabolcs; Gavazzo, Paola; Farkas, Balßzs; Scaglione, Silvia
Classification of Scaffold Hopping Approaches
The general goal of drug discovery is to identify novel compounds that are active against a preselected biological target with acceptable pharmacological properties defined by marketed drugs. Scaffold hopping has been widely applied by medicinal chemists to discover equipotent compounds with novel backbones that have improved properties. In this review, scaffold hopping is classified into four major categories, namely heterocycle replacements, ring opening or closure, peptidomimetics, and topology-based hopping. The structural diversity of original and final scaffolds with respect to each category will be reviewed. The advantages and limitations of small, medium, and large-step scaffold hopping will also be discussed. Software that is frequently used to facilitate different kinds of scaffold hopping methods will be summarized. PMID:22056715
Sun, Hongmao; Tawa, Gregory; Wallqvist, Anders
To date, most interfacial tissue engineering approaches have utilized stratified designs, in which there are two or more discrete layers comprising the interface. Continuously-graded interfacial designs, where there is no discrete transition from one tissue type to another, are gaining attention as an alternative to stratified designs. Given that osteochondral regeneration holds the potential to enhance cartilage regeneration by leveraging the healing capacity of the underlying bone, we endeavored to introduce a continuously graded approach to osteochondral regeneration. The purpose of this study was thus to evaluate the performance of a novel gradient-based scaffolding approach to regenerate osteochondral defects in the New Zealand White rabbit femoral condyle. Bioactive plugs were constructed from poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres with a continuous gradient transition between cartilage-promoting and bone-promoting growth factors. At six and 12 weeks of healing, results suggested that the implants provided support for the neo-synthesized tissue, and the gradient in bioactive signaling may have been beneficial for bone and cartilage regeneration compared to the blank control implant, as evidenced by histology. In addition, the effects of pre-seeding gradient scaffolds with umbilical cord mesenchymal stromal cells (UCMSCs) from the WhartonÆs jelly of New Zealand White rabbits were evaluated. Results indicated that there may be regenerative benefits to pre-localizing UCMSCs within scaffold interiors. The inclusion of bioactive factors in a gradient-based scaffolding design is a promising new treatment strategy for defect repair in the femoral condyle. PMID:22009693
Dormer, Nathan H.; Singh, Milind; Zhao, Liang; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.
Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) through 10-hydroxy-8-octadecenoic acid, and racinoleic acid to 7,10,12-trihydroxy-8-octadecenoic acid. DOD showed antibacterial activity including against food-borne pathogens. Bacillus megaterium ALA2 converted n-6 and n-3 PUFAs to many new oxygenated fatty acids. For example: linoleic acid was converted to12,13-epoxy-9-octadecenoic acid and then to 12,13-dihydroxy-9-octadecenoic acid (12,13-DHOA). From here, there are two bioconversion pathways. The major pathway is: 12,13-DHOA --> 12,13,17-trihydroxy-9(S)-octadecenoic acid (THOA) --> 12,17;13,17-diepoxy-16-hydroxy-9(Z)-octadecenoic acid (DEOA) --> 7-hydroxy-DEOA. The minor pathway is: 12,13-DHOA --> 12,13,16-THOA --> 12-hydroxy-13,16-epoxy-9(Z)-octadecenoic acid. 12,13,17-THOA has anti-plant pathogenic fungal activity. The tetrahydrofuranyl moiety is known in anti cancer drugs. Strain ALA2 also converts other n-3 and n-6 PUFAs such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) to many new oxygenated unsaturated fatty acid products. All of these new products have high potential for antimicrobial agents or biomedical applications. We also screened 12 Mortierella fungal strains from the ARS Culture Collection for the production of bioactive fatty acids such as dihomo-gama-linolenic acid (DGLA) and arachidonic acid. All of the strains tested produced AA and DGLA from glucose or glycerol. The top five AA producers (mg AA/g CDW) were in the following order: M. alpina > M. zychae > M. hygrophila > M. minutissima > M. parvispora. Both AA and DGLA are important natural precursors of a large family of prostaglandin and thromboxane groups. PMID:18296335
Hou, Ching T
In stem cell-based dental tissue engineering, the goal is to create tooth-like structures using scaffold materials to guide the dental stem cells. In this study, the effect of fiber alignment and hydroxyapatite content in biodegradable electrospun PLGA scaffolds have been investigated. Fiber orientation of the scaffolds was random or aligned in bundles. For scaffolds with prefabricated orientation, scaffolds were fabricated from PLGA polymer solution containing 0, 10 or 20 % nano-hydroxyapatite. The scaffolds were seeded with porcine cells isolated from tooth buds (dental mesenchymal, dental epithelial, and mixed dental mesenchymal/epithelial cells). Samples were collected at 1, 3 and 6 weeks. Analyses were performed for cell proliferation, ALP activity, and cell morphology. Fiber alignment showed an effect on cell orientation in the first week after cell seeding, but had no long-term effect on cell alignment or organized calcified matrix deposition once the cells reach confluency. Scaffold porosity was sufficient to allow migration of mesenchymal cells. Hydroxyapatite incorporation did not have a positive effect on cell proliferation, especially of epithelial cells, but seemed to promote differentiation. Concluding, scaffold architecture is important to mesenchymal cell morphology, but has no long-term effect on cell alignment or organized ECM deposition. nHA incorporation does have an effect on cell proliferation, differentiation and ECM production, and should be regarded as a bioactive component of dental bioengineered scaffolds. PMID:23011475
van Manen, Elisabeth H C; Zhang, Weibo; Walboomers, X Frank; Vazquez, Betsy; Yang, Fang; Ji, Wei; Yu, Na; Spear, Daisy J; Jansen, John A; Yelick, Pamela C
The Scaffold Tree ? Visualization of the Scaffold Universe by Hierarchical Scaffold Classification
A hierarchical classification of chemical scaffolds (molecular framework, which is obtained by pruning all terminal side chains) has been introduced. The molecular frameworks form the leaf nodes in the hierarchy trees. By an iterative removal of rings, scaffolds forming the higher levels in the hierarchy tree are obtained. Prioritization rules ensure that less characteristic, peripheral rings are removed first. All
Ansgar Schuffenhauer; Peter Ertl; Silvio Roggo; Stefan Wetzel; Marcus A. Koch; Herbert Waldmann
Hydroxyapatite-reinforced collagen tissue engineering scaffolds
NASA Astrophysics Data System (ADS)
Scaffolds have been fabricated from a wide variety of materials and most have showed some success, either as bone graft substitutes or as tissue engineering scaffolds. However, all current scaffold compositions and architectures suffer from one or more flaws including poor mechanical properties, lack of biological response, nondegradability, or a scaffold architecture not conducive to osteointegration. Biomimetic approaches to scaffold design using the two main components of bone tissue, collagen and hydroxyapatite, resulted in scaffolds with superior biological properties but relatively poor mechanical properties and scaffold architecture. It was hypothesized that by optimizing scaffold composition and architecture, HA-collagen bone tissue engineering scaffolds could provide both an excellent biological response along with improved structural properties. The mechanical properties of freeze-dried HA-collagen scaffolds, the most common type of porous HA-collagen material, were first shown to be increased by the addition of HA reinforcements, but scaffold stiffness still fell far short of the desired range. Based on limitations inherent in the freeze-dried process, a new type of leached-porogen scaffold fabrication process was developed. Proof-of-concept scaffolds demonstrated the feasibility of producing leached-porogen HA-collagen materials, and the scaffold architecture was optimized though careful selection of porogen particle size and shape along with an improved crosslinking technique. The final scaffolds exhibited substantially increased compressive modulus compared to previous types HA-collagen scaffolds, while the porosity, pore size, and scaffold permeability were tailored to be suitable for bone tissue ingrowth. An in vitro study demonstrated the capacity of the leached-porogen scaffolds to serve as a substrate for the differentiation of osteoblasts and subsequent production of new bone tissue. The new leached-porogen scaffold HA-collagen scaffolds were shown to have potential as a highly tailorable bone tissue engineering scaffold with a unique combination of biological, mechanical, and structural properties.
Kane, Robert J.
Poly(l-lactide) (PLLA) microfibrous scaffolds produced by electrospinning were treated with mild Ar or Ar-NH3/H2 plasmas to enhance cell attachment, growth, and infiltration. Goniometry, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS) measurements were used to evaluate the modification of the scaffold surface chemistry by plasma treatment. AFM and XPS measurements showed that both plasma treatments increased the hydrophilicity without affecting the integrity of the fibrous structure and the fiber roughness, whereas Ar-NH3/H2 plasma treatment also resulted in surface functionalization with amine groups. Culture studies of bovine aorta endothelial cells and bovine smooth muscle cells on the plasma-treated PLLA scaffolds revealed that both Ar and Ar-NH3/H2 plasma treatments promoted cell spreading during the initial stage of cell attachment and, more importantly, increased the cell growth rate, especially for Ar plasma treatment. In vitro cell infiltration studies showed that both plasma treatments effectively enhanced cell migration into the microfibrous scaffolds. In vivo experiments involving the subcutaneous implantation of plasma-treated PLLA scaffolds under the skin of Sprague-Dawley rats also showed increased cell infiltration. The results of this study indicate that surface treatment of PLLA microfibrous scaffolds with mild Ar or Ar-NH3/H2 plasmas may have important implications in tissue engineering. Further modifications with bioactive factors should improve the functions of the scaffolds for specific applications. PMID:23281641
Cheng, Qian; Lee, Benjamin Li-Ping; Yan, Zhiqiang; Li, Song
Background Artifical nerve scaffold can be used as a promising alternative to autologous nerve grafts to enhance the repair of peripheral nerve defects. However, current nerve scaffolds lack efficient microstructure and neurotrophic support. Methods Microsphere¢Scaffold composite was developed by incorporating chitosan microspheres loaded with nerve growth factor (NGF¢CMSs) into collagen-chitosan scaffolds (CCH) with longitudinally oriented microchannels (NGF¢CMSs/CCH). The morphological characterizations, in vitro release kinetics study, neurite outgrowth assay, and bioactivity assay were evaluated. After that, a 15-mm-long sciatic nerve gap in rats was bridged by the NGF¢CMSs/CCH, CCH physically absorbed NGF (NGF/CCH), CCH or nerve autograft. 16 weeks after implantation, electrophysiology, fluoro-gold retrograde tracing, and nerve morphometry were performed. Results The NGF¢CMSs were evenly distributed throughout the longitudinally oriented microchannels of the scaffold. The NGF¢CMSs/CCH was capable of sustained release of bioactive NGF within 28 days as compared with others in vitro. In vivo animal study demonstrated that the outcomes of NGF¢CMSs/CCH were better than those of NGF/CCH or CCH. Conclusion Our findings suggest that incorporation of NGF¢CMSs into the CCH may be a promising tool in the repair of peripheral nerve defects. PMID:24983464
Xiao, Wei; Qi, Fengyu; Huang, Jinghui; Luo, Zhuojing
Bioactive response of Ag-doped tape cast Bioglass« 45S5 following heat treatment
The suitability of Bioglass« 45S5 to the tape casting process and the ability of the glass to retain in vitro bioactivity following heat treatment to increase strength has been established. In this research, tape cast Bioglass« was doped with silver prior to heat treatment in an effort to impart antimicrobial properties. The effect of initial dopant concentration and processing temperature
D. C. Clupper; L. L. Hench
Rate of polymer degradation is very important for implantable biomaterials since controlling the degradation rate may complement the biological response and affected mechanical property requirements. In spite of numerous publications on the potential use of combinations of poly lactic acid\\/bioactive glass fillers for degradable bone plate, little information exists on the controlling degradation rate and its effects on the other
A. Zargar Kharazi; M. H. Fathi; F. Bahmani; H. Fanian
Bioactive lipids in metabolic syndrome.
The metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and the precise mechanisms have not been elucidated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. This review explores the physiological functions and molecular actions of bioactive lipids, such as n-3 polyunsaturated fatty acids, conjugated fatty acids, sterols, medium-chain fatty acids, diacylglycerols and phospholipids, in the development of metabolic syndrome. Dietary bioactive lipids suppress the accumulation of abdominal adipose tissue and lipids in the liver and serum, and alleviate hypertension and type 2 diabetes through the transcriptional regulation of lipid and glucose metabolism. Peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins, liver X receptor alpha, retinoid X receptor alpha, farnesoid X receptor alpha, hepatic nuclear factor 4alpha and nuclear factor kappaB contribute to these nuclear actions of bioactive lipids with complex interactions. Recent studies have demonstrated the striking ability of bioactive lipids to regulate the production of physiologically active adipocytokines through PPARgamma activation. In particular, the function of bioactive lipids as dietary adiponectin inducers (dietary insulin sensitizers) deserves attention with respect to alleviation of metabolic syndrome by dietary manipulation. PMID:18177744
Nagao, Koji; Yanagita, Teruyoshi
Somatosensory scaffolding structures
Dynamic changes in somatosensory perception occur as a result of multiple signaling events. In many instances, over-activation of sensory receptors results in the desensitization and subsequent increased threshold for activation of receptors. In other cases, receptor sensitization can occur following tissue injury and/or inflammation. In both cases, signaling mechanisms that control alterations in receptor activities can significantly affect organism response to sensory stimuli, including thermal, mechanical, and chemical. Due to the homeostatic nature of somatosensory recognition, dynamic changes in receptor response can negatively affect an individual's way of life, as well as alert individuals to tissue damage. Here, we will focus on scaffolding structures that regulate somatosensory neuronal excitability. PMID:22291616
Jeske, Nathaniel A.
Porous scaffolds that can prolong the release of bioactive factors are urgently required in bone tissue engineering. In this study, PLGA/gelatin composite microspheres (PGMs) were carefully designed and prepared by entrapping poly(L: -lactide-co-glycolide) (PLGA) microspheres (PMs) in gelatin matrix. By mixing PGMs with PLGA solution directly, drug-loaded PLGA/carbonated hydroxyapatite (HAp)/PGMs composite scaffolds were successfully fabricated. In vitro release of fluorescein isothiocyanate-dextran (FD70S) as a model drug from the scaffolds as well as PMs and PGMs was studied by immersing samples in phosphate buffered saline (pH = 7.4) at 37░C for 32 days. Compared with PMs, PGMs and PLGA/HAp/PGMs scaffolds exhibited slow and steady release behavior with constant release rate and insignificantly original burst release. The swelling of PGMs, diffusion of drugs, and degradation of polymer dominated the release behaviors synergistically. The PLGA/HAp/PGMs scaffold offers a novel option for sequential or simultaneous release of several drugs in terms of bone regeneration. PMID:22095448
Tang, Gongwen; Zhang, Hong; Zhao, Yunhui; Li, Xiao; Yuan, Xiaoyan; Wang, Min
The development of a scaffold able to mimic the mechanical properties of elastic tissues and to induce local angiogenesis by controlled release of angiogenic growth factors could be applied in the treatment of several ischemic diseases. For this purpose a composite scaffold made of a poly(ether)urethane-polydimethylsiloxane (PEtU-PDMS) semi-interpenetrating polymeric network (semi-IPN) and fibrin loaded growth factors (GFs), such as VEGF and bFGF, was manufactured using spray, phase-inversion technique. To evaluate the contribution of each scaffold component with respect to tissue response and in particular to blood vessel formation, three different scaffold formulations were developed as follows: 1) bare PEtU-PDMS; 2) PEtU-PDMS/Fibrin; and 3) PEtU-PDMS/Fibrin + GFs. Scaffolds were characterized in vitro respect to their morphology, VEGF and bFGF release kinetics and bioactivity. The induction of in vivo angiogenesis after subcutaneous and ischemic hind limb scaffold implantation in adult Wistar rats was evaluated at 7 and 14 days by immunohistological analysis (IHA), while Laser Doppler Perfusion Imaging (LDPI) was performed in the hind limbs at 0, 3, 7, 10 and 14 days. IHA of subcutaneously implanted samples showed that at 7 and 14 days the PEtU-PDMS/Fibrin + GFs scaffold induced a statistically significant increase in number of capillaries compared to bare PEtU-PDMS scaffold. IHA of ischemic hind limb showed that at 14 days the capillary number induced by PEtU-PDMS/Fibrin + GFs scaffolds was higher than that of PEtU-PDMS/Fibrin scaffolds. Moreover, at both time-points PEtU-PDMS/Fibrin scaffolds induced a significant increase in number of capillaries compared to bare PEtU-PDMS scaffolds. LDPI showed that at 10 and 14 days the ischemic/non-ischemic blood perfusion ratio was significantly greater in the PEtU-PDMS/Fibrin + GFs than in the other scaffolds. In conclusion, this study showed that the semi-IPN composite scaffold acting as a pro-angiogenic GFs delivery system has therapeutic potential for the local treatment of ischemic tissue and wound healing. PMID:20381861
Losi, Paola; Briganti, Enrica; Magera, Angela; Spiller, Dario; Ristori, Chiara; Battolla, Barbara; Balderi, Michela; Kull, Silvia; Balbarini, Alberto; Di Stefano, Rossella; Soldani, Giorgio
Nano/microfibrous polymeric constructs present various inherent advantages, such as highly porous architecture and high surface to volume ratio, making them attractive for tissue engineering purposes. Electrospinning is the most preferred technique for the fabrication of polymeric nanofibrous assemblies that can mimic the physical functions of native extracellular matrix greatly favoring cells attachment and thus influencing their morphology and activities. Different approaches have been developed to apply polymeric microfiber fabrication techniques (e.g. wet-spinning) for the obtainment of scaffolds with a three-dimensional network of micropores suitable for effective cells migration. Progress in additive manufacturing technology has led to the development of complex scaffold's shapes and microfibrous structures with a high degree of automation, good accuracy and reproducibility. Various loading methods, such as direct blending, coaxial electrospinning and microparticles incorporation, are enabling to develop customized strategies for the biofunctionalization of nano/microfibrous scaffolds with a tailored kinetics of release of different bioactive agents, ranging from small molecules, such as antibiotics, to protein drugs, such as growth factors, and even cells. Recent activities on the combination of different processing techniques and loading methods for the obtainment of biofunctionalized polymeric constructs with a complex multiscale structure open new possibilities for the development of biomimetic scaffolds endowed with a hierarchical architecture and a sophisticated release kinetics of different bioactive agents. This review is aimed at summarizing current advances in technologies and methods for manufacturing nano/microfibrous polymeric constructs suitable as tissue engineering scaffolds, and for their combination with different bioactive agents to promote tissue regeneration and therapeutic effects. PMID:24678016
Puppi, Dario; Zhang, Xuanmiao; Yang, Likai; Chiellini, Federica; Sun, Xun; Chiellini, Emo
Electrospinning is a promising technology for the fabrication of scaffolds in cartilage tissue engineering. Two other important elements for tissue engineering are seed cells and bioactive factors. Bone marrow-derived stem cells (BMSCs) and rhTGF-?1 are extensively studied for cartilage regeneration. However, little is known about scaffolds that can both specifically enrich BMSCs and release rhTGF-?1 to promote chondrogenic differentiation of the incorporated BMSCs. In this study, we first fabricated coaxial electrospun fibers using a polyvinyl pyrrolidone/bovine serum albumin/rhTGF-?1 composite solution as the core fluid and poly(?-caprolactone) solution as the sheath fluid. Structural analysis revealed that scaffold fibers were relatively uniform with a diameter of 674.4 ▒ 159.6 nm; the core-shell structure of coaxial fibers was homogeneous and proteins were evenly distributed in the core. Subsequently, the BMSC-specific affinity peptide E7 was conjugated to the coaxial electrospun fibers to develop a co-delivery system of rhTGF-?1 and E7. The results of (1)H nuclear magnetic resonance indicate that the conjugation between the E7 and scaffolds was covalent. The rhTGF-?1 incorporated in E7-modified scaffolds could maintain sustained release and bioactivity. Cell adhesion, spreading, and DNA content analyses indicate that the E7 promoted BMSC initial adhesion, and that the scaffolds containing both E7 and rhTGF-?1 (CBrhTE) were the most favorable for BMSC survival. Meanwhile, CBrhTE scaffolds could promote the chondrogenic differentiation ability of BMSCs. Overall, the CBrhTE scaffold could synchronously improve all three of the basic components required for cartilage tissue engineering in vitro, which paves the road for designing and building more efficient tissue scaffolds for cartilage repair. PMID:24703715
Man, Zhentao; Yin, Ling; Shao, Zhenxing; Zhang, Xin; Hu, Xiaoqing; Zhu, Jingxian; Dai, Linghui; Huang, Hongjie; Yuan, Lan; Zhou, Chunyan; Chen, Haifeng; Ao, Yingfang
The exclusive ability of acoustic waves to probe the structural, mechanical and fluidic properties of foams may offer novel approaches to characterise the porous scaffolds employed in tissue engineering. Motivated by this we conduct a preliminary investigation into the acoustic properties of a typical biopolymer and the feasibility of acoustic propagation within a foam scaffold thereof. Focussing on poly(lactic-co-glycolic acid), we use a pulse-echo method to determine the longitudinal speed of sound, whose temperature-dependence reveals the glass transition of the polymer. Finally, we demonstrate the first topographic and tomographic acoustic images of polymer foam tissue scaffolds.
N. G. Parker; M. L. Mather; S. P. Morgan; M. J. W. Povey
The exclusive ability of acoustic waves to probe the structural, mechanical and fluidic properties of foams may offer novel approaches to characterise the porous scaffolds employed in tissue engineering. Motivated by this we conduct a preliminary investigation into the acoustic properties of a typical biopolymer and the feasibility of acoustic propagation within a foam scaffold thereof. Focussing on poly(lactic-co-glycolic acid), we use a pulse-echo method to determine the longitudinal speed of sound, whose temperature-dependence reveals the glass transition of the polymer. Finally, we demonstrate the first topographic and tomographic acoustic images of polymer foam tissue scaffolds.
Parker, N G; Morgan, S P; Povey, M J W
Timely vascularization is essential for optimal performance of bone regenerative constructs. Vascularization is efficiently stimulated by vascular endothelial growth factor (VEGF), a substance with a short half-life time. This study investigates the controlled release of VEGF from gelatin microparticles (GMPs) as a means to prolong VEGF activity at the preferred location within 3D bioprinted scaffolds, and the effects on subsequent vascularization. The release of VEGF from GMPs was continuous for 3 weeks during in vitro studies, and bioactivity was confirmed using human endothelial progenitor cells (EPCs) in migration assays. Traditional and real-time migration assays showed immediate and efficient EPC migration in the presence of GMP-released VEGF, indistinguishable from VEGF-solution that was added to the medium. Matrigel scaffolds containing EPCs and VEGF, which was released either in a fast or sustained fashion by application of GMPs, were investigated for their in vivo vasculogenic capacity. Implantation in subcutaneous pockets in nude mice for one week demonstrated that vessel formation was significantly higher in the VEGF sustained-release group compared to the fast release group. In addition, regional differences with respect to VEGF release were introduced in 3D bioprinted EPC-laden scaffolds and their influence on vasculogenesis was investigated in vivo. The different regions were retained and vessel formation occurred analogous with the results seen in the Matrigel plugs. We conclude that GMPs are suitable to generate sustained release profiles of bioactive VEGF, and that they can be used to create defined differentiation regions in 3D bioprinted heterogeneous constructs, allowing a new generation of smart scaffold design. The prolonged presence of VEGF led to a significant increase in scaffold vascularization when applied in vivo. PMID:24727077
Poldervaart, Michelle T; Gremmels, Hendrik; van Deventer, Kelly; Fledderus, Joost O; Oner, F Cumhur; Verhaar, Marianne C; Dhert, Wouter J A; Alblas, Jacqueline
Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage.
The ability to develop tissue constructs with matrix composition and biomechanical properties that promote rapid tissue repair or regeneration remains an enduring challenge in musculoskeletal engineering. Current approaches require extensive cell manipulation ex vivo, using exogenous growth factors to drive tissue-specific differentiation, matrix accumulation, and mechanical properties, thus limiting their potential clinical utility. The ability to induce and maintain differentiation of stem cells in situ could bypass these steps and enhance the success of engineering approaches for tissue regeneration. The goal of this study was to generate a self-contained bioactive scaffold capable of mediating stem cell differentiation and formation of a cartilaginous extracellular matrix (ECM) using a lentivirus-based method. We first showed that poly-L-lysine could immobilize lentivirus to poly(?-caprolactone) films and facilitate human mesenchymal stem cell (hMSC) transduction. We then demonstrated that scaffold-mediated gene delivery of transforming growth factor ?3 (TGF-?3), using a 3D woven poly(?-caprolactone) scaffold, induced robust cartilaginous ECM formation by hMSCs. Chondrogenesis induced by scaffold-mediated gene delivery was as effective as traditional differentiation protocols involving medium supplementation with TGF-?3, as assessed by gene expression, biochemical, and biomechanical analyses. Using lentiviral vectors immobilized on a biomechanically functional scaffold, we have developed a system to achieve sustained transgene expression and ECM formation by hMSCs. This method opens new avenues in the development of bioactive implants that circumvent the need for ex vivo tissue generation by enabling the long-term goal of in situ tissue engineering. PMID:24550481
Brunger, Jonathan M; Huynh, Nguyen P T; Guenther, Caitlin M; Perez-Pinera, Pablo; Moutos, Franklin T; Sanchez-Adams, Johannah; Gersbach, Charles A; Guilak, Farshid
[Nutrigenomics--bioactive dietary components].
Nutrigenomics analyzes relations between diet and genes, and identifies mechanisms in which food and nutrition affect health and lifestyles and noncommunicable diseases (R. Chadwick, 2004). Bioactive dietary components are signal molecules that carry information from the external environment and affect in terms of quantity and quality in the process of gene expression. The biological effect of bioactive dietary components depends on various of physiological processes that can occur within a few genes. Polymorphism of genes can change their function and physiological response of the body for nutrients. Bioactive dietary components work on at least two levels of the expression of genes as factors regulating chromatin structure and as factors directly regulate the activity of nuclear receptors. The processes of synthesis and DNA repair are regulated by some of vitamins, macro-and micro-elements. They provide, among others, cofactors of enzymes that catalyze the replication of DNA methylation and its repair. DNA methylation profile may change under the influence of diet, single nucleotide polymorphisms and environmental factors. Bioactive dietary components may directly affect the process of gene expression by acting as ligands for nuclear receptors. Sensitive to dietary group of nuclear receptors are sensory receptors. This group includes, among others receptor PPAR (peroxisome proliferator activated), responsible for energy metabolism and receptors LXR (liver X receptor), FXR (farnesoid X receptor) and RXR, which is responsible for the metabolism of cholesterol. PMID:23619224
G?tek, Monika; Czech, Natalia; Fizia, Katarzyna; Bia?ek-Dratwa, Agnieszka; Muc-Wierzgo?, Ma?gorzata; Kokot, Teresa; Nowakowska-Zajdel, Ewa
Spirulina is produced from pure cultures of the photosynthetic prokaryotic cyanobacteria Arthrospira. For many years research centers throughout the world have studied its application in various scientific fields, especially in foods and medicine. The biomass produced from Spirulina cultivation contains a variety of biocompounds, including biopeptides, biopolymers, carbohydrates, essential fatty acids, minerals, oligoelements, and sterols. Some of these compounds are bioactive and have anti-inflammatory, antibacterial, antioxidant, and antifungal properties. These compounds can be used in tissue engineering, the interdisciplinary field that combines techniques from cell science, engineering, and materials science and which has grown in importance over the past few decades. Spirulina biomass can be used to produce polyhydroxyalkanoates (PHAs), biopolymers that can substitute synthetic polymers in the construction of engineered extracellular matrices (scaffolds) for use in tissue cultures or bioactive molecule construction. This review describes the development of nanostructured scaffolds based on biopolymers extracted from microalgae and biomass from Spirulina production. These scaffolds have the potential to encourage cell growth while reducing the risk of organ or tissue rejection. PMID:25157367
de Morais, Michele Greque; Vaz, Bruna da Silva; de Morais, Etiele Greque; Costa, Jorge Alberto Vieira
Spirulina is produced from pure cultures of the photosynthetic prokaryotic cyanobacteria Arthrospira. For many years research centers throughout the world have studied its application in various scientific fields, especially in foods and medicine. The biomass produced from Spirulina cultivation contains a variety of biocompounds, including biopeptides, biopolymers, carbohydrates, essential fatty acids, minerals, oligoelements, and sterols. Some of these compounds are bioactive and have anti-inflammatory, antibacterial, antioxidant, and antifungal properties. These compounds can be used in tissue engineering, the interdisciplinary field that combines techniques from cell science, engineering, and materials science and which has grown in importance over the past few decades. Spirulina biomass can be used to produce polyhydroxyalkanoates (PHAs), biopolymers that can substitute synthetic polymers in the construction of engineered extracellular matrices (scaffolds) for use in tissue cultures or bioactive molecule construction. This review describes the development of nanostructured scaffolds based on biopolymers extracted from microalgae and biomass from Spirulina production. These scaffolds have the potential to encourage cell growth while reducing the risk of organ or tissue rejection. PMID:25157367
de Morais, Michele Greque; Vaz, Bruna da Silva; de Morais, Etiele Greque; Costa, Jorge Alberto Vieira
PLGA Microspheres Incorporated Gelatin Scaffold: Microspheres Modulate Scaffold Properties
Freeze drying is one of the popular methods of fabrication for poly(lactide-co-glycolide) (PLGA) microspheres incorporated polymer scaffolds. However, the consequence of microspheres incorporation on physical and biological properties of scaffold has not been studied yet. In this study, attempt has been made to characterize the effect of PLGA microsphere incorporation on the physical properties of freeze-dried gelatin scaffold and its influence on cytocompatibility. Scaffolds loaded with varying amount of PLGA microspheres (10%, 1%, 0.1% w/w) were subjected to microarchitecture analysis, swelling, porosity, mechanical properties, biodegradation, cell adhesion, and cell proliferation studies. Results revealed that an increase in percentage loading of microspheres reduced the pore size and uniformity of the pore structure. Moreover, loading of PLGA microspheres up to 1% w/w significantly increased porosity, swelling, and mechanical properties of the scaffold but variations were not proportional for 10% w/w loading. Results also showed that PLGA microspheres have no significant effect on cell adhesion but influenced the growth kinetics. PMID:20126575
Banerjee, Indranil; Mishra, Debasish; Maiti, Tapas K.
We present the new fixation method for RHA (resurfacing hip arthroplasty) endoprostheses by means of the biomimetic multispiked connecting scaffold (MSC-Scaffold). Such connecting scaffold can generate new type of RHA endoprostheses, that is stemless and fixed entirely without cement. The preprototypes of this MSC-Scaffold were manufactured with modern additive laser additive technology (SLM). The pilot surgical implantations in animal model (two laboratory swine) of MSC-Scaffold preprototypes have showed after two months neither implant loosening, migration, and nor other early complications. From the results of performed histopathological evaluation of the periscaffold spikes bone tissue and 10-day culture of human osteoblasts (NHOst) we can conclude that (1) the scaffolding effect was obtained and (2) to improve the osseointegration of the scaffold spikes, their material surface should be physicochemically modified (e.g., with hydroxyapatite). Some histopathological findings in the periscaffold domain near the MSC-Scaffold spikes bases (fibrous connective tissue and metallic particles near the MSC-Scaffold spikes bases edges) prompt considering the necessity to optimize the design of the MSC-Scaffold in the regions of its interspike space near the spikes bases edges, to provide more room for new bone formation in this region and for indispensable post-processing (glass pearl blasting) after the SLM manufacturing. PMID:23984397
Uklejewski, Ryszard; Rogala, Piotr; Winiecki, Mariusz; Kedzia, Andrzej; Ruszkowski, Piotr
We present the new fixation method for RHA (resurfacing hip arthroplasty) endoprostheses by means of the biomimetic multispiked connecting scaffold (MSC-Scaffold). Such connecting scaffold can generate new type of RHA endoprostheses, that is stemless and fixed entirely without cement. The preprototypes of this MSC-Scaffold were manufactured with modern additive laser additive technology (SLM). The pilot surgical implantations in animal model (two laboratory swine) of MSC-Scaffold preprototypes have showed after two months neither implant loosening, migration, and nor other early complications. From the results of performed histopathological evaluation of the periscaffold spikes bone tissue and 10-day culture of human osteoblasts (NHOst) we can conclude that (1) the scaffolding effect was obtained and (2) to improve the osseointegration of the scaffold spikes, their material surface should be physicochemically modified (e.g., with hydroxyapatite). Some histopathological findings in the periscaffold domain near the MSC-Scaffold spikes bases (fibrous connective tissue and metallic particles near the MSC-Scaffold spikes bases edges) prompt considering the necessity to optimize the design of the MSC-Scaffold in the regions of its interspike space near the spikes bases edges, to provide more room for new bone formation in this region and for indispensable post-processing (glass pearl blasting) after the SLM manufacturing. PMID:23984397
Uklejewski, Ryszard; Rogala, Piotr; Winiecki, Mariusz; K?dzia, Andrzej; Ruszkowski, Piotr
Laser microstructured biodegradable scaffolds.
The two-photon polymerization technique (2PP) uses non-linear absorption of femtosecond laser pulses to selectively polymerize photosensitive materials. 2PP has the ability to fabricate structures with a resolution from tens of micrometers down to hundreds of nanometers. Three-dimensional microstructuring by the 2PP technique provides many interesting possibilities for biomedical applications. This microstructuring technique is suitable with many biocompatible polymeric materials, such as polyethylene glycol, polylactic acid, polycaprolactone, gelatin, zirconium-based hybrids, and others. The process of fabrication does not require clean room conditions and does not use hazard chemicals or high temperatures. The most beneficial property of 2PP is that it is capable of producing especially complex three-dimensional (3-D) structures, including devices with overhangs, without using any supportive structure. The flexibility in controlling geometries and feature sizes and the possibility to fabricate structures without the addition of new material layers makes this technique particularly appealing for fabrication of 3-D scaffolds for tissue engineering. PMID:23729598
Koroleva, Anastasia; Kufelt, Olga; Schlie-Wolter, Sabrina; Hinze, Ulf; Chichkov, Boris
Tissue engineering requires an ideal scaffold that will aid in the regeneration of the damaged tissues both structurally and functionally. Conventionally, polymeric nanofibrous scaffolds have been extensively used due to their structural similarity to the native extracellular matrix. Thus far, top-down approaches like electrospinning and phase separation have been predominantly used for the nanofiber fabrication. Recently, self-assembling peptide nanofibers (SAPNF) have been identified as promising scaffolds for tissue engineering applications. Molecular self-assembly of peptides, which is a bottom-up approach has laid foundations for the development of such novel scaffolds. Designer self-assembling peptides provide functional support as well as bio-recognition due to the presence of bioactive motifs embedded in them. However, there are certain limitations to both electrospun and SAPNF scaffolds in terms of synthesis, cues presented to the biological system and applications. Design of composite, hybrid scaffolds by super-positioning possible cues may result in effective functional tissue regeneration at multiple levels. PMID:23544748
Nune, Manasa; Kumaraswamy, Priyadharshini; Krishnan, Uma Maheswari; Sethuraman, Swaminathan
Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, that is, REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive and drug-resistant human cancer cell lines. MD simulation study on the paclitaxel mimics 1 and 2 as well as REDOR-Taxol bound to the 1JFF tubulin structure was quite informative to evaluate the level of mimicking. The MD simulation study clearly distinguishes the 5-6-6 and 5-7-6 tricyclic scaffolds, and also shows substantial difference in the conformational stability of the tubulin-bound structures between 2 and REDOR-Taxol. The latter may account for the large difference in potency, and provides critical information for possible improvement in the future design of paclitaxel mimics. PMID:20800500
Sun, Liang; Veith, Jean M; Pera, Paula; Bernacki, Ralph J; Ojima, Iwao
Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, i.e., REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive and drug-resistant human cancer cell lines. MD simulation study on the paclitaxel mimics 1 and 2 as well as REDOR-Taxol bound to the 1JFF tubulin structure was quite informative to evaluate the level of mimicking. The MD simulation study clearly distinguishes the 5-6-6 and 5-7-6 tricyclic scaffolds, and also shows substantial difference in the conformational stability of the tubulin-bound structures between 2 and REDOR-Taxol. The latter may account for the large difference in potency, and provides critical information for possible improvement in the future design of paclitaxel mimics. PMID:20800500
Sun, Liang; Veith, Jean M.; Pera, Paula; Bernacki, Ralph J.; Ojima, Iwao
Solvent/non-solvent sintering creates porous polymeric microsphere scaffolds suitable for tissue engineering purposes with control over the resulting porosity, average pore diameter and mechanical properties. Five different biodegradable biocompatible polyphosphazenes exhibiting glass transition temperatures from ?8░C to 41oC and poly(lactide-co-glycolide), (PLAGA) a degradable polymer used in a number of biomedical settings, were examined to study the versatility of the process and benchmark the process to heat sintering. Parameters such as: solvent/non-solvent sintering solution composition and submersion time effect the sintering process. PLAGA microsphere scaffolds fabricated with solvent/non-solvent sintering exhibited an interconnected porosity and pore size of 31.9% and 179.1Ąm respectively which was analogous to that of conventional heat sintered PLAGA microsphere scaffolds. Biodegradable polyphosphazene microsphere scaffolds exhibited a maximum interconnected porosity of 37.6% and a maximum compressive modulus of 94.3MPa. Solvent/non-solvent sintering is an effective strategy for sintering polymeric microspheres, with a broad spectrum of glass transition temperatures, under ambient conditions making it an excellent fabrication route for developing tissue engineering scaffolds and drug delivery vehicles. PMID:18161819
Brown, Justin L.; Nair, Lakshmi S.; Laurencin, Cato T.
Biomechanical properties of engineered collagen scaffolds
An experiment was performed to determine the effect of crosslinking on the stiffness of collagen scaffolds. Engineered non-crosslinked and dehydrothermally crosslinked chondroitin-6-sulfate collagen scaffolds were hydrated ...
Bonebreak, Christina M. (Christina Michelle)
Viscoelastic characterization of collagen-GAG scaffolds
An experimental study was performed to determine whether or not collagen-GAG scaffolds exhibit linear viscoelastic behavior. Tension tests were performed on dry and hydrated engineered collagen-GAG scaffolds in order to ...
Wong, Matthew Q
By using 2-N,6-O-sulfated chitosan (26SCS) immobilized poly(lactide-co-glycolide) (PLGA) scaffolds, our system achieved controlled release and improved bioactivity of recombinant human bone morphology protein-2 (rhBMP-2). Initially aminolyzed by ethylenediamine, PLGA scaffolds surface was immobilized with 26SCS via electrostatic assembly. Upon the presence of 26SCS, the system displayed improved rhBMP-2 adsorption and prolonged release process in vitro due to the high affinity of rhBMP-2 with 26SCS. On the other hand, because of incorporation of 26SCS, the system appeared to be more hydrophilic and provided a better environment for cells attachment. Moreover, 26SCS enhanced the binding efficiency between rhBMP-2 and its receptors as well as alkaline phosphatase activity. Our study highlights 26SCS immobilized PLGA scaffolds may be excellent candidates for use in bone tissue engineering. PMID:25084565
Kong, Xiangjun; Wang, Jing; Cao, Lingyan; Yu, Yuanman; Liu, Changsheng
Bioglass(«)-based scaffolds for bone tissue engineering have been developed, which can also serve as carriers for drug delivery. For this, P(3HB) microspheres (PMSs) loaded with tetracycline were fabricated and immobilised on the scaffold surfaces by a modified slurry dipping technique. The sustained drug delivery ability in simulated body fluid was confirmed by using UV-Vis absorption spectroscopy measurements. The MTT assay using mouse fibroblast cells provided evidence that the tetracycline loaded microspheres produced in this study show limited cytotoxicity. The scaffolds developed in this work provide mechanical support, adequate 3D surface roughness, bioactivity and controlled drug delivery function, and are thus interesting candidates for bone tissue engineering applications. PMID:23892485
Meng, D; Francis, L; Thompson, I D; Mierke, C; Huebner, H; Amtmann, A; Roy, I; Boccaccini, A R
Bioactive nanocrystalline sol-gel hydroxyapatite coatings.
Sol-gel technology offers an alternative technique for producing bioactive surfaces for improved bone attachment. Previous work indicated that monophasic hydroxyapatite coatings were difficult to produce. In the present work hydroxyapatite was synthesized using the sol-gel technique with alkoxide precursors and the solution was allowed to age up to seven days prior to coating. It was found that, similar to the wet-chemical method of hydroxyapatite powder synthesis, an aging time is required to produce a pure hydroxyapatite phase. A methodology that has been successfully used to produce nanocrystalline hydroxyapatite thin film coatings via the sol-gel route on various substrates including alumina, Vycor glass, partially stabilized zirconia, Ti-6Al-4V alloy and single crystal MgO is described. Coatings produced on MgO substrates were characterized by X-ray diffraction and atomic force microscopy, while the analogous gels were examined with thermogravimetric and differential thermal analyses. The coatings were crack free and the surface was covered with small grains, of approximately 200 nm in size for samples fired to 1000 degrees C. Coating thickness varied between 70 and 1000 nm depending on the number of applied layers. PMID:15348113
Chai, C S; Ben-Nissan, B
Designing Online Scaffolds for Interactive Computer Simulation
ERIC Educational Resources Information Center
The purpose of this study was to examine the effectiveness of online scaffolds in computer simulation to facilitate students' science learning. We first introduced online scaffolds to assist and model students' science learning and to demonstrate how a system embedded with online scaffolds can be designed and implemented to help highģ
Chen, Ching-Huei; Wu, I-Chia; Jen, Fen-Lan
Osteoblast response to polymethyl methacrylate bioactive glass composite.
Polymethylmethacrylate (PMMA) has been used in many orthopedic and dental applications since the 1960s. Biocompatibility of newly developed surface porous fiber reinforced (SPFR) PMMA based composite has not been previously proven in cell culture environment. Analysis of rat bone marrow stromal cells grown on the different test materials showed only little difference in normalized cell activity or bone sialoprotein (BSP) production between the test materials, but the osteocalcin (OC) levels remained higher (P < 0.015-0.005) through out the test with SPFR-material when compared to tissue culture poly styrene (TCPS). The cells grown on SP-FRC material also showed highest calcium depletion from the culture medium (P < 0.026-0.001) when compared to all other test substrates. SEM images of the cultured samples confirmed that all the materials enabled cell spreading and growth on their surface, but the roughened surface remarkably enhanced this process of cell attachment, division and calcified nodule formation. This study shows that the SP-FRC composite material does not elicit harmful/toxic reactions in cell cultures more than neutral TCPS and can be considered biocompatible. The material possesses good capabilities to form new mineralized tissue onto its surface, and through that a possibility to bond directly to bone. Rough surface seems to enhance osteoblast proliferation and formation of mineralized extracellular matrix. PMID:20162330
Hautamõki, M; Meretoja, V V; Mattila, R H; Aho, A J; Vallittu, P K
Bioactivity of Lemon Balm Kombucha
There is inadequate published data referring to bioactivity of lemon balm tea and its Kombucha. The aim of this study, therefore,\\u000a was to investigate antimicrobial, antiproliferative, genotoxic, and antigenotoxic potential of lemon balm tea and its Kombucha\\u000a with consuming acidity. Antimicrobial activity was determined by agar-well diffusion method. Cell growth effects were determined\\u000a in HeLa, MCF7, and HT-29 human tumor
Dragana D. ?etojevi?-Simin; Aleksandra S. Veli?anski; Dragoljub D. Cvetkovi?; SiniÜa L. Markov; Jasminka Ä. Mr?anovi?; ViÜnja V. Bogdanovi?; Slavica V. Ŗolaji?
Flavanols: digestion, absorption and bioactivity
Flavanols, or flavan-3-ols, are a family of bioactive compounds present in cocoa, red wine, green tea, red grapes, berries\\u000a and apples. With a basic monomer unit of (?)-epicatechin or (+)-catechin, flavanols can be present in foods and beverages\\u000a as monomers or oligomers (procyanidins). Most, but not all, procyanidins are degraded into monomer or dimer units prior to\\u000a absorption. The bioavailability
Robert M. Hackman; John A. Polagruto; Qin Yan Zhu; Buxiang Sun; Hajime Fujii; Carl L. Keen
Bioactive naphthoquinones from Cordyceps unilateralis
Six bioactive naphthoquinone derivatives, erythrostominone, deoxyerythrostominone, 4-O-methyl erythrostominone, epierythrostominol, deoxyerythrostominol and 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa-1,3-dienyl)-1,4-naphthoquinone, were isolated from the insect pathogenic fungus Cordyceps unilateralis BCC1869. While the latter is synthetically known, both it and 4-O-methyl erythrostominone are products of fungus strain C. unilateralis BCC1869.
Prasat Kittakoop; Juntira Punya; Palangpon Kongsaeree; Yuwapin Lertwerawat; Amnuay Jintasirikul; Morakot Tanticharoen; Yodhathai Thebtaranonth
Inorganic-organic hydrogels with tunable chemical and physical properties were prepared from methacrylated star polydimethylsiloxane (PDMSstar-MA) and diacrylated poly(ethylene glycol) (PEG-DA) for use as tissue engineering scaffolds. Eighteen compositionally unique hydrogels were prepared by photo-crosslinking varying weight ratios of PEG-DA and PDMSstar-MA of different molecular weights (Mn): PEG-DA (Mn = 3.4k and 6k g/mol) and PDMSstar-MA (Mn = 1.8k, 5k and 7k g/mol). Introduction of PDMSstar-MA caused formation of discrete PDMS-enriched microparticles dispersed within the PEG matrix. The swelling ratio, mechanical properties in tension and compression, non-specific protein adhesion, controlled introduction of bioactivity and cytotoxicity of hydrogels were studied. This library of inorganic-organic hydrogels with tunable properties provides a useful platform to study the effect of scaffold properties on cell behavior. PMID:20146518
Hou, Yaping; Schoener, Cody A.; Regan, Katherine R.; Munoz-Pinto, Dany; Hahn, Mariah S.; Grunlan, Melissa A.
In this study, simvastatin (SIM) drug incorporated poly(D,L-lactic-co-glycolide) (PLGA)/biphasic calcium phosphate (BCP) composite material (SPB) was coated on the BCP/ZrO2 (SPB-BCP/ZrO2) scaffold to enhance the mechanical and bioactive properties of the BCP/ZrO2 scaffold for bone engineering applications. The composite coating was prepared by combining different ratios of PLGA and BCP (1:2, 1:1, 2:1). After completion of the coating process, the compressive strength of the scaffolds was shown to increase with an increase in PLGA concentration from 8.5?▒?0.52?MPa for the SPB1-BCP/ZrO2 (1:2) to 11?▒?0.65?MPa for SPB3-BCP/ZrO2 (2:1) scaffolds when PLGA concentration was increased. Furthermore, the increase of PLGA in the coating composition corresponds to a decrease in porosity, degradation rate and weight loss of the scaffolds after 4 weeks. SIM release study demonstrated sustained release of the drug for the three kinds of scaffolds with improved biocompatibility. The increase of PLGA concentration also resulted in a lower release rate of SIM. Thus, the lower release rate of SIM brought upon by the increase of PLGA concentration further enhanced the performance of the scaffold in vitro making it a promising approach in the field of bone tissue regeneration. PMID:23815378
Sadiasa, Alexander; Kim, Min Sung; Lee, Byong Taek
Adrenomedullin (ADM) is a bioactive regulatory peptide that affects migration and proliferation of diverse cell types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. This study investigated the effects of sustained release of ADM on the modulation activity of osteoblasts and vascular endothelial cells in vitro. Chitosan microspheres (CMs) were developed for ADM delivery. Poly(lactic-co-glycolic) acid and nano-hydroxyapatite were used to prepare scaffolds containing microspheres with ADM. The CMs showed rough surface morphology and high porosity, and they were well-distributed. The scaffolds exhibited relatively uniform pore sizes with interconnected pores. The addition of CMs improved the mechanical properties of the scaffolds without affecting their high porosity. In vitro degradation tests indicated that the addition of CMs increased the water absorption of the scaffolds and inhibited pH decline of phosphate-buffered saline medium. The expression levels of osteogenic-related and angiogenic-related genes were determined in MG63 cells and in human umbilical vein endothelial cells cultured on the scaffolds, respectively. The expression levels of osteogenic-related and angiogenic-related proteins were also detected by western blot analysis. Their expression levels in cells were improved on the ADM delivery scaffolds at a certain time point. The in vitro evaluation suggests that the microsphere-scaffold system is suitable as a model for bone tissue engineering. PMID:23841075
Li, Chunyan; Chen, Yingxin; Dong, Shujun; Chen, Xuesi; Zhou, Yanmin
Problem Solving, Scaffolding and Learning
ERIC Educational Resources Information Center
Helping students to construct robust understanding of physics concepts and develop good solving skills is a central goal in many physics classrooms. This thesis examine students' problem solving abilities from different perspectives and explores strategies to scaffold students' learning. In studies involving analogical problem solvingģ
Lin, Shih-Yin
Influence of thermal treatment on the "in vitro" bioactivity of wollastonite materials.
The aim of this work was to study the influence of the composition and thermal treatment of the in vitro bioactivity of wollastonite materials obtained by sol-gel method. For this purpose, gels in the system SiO(2)-CaO were obtained applying calcium nitrate and tetraethoxysilicate as precursors. The gels were heated to 700 ░C and then sintered up to 1400 ░C. The bioactivity of the gel-derived materials in simulated body fluid (SBF) was investigated and characterized. Additional changes in ionic concentration, using inductively couple plasma atomic emission spectroscopy (ICP-AES), were determined. The results showed that all materials obtained were bioactive and indicate that the absence of phosphorous in the material composition is not an essential requirement for the development of a Hydroxyapatite layer. The bioactivity was influenced by the thermal treatment, the different phases (glass-phase, wollastonite and pseudowollastonite) as well as the porous size. On the gel-derived materials the bioactivity decreased with the sintering temperature. PMID:21336850
de la Casa-Lillo, Miguel A; Velßsquez, Pablo; De Aza, Piedad N
PURPOSE Tissue engineering solutions focused on the temporomandibular joint (TMJ) have expanded in number and variety over the past decade to address the treatment of TMJ disorders. The existing literature on approaches for healing small defects in the TMJ condylar cartilage and subchondral bone, however, is sparse. The purpose of this study was thus to evaluate the performance of a novel gradient-based scaffolding approach to regenerate osteochondral defects in the rabbit mandibular condyle. MATERIALS AND METHODS Miniature bioactive plugs for regeneration of small mandibular condylar defects in New Zealand White rabbits were fabricated. The plugs were constructed from poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres with a gradient transition between cartilage-promoting and bone-promoting growth factors. RESULTS At six weeks of healing, results suggested that the implants provided support for the neo-synthesized tissue as evidenced by histology and 9.4T magnetic resonance imaging. CONCLUSION The inclusion of bioactive factors in a gradient-based scaffolding design is a promising new treatment strategy for focal defect repair in the TMJ. PMID:21470747
Dormer, Nathan H.; Busaidy, Kamal; Berkland, Cory J.; Detamore, Michael S.
Optimization of a biomimetic poly-(lactic acid) ligament scaffold
NASA Astrophysics Data System (ADS)
The anterior cruciate ligament (ACL) is the most commonly injured ligament of the knee, often requiring orthopedic reconstruction using autograft or allograph tissue, both with significant disadvantages. As a result, tissue engineering an ACL replacement graft has been heavily investigated. The present study attempts to replicate the morphology and mechanical properties of the ACL using a nanomatrix composite of highly-aligned poly(lactic acid) (PLA) fibers with various surface and biochemical modifications. Additionally, this study attempts to recreate the natural mineralization gradient found at the ACL enthesis onto the scaffold, capable of inducing a favorable cellular response in vitro. Unidirectional electrospinning was used to create nanofibers of PLA, followed by an induced degradation of the nanofibers via 0.25M NaOH hydrolysis. The effects of the unidirectional electrospinning as well as the effects of NaOH hydrolysis on fiber alignment, fiber diameter, surface morphology, crystallinity, in vitro swelling, immobilization of fibrin, and mechanical properties were investigated, resulting in a modified morphology correlating to the microstructure of native ligament tissue with similar mechanical properties. Furthering the development of the PLA nanomatrix composite, a bioinkjet printer was used to immobilize nanoparticulate hydroxyapatite (HANP) on the surface of the scaffold. A series of 300pL droplets of HANP bioink were printed over a gradient pattern mimetic of (and spatially corresponding to) the mineralization gradient found over the microanatomy at the ACL enthesis. Proliferation and differentiation response of human mesenchymal stem cells (hMSCs) in vitro was assessed on a variety of conditions and combinations of the PLA nanofiber scaffold surface modifications (inclusive and exclusive of HANP, fibrin, and various time dependent NaOH treatments). It was found that a combinatory effect of the HANP gradient with fibrin on 20 minute NaOH treated PLA nanofibers enhanced the osteogenic differentiation of hMSCs, with an observable morphological change spatially corresponding to the compositional changes of the printed HANP gradient. Using the bioactive scaffold designed in this study as a template and expanding on the methods utilized, future studies can incorporate specific growth factors and other organic/inorganic biomolecules to further develop the engineered PLA nanomatrix into a functional ligament-replacement graft.
Uehlin, Andrew F.
NASA Technical Reports Server (NTRS)
Several NASA technologies have played part in growth and cost containment of studio glass art, among them a foam type insulation developed to meet a need for lightweight material that would reduce flame spread in aircraft fire. Foam comes in several forms and is widely used by glass artists, chiefly as an insulator for the various types of ovens used in glass working. Another Spinoff is alumina crucibles to contain molten glass. Before alumina crucibles were used, glass tanks were made of firebrick which tended to erode under high temperatures and cause impurities; this not only improved quality but made the process more cost effective. One more NASA technology that found its way into glass art working is a material known as graphite board, a special form of graphite originally developed for rocket motor applications. This graphite is used to exact compound angles and creates molds for poured glass artworks of dramatic design.
Cryopreserved dentin matrix as a scaffold material for dentin-pulp tissue regeneration.
Cryopreservation has been identified as an efficient approach to preserve tissue engineered products for a long term. Our prior studies have suggested that the treated dentin matrix (TDM) could be an ideal bioactive scaffold for dental tissue regeneration. In this study, we hypothesize that the cryopreservation could effectively maintain the survival and viability of dentinogenesis-related proteins of TDM and the cryopreserved dentin matrix (CDM) would provide the suitable biological scaffold and inductive microenvironment for the regeneration of dentin-pulp like tissue. CDM-3 and CDM-6 were prepared by cryopreserving TDM in liquid nitrogen (-196Ā░C) with cryoprotectant for 3 months and 6 months, respectively. Various biological characteristics of CDM, including mechanical properties, cell proliferation, and odontogenesis ability, were investigated. To further evaluate the inductive capacity of CDM, human dental follicle cells were encapsulated within CDM, and implanted the scaffold into a mouse model for 8 weeks, and the grafts were harvested and assessed histologically. The CDM showed superior mechanical properties than TDM. Compared to TDM, CDM can release more dentinogenesis-related proteins due to the larger pore diameter. Cell proliferation with the addition of CDM extract liquid was similar to that of TDM in the first five days. Human dental follicle cells, under the effect of CDM extract liquid, highly expressed bone sialoprotein, collagen-1, alkaline phosphatase, indicating that CDM, regarded as the inductive microenvironment, plays an important role in odontogenesis. Most importantly, inĀvivo, CDM could induce dental follicle cells to regenerate new dentin-pulp like tissues, such as dentinal tubules, predentin, collagen fibers, nerves, and blood vessels which were positive for dentin sialophosphoprotein, dental matrix protein-1, Tubulin, and collagen-1. In conclusion, CDM is an ideal biological scaffold material for human dentin-pulp like tissue regeneration. These findings indicated that TDM could be preserved as the tissue engineering scaffold that is readily available for patient treatments. Furthermore, the success of cryopreservation of TDM may also provide an insight into preserving other bioactive scaffold materials of tissue engineering. PMID:24680189
Jiao, Liang; Xie, Li; Yang, Bo; Yu, Mei; Jiang, Zongting; Feng, Lian; Guo, Weihua; Tian, Weidong
Regenerative medicine approaches for the treatment of damaged or missing myocardial tissue include cell-based therapies, scaffold-based therapies, and/or the use of specific growth factors and cytokines. The present study evaluated the ability of extracellular matrix (ECM) derived from porcine urinary bladder to serve as an inductive scaffold for myocardial repair. ECM scaffolds have been shown to support constructive remodeling of other tissue types including the lower urinary tract, the dermis, the esophagus, and dura mater by mechanisms that include the recruitment of bone marrow-derived progenitor cells, angiogenesis, and the generation of bioactive molecules that result from degradation of the ECM. ECM derived from the urinary bladder matrix, identified as UBM, was configured as a single layer sheet and used as a biologic scaffold for a surgically created 2 cm2 full-thickness defect in the right ventricular free wall. Sixteen dogs were divided into two equal groups of eight each. The defect in one group was repaired with a UBM scaffold and the defect in the second group was repaired with a Dacron patch. Each group was divided into two equal subgroups (n = 4), one of which was sacrificed 15 min after surgical repair and the other of which was sacrificed after 8 weeks. Global right ventricular contractility was similar in all four subgroups groups at the time of sacrifice. However, 8 weeks after implantation the UBM-treated defect area showed significantly greater (p < 0.05) regional systolic contraction compared to the myocardial defects repaired with by Dacron (3.3 +/- 1.3% vs. -1.8 +/- 1.1%; respectively). Unlike the Dacron-repaired region, the UBM-repaired region showed an increase in systolic contraction over the 8-week implantation period (-4.2 +/- 1.7% at the time of implantation vs. 3.3 +/- 1.3% at 8 weeks). Histological analysis showed the expected fibrotic reaction surrounding the embedded Dacron material with no evidence for myocardial regeneration. Histologic examination of the UBM scaffold site showed cardiomyocytes accounting for approximately 30% of the remodeled tissue. The cardiomyocytes were arranged in an apparently randomly dispersed pattern throughout the entire tissue specimen and stained positive for alpha- sarcomeric actinin and Connexin 43. The thickness of the UBM graft site increased greatly from the time of implantation to the 8-week sacrifice time point when it was approximately the thickness of the normal right ventricular wall. Histologic examination suggested complete degradation of the originally implanted ECM scaffold and replacement by host tissues. We conclude that UBM facilitates a constructive remodeling of myocardial tissue when used as replacement scaffold for excisional defects. PMID:16826793
Badylak, Stephen F; Kochupura, Paul V; Cohen, Ira S; Doronin, Sergey V; Saltman, Adam E; Gilbert, Thomas W; Kelly, Damon J; Ignotz, Ronald A; Gaudette, Glenn R
While protein-surface interactions have been widely studied, relatively little is understood at this time regarding how protein-surface interaction effects are influenced by protein-protein interactions and how these effects combine with the internal stability of a protein to influence its adsorbed-state structure and bioactivity. The objectives of this study were to develop a method to study these combined effects under widely varying protein-protein interaction conditions using hen egg-white lysozyme (HEWL) adsorbed on silica glass, poly(methyl methacrylate), and polyethylene as our model systems. In order to vary protein-protein interaction effects over a wide range, HEWL was first adsorbed to each surface type under widely varying protein solution concentrations for 2h to saturate the surface, followed by immersion in pure buffer solution for 15h to equilibrate the adsorbed protein layers in the absence of additionally adsorbing protein. Periodic measurements were made at selected time points of the areal density of the adsorbed protein layer as an indicator of the level of protein-protein interaction effects within the layer, and these values were then correlated with measurements of the adsorbed protein's secondary structure and bioactivity. The results from these studies indicate that protein-protein interaction effects help stabilize the structure of HEWL adsorbed on silica glass, have little influence on the structural behavior of HEWL on HDPE, and actually serve to destabilize HEWL's structure on PMMA. The bioactivity of HEWL on silica glass and HDPE was found to decrease in direct proportion to the degree of adsorption-induce protein unfolding. A direct correlation between bioactivity and the conformational state of adsorbed HEWL was less apparent on PMMA, thus suggesting that other factors influenced HEWL's bioactivity on this surface, such as the accessibility of HEWL's bioactive site being blocked by neighboring proteins or the surface itself. The developed methods provide an effective means to characterize the influence of protein-protein interaction effects and provide new molecular-level insights into how protein-protein interaction effects combine with protein-surface interaction and internal protein stability effects to influence the structure and bioactivity of adsorbed protein. PMID:23751416
Wei, Yang; Thyparambil, Aby A; Latour, Robert A
While protein-surface interactions have been widely studied, relatively little is understood at this time regarding how protein-surface interaction effects are influenced by protein-protein interactions and how these effects combine with the internal stability of a protein to influence its adsorbed-state structure and bioactivity. The objectives of this study were to develop a method to study these combined effects under widely varying protein-protein interaction conditions using hen egg-white lysozyme (HEWL) adsorbed on silica glass, poly(methyl methacrylate), and polyethylene as our model systems. In order to vary protein-protein interaction effects over a wide range, HEWL was first adsorbed to each surface type under widely varying protein solution concentrations for 2 h to saturate the surface, followed by immersion in pure buffer solution for 15 h to equilibrate the adsorbed protein layers in the absence of additionally adsorbing protein. Periodic measurements were made at selected time points of the areal density of the adsorbed protein layer as an indicator of the level of protein-protein interaction effects within the layer, and these values were then correlated with measurements of the adsorbed proteinÆs secondary structure and bioactivity. The results from these studies indicate that protein-protein interaction effects help stabilize the structure of HEWL adsorbed on silica glass, have little influence on the structural behavior of HEWL on HDPE, and actually serve to destabilize HEWLÆs structure on PMMA. The bioactivity of HEWL on silica glass and HDPE was found to decrease in direct proportion to the degree of adsorption-induce protein unfolding. A direct correlation between bioactivity and the conformational state of adsorbed HEWL was less apparent on PMMA, thus suggesting that other factors influenced HEWLÆs bioactivity on this surface, such as the accessibility of HEWLÆs bioactive site being blocked by neighboring proteins or the surface itself. The developed methods provide an effective means to characterize the influence of protein-protein interaction effects and provide new molecular-level insights into how protein-protein interaction effects combine with protein-surface interaction and internal protein stability effects to influence the structure and bioactivity of adsorbed protein. PMID:23751416
Wei, Yang; Thyparambil, Aby A.; Latour, Robert A.
A biohybrid composite consisting of extracellular matrix (ECM) gel from porcine dermal tissue and biodegradable elastomeric fibers was generated and evaluated for soft tissue applications. ECM gel possesses attractive biocompatibility and bioactivity with weak mechanical properties and rapid degradation, while electrospun biodegradable poly(ester urethane)urea (PEUU) has good mechanical properties but limited cellular infiltration and tissue integration. A concurrent gel electrospray/polymer electrospinning method was employed to create ECM gel/PEUU fiber composites with attractive mechanical properties, including high flexibility and strength. Electron microscopy revealed a structure of interconnected fibrous layers embedded in ECM gel. Tensile mechanical properties could be tuned by altering the PEUU/ECM weight ratio. Scaffold tensile strengths for PEUU/ECM ratios of 67/33, 72/28 and 80/20 ranged from 80 to 187 kPa in the longitudinal axis (parallel to the collecting mandrel axis) and 41-91 kPa in the circumferential axis with 645-938% breaking strains. The 72/28 biohybrid composite and a control scaffold generated from electrospun PEUU alone were implanted into Lewis rats, replacing a full-thickness abdominal wall defect. At 4 wk, no infection or herniation was found at the implant site. Histological staining showed extensive cellular infiltration into the biohybrid scaffold with the newly developed tissue well integrated with the native periphery, while minimal cellular ingress into the electrospun PEUU scaffold was observed. Mechanical testing of explanted constructs showed evidence of substantial remodeling, with composite scaffolds adopting properties more comparable to the native abdominal wall. The described elastic biohybrid material imparts features of ECM gel bioactivity with PEUU strength and handling to provide a promising composite biomaterial for soft tissue repair and replacement. PMID:21303718
Hong, Yi; Huber, Alexander; Takanari, Keisuke; Amoroso, Nicholas J; Hashizume, Ryotaro; Badylak, Stephen F; Wagner, William R
Scaffolding Proteins in Cardiac Myocytes
Post-translational modification, such as protein phosphorylation, plays a critical role to reversibly amplify and modulate\\u000a signaling pathways. Since kinases and phosphatases have broad substrate recognition motifs, compartmentalization and localization\\u000a of signaling complexes are required to achieve specific signals. Scaffolds are proteins that associate with two or more binding\\u000a partners and function to enhance the efficiency and\\/or specificity of cellular signaling
N. L. Chudasama; S. O. Marx; S. F. Steinberg
Scaffold Design for Bone Regeneration
The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues. PMID:24730250
Polo-Corrales, Liliana; Latorre-Esteves, Magda; Ramirez-Vick, Jaime E.
Hydrogels and scaffolds for immunomodulation.
For over two decades, immunologists and biomaterials scientists have co-existed in parallel world with the rationale of understanding the molecular profile of immune responses to vaccination, implantation, and treating incurable diseases. Much of the field of biomaterial-based immunotherapy has relied on evaluating model antigens such as chicken egg ovalbumin in mouse models but their relevance to humans has been point of much discussion. Nevertheless, such model antigens have provided important insights into the mechanisms of immune regulation and served as a proof-of-concept for plethora of biomaterial-based vaccines. After years of extensive development of numerous biomaterials for immunomodulation, it is only recently that an experimental scaffold vaccine implanted beneath the skin has begun to use the human model to study the immune responses to cancer vaccination by co-delivering patient-derived tumor lysates and immunomodulatory proteins. If successful, this scaffold vaccine will change the way we approached untreatable cancers, but more importantly, will allow a faster and more rational translation of therapeutic regimes to other cancers, chronic infections, and autoimmune diseases. Most materials reviews have focused on immunomodulatory adjuvants and micro-nano-particles. Here we provide an insight into emerging hydrogel and scaffold based immunomodulatory approaches that continue to demonstrate efficacy against immune associated diseases. PMID:25155610
Singh, Ankur; Peppas, Nicholas A
Partially biodegradable porous scaffolds incorporating bioactive molecules prepared by clean techniques posses an enormous interest in tissue engineering applications. Poly(methyl methacrylate)¢poly(l-lactic acid) (PMMA¢PLA) blends were submitted to CO2 supercritical conditions (P=160¢260bar, T=60░C) after certain time and then rapidly depressurized to obtain porous structures that have been related with the supercritical parameters and to the polymer blend composition. In some cases
D. Velasco; L. Benito; M. Fernßndez-Gutiķrrez; J. San Romßn; C. Elvira
Electrospun linear polyethyleneimine scaffolds for cell growth
Unique biocompatible scaffolds were produced by electrospinning cross-linked linear polyethyleneimine (PEI) with succinic anhydride and 1,4-butanediol diglycidyl ether. Nonwoven mats of PEI fibers in the range of 1600¢687nm were evaluated as interaction scaffolds for normal human fibroblast (NHF) cells. The electrospun scaffolds were characterized by Fourier transform infrared spectroscopy and ultraviolet¢visible spectroscopy. The growth of the NHF cells was followed
Nadia Khanam; Carole Mikoryak; Rockford K. Draper; Kenneth J. Balkus
What Do Scaffold Proteins Really Do?
NSDL National Science Digital Library
Scaffold proteins play an important role in coordinating signal transduction cascades. However, their exact mechanism of action and the ultimate effect they have on the signal output remain unclear. Ferrell discusses how computer simulations have provided insight into the multiple possible functions that scaffold proteins may have. What remains is to test the predictions in real cells to determine what difference the presence of a scaffold really makes in the output of a signaling pathway.
James E. Ferrell (Stanford University School of Medicine;Department of Molecular Pharmacology REV)
We report on the rational design and synthesis of a new type of bioactive poly(ethylene glycol) diacrylate (PEGDA) macromers, cyclic Arg-Gly-Asp (cRGD)-PEGDA, to mimic the cell-adhesive properties of extracellular matrix (ECM), aiming to create biomimetic scaffolds with controlled spatial organization of ligands and enhanced cell binding affinity for tissue engineering. To attach the cRGD peptide in the middle of PEGDA chain, a tailed cRGD peptide, c[RGDfE(SSSKK-NH2)] (1) was synthesized with c(RGDfE) linked to a tail of SSSKK. The tail consists of a spacer with three serine residues, and a linker with two lysine residues for conjugating with acryloyl-PEG-NHS (5) to create cRGD-PEGDA (6). cRGD-PEGDA possesses good ability of photopolymerization to fabricate hydrogel scaffolds under UV radiation. Surface morphology and composition analysis demonstrates that cRGD-PEGDA hydrogels were well-constructed with porous three-dimensional (3D) structures and uniform distribution of cRGD ligands. Our results show that cRGD-PEGDA hydrogels facilitate endothelial cell (EC) adhesion and spreading on the hydrogel surfaces, and exhibit significantly higher EC population in comparison with linear RGD-modified hydrogels at low peptide incorporation. Since ligand presentation in biomimetc scaffolds plays an important role in controlling cell behaviors, cRGD-PEGDA has great advantages of controlling hydrogel properties and ligand spatial organization in the resulting scaffolds. Furthermore, cRGD-PEGDA is an attractive candidate for the future development of tissue engineering scaffolds with optimum cell adhesive strength and ligand density. PMID:19191566
Zhu, Junmin; Tang, Chad; Kottke-Marchant, Kandice; Marchant, Roger E.
Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine
Polymer hydrogels have been widely explored as therapeutic delivery matrices because of their ability to present sustained, localized and controlled release of bioactive factors. Bioactive factor delivery from injectable biopolymer hydrogels provides a versatile approach to treat a wide variety of diseases, to direct cell function and to enhance tissue regeneration. The innovative development and modification of both natural-(e.g., alginate (ALG), chitosan, hyaluronic acid (HA), gelatin, heparin (HEP), etc.) and synthetic-(e.g., polyesters, polyethyleneimine (PEI), etc.) based polymers has resulted in a variety of approaches to design drug delivery hydrogel systems from which loaded therapeutics are released. This review presents the state-of-the-art in a wide range of hydrogels that are formed though self-assembly of polymers and peptides, chemical crosslinking, ionic crosslinking and biomolecule recognition. Hydrogel design for bioactive factor delivery is the focus of the first section. The second section then thoroughly discusses release strategies of payloads from hydrogels for therapeutic medicine, such as physical incorporation, covalent tethering, affinity interactions, on demand release and/or use of hybrid polymer scaffolds, with an emphasis on the last 5 years.
Nguyen, Minh Khanh; Alsberg, Eben
Multilayered electrospun scaffolds for tendon tissue engineering.
Full-thickness rotator cuff tears are one of the most common causes of shoulder pain in people over the age of 65. High retear rates and poor functional outcomes are common after surgical repair, and currently available extracellular matrix scaffold patches have limited abilities to enhance new tendon formation. In this regard, tissue-engineered scaffolds may provide a means to improve repair of rotator cuff tears. Electrospinning provides a versatile method for creating nanofibrous scaffolds with controlled architectures, but several challenges remain in its application to tissue engineering, such as cell infiltration through the full thickness of the scaffold as well as control of cell growth and differentiation. Previous studies have shown that ligament-derived extracellular matrix may enhance differentiation toward a tendon or ligament phenotype by human adipose stem cells (hASCs). In this study, we investigated the use of tendon-derived extracellular matrix (TDM)-coated electrospun multilayered scaffolds compared to fibronectin (FN) or phosphate-buffered saline (PBS) coating for use in rotator cuff tendon tissue engineering. Multilayered poly(?-caprolactone) scaffolds were prepared by sequentially collecting electrospun layers onto the surface of a grounded saline solution into a single scaffold. Scaffolds were then coated with TDM, FN, or PBS and seeded with hASCs. Scaffolds were maintained without exogenous growth factors for 28 days in culture and evaluated for protein content (by immunofluorescence and biochemical assay), markers of tendon differentiation, and tensile mechanical properties. The collagen content was greatest by day 28 in TDM-scaffolds. Gene expression of type I collagen, decorin, and tenascin C increased over time, with no effect of scaffold coating. Sulfated glycosaminoglycan and dsDNA contents increased over time in culture, but there was no effect of scaffold coating. The Young's modulus did not change over time, but yield strain increased with time in culture. Histology demonstrated cell infiltration through the full thickness of all scaffolds and immunofluorescence demonstrated greater expression of type I, but not type III collagen through the full thickness of the scaffold in TDM-scaffolds compared to other treatment groups. Together, these data suggest that nonaligned multilayered electrospun scaffolds permit tenogenic differentiation by hASCs and that TDM may promote some aspects of this differentiation. PMID:23808760
Chainani, Abby; Hippensteel, Kirk J; Kishan, Alysha; Garrigues, N William; Ruch, David S; Guilak, Farshid; Little, Dianne
Multilayered Electrospun Scaffolds for Tendon Tissue Engineering
Full-thickness rotator cuff tears are one of the most common causes of shoulder pain in people over the age of 65. High retear rates and poor functional outcomes are common after surgical repair, and currently available extracellular matrix scaffold patches have limited abilities to enhance new tendon formation. In this regard, tissue-engineered scaffolds may provide a means to improve repair of rotator cuff tears. Electrospinning provides a versatile method for creating nanofibrous scaffolds with controlled architectures, but several challenges remain in its application to tissue engineering, such as cell infiltration through the full thickness of the scaffold as well as control of cell growth and differentiation. Previous studies have shown that ligament-derived extracellular matrix may enhance differentiation toward a tendon or ligament phenotype by human adipose stem cells (hASCs). In this study, we investigated the use of tendon-derived extracellular matrix (TDM)-coated electrospun multilayered scaffolds compared to fibronectin (FN) or phosphate-buffered saline (PBS) coating for use in rotator cuff tendon tissue engineering. Multilayered poly(?-caprolactone) scaffolds were prepared by sequentially collecting electrospun layers onto the surface of a grounded saline solution into a single scaffold. Scaffolds were then coated with TDM, FN, or PBS and seeded with hASCs. Scaffolds were maintained without exogenous growth factors for 28 days in culture and evaluated for protein content (by immunofluorescence and biochemical assay), markers of tendon differentiation, and tensile mechanical properties. The collagen content was greatest by day 28 in TDM-scaffolds. Gene expression of type I collagen, decorin, and tenascin C increased over time, with no effect of scaffold coating. Sulfated glycosaminoglycan and dsDNA contents increased over time in culture, but there was no effect of scaffold coating. The Young's modulus did not change over time, but yield strain increased with time in culture. Histology demonstrated cell infiltration through the full thickness of all scaffolds and immunofluorescence demonstrated greater expression of type I, but not type III collagen through the full thickness of the scaffold in TDM-scaffolds compared to other treatment groups. Together, these data suggest that nonaligned multilayered electrospun scaffolds permit tenogenic differentiation by hASCs and that TDM may promote some aspects of this differentiation. PMID:23808760
Chainani, Abby; Hippensteel, Kirk J.; Kishan, Alysha; Garrigues, N. William; Ruch, David S.; Guilak, Farshid
To exploit the therapeutic potential of growth factors in tissue regeneration, it is necessary to design a porous scaffold in order to concurrently accommodate cells and release angiogenic factors in a controlled manner. In an attempt to address these issues, we developed a nanocomposite scaffold based on silk/calcium phosphate/PLGA by freeze-drying and electrospinning in order to control the release of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). The highly porous scaffold possessed appropriate chemical and physical structure as confirmed by FTIR, XRD, SEM, and Zeta potential analysis. Furthermore, the incorporation of PDGF and VEGF in the scaffold was confirmed using Raman spectroscopy while their bioactivity was maintained by 82% and 89% for up to 28 days, respectively. The release of PDGF was slower than VEGF as respected. Additionally, the scaffold could promote proliferation, alkaline phosphatase production and attachment of human osteoblast cells. Histological examination established new bone matrix formation with neovascularization in the angiogenic factors loaded scaffold after 10 weeks of implantation in rabbit model. Finally, it was considered that the fabricated nanocomposite could be useful for bone tissue engineering applications. PMID:23856159
Farokhi, Mehdi; Mottaghitalab, Fatemeh; Ai, Jafar; Shokrgozar, Mohammad Ali
NASA Astrophysics Data System (ADS)
In this work, protein adsorption and cell adhesion on three-dimensional (3D) polycaprolactone (PCL) scaffolds treated by plasma etching and deposition were performed. The 3D PCL scaffold used as a substrate of a bone tissue was fabricated by recent rapid prototype techniques. To increase surface properties, such as hydrophilicity, roughness, and surface chemistry, through good protein adhesion on scaffolds, oxygen (O2) plasma etching and acrylic acid or allyamine plasma deposition were performed on the 3D PCL scaffolds. The O2 plasma etching induced the formation of random nanoporous structures on the roughened surfaces of the 3D PCL scaffolds. The plasma deposition with acrylic acid and allyamine induced the chemical modification for introducing a functional group. The protein adsorption increased on the O2 plasma-etched surface compared with an untreated 3D PCL scaffold. MC3T3-E1 cells adhered bioactively on the etched and deposited surface compared with the untreated surface. The present plasma modification might be sought as an effective technique for enhancing protein adsorption and cell adhesion.
Myung, Sung Woon; Ko, Yeong Mu; Kim, Byung Hoon
Bioactive constituents of Conyza albida.
The bioactivity-guided fractionation of an active chloroform extract of Conyza albida led to the isolation of three alkenynes, deca-4,6-diyn-2-(Z)-enoic methyl ester (1), deca-4,6-diyn-2-(Z)-enoic ethyl ester (2) and deca-2,4-diene-4-hydroxy-6-yn-1,4-olide (3), and the terpenoid spathulenol (4), as the active toxic metabolites in the Artemia sp. lethality test. When tested in the KB cell cytotoxicity assay, compounds 1-4 demonstrated IC50 values of 52.2, 38.4, 117.9, and 83.8 microM, respectively. All compounds studied were inactive in the DNA methyl green and DNA strand scission assays, while compounds 3 and 4 showed moderate activity as inhibitors of human topoisomerase I. Compound 2 is reported here for the first time. PMID:11199128
Pacciaroni, A V; Mongelli, E; Ariza Espinar, L; Romano, A; Ciccia, G; Silva, G L
Angiogenic effects of borate glass microfibers in a rodent model.
The primary objective of this research was to evaluate the use of bioactive borate-based glass microfibers for angiogenesis in soft tissue repair applications. The effect of these fibers on growth of capillaries and small blood vessels was compared to that of 45S5 silica glass microfibers and sham implant controls. Compressed mats of three types of glass microfibers were implanted subcutaneously in rats and tissues surrounding the implant sites histologically evaluated 2-4 weeks post surgery. Bioactive borate glass 13-93B3 supplemented with 0.4 wt % copper promoted extensive angiogenesis as compared to silica glass microfibers and sham control tissues. The angiogenic responses suggest the copper-containing 13-93B3 microfibers may be effective for treating chronic soft tissue wounds. A second objective was to assess the possible systemic cytotoxicity of dissolved borate ions and other materials released from implanted borate glass microfibers. Cytotoxicity was assessed via histological evaluation of kidney tissue collected from animals 4 weeks after subcutaneously implanting high amounts of the borate glass microfibers. The evaluation of the kidney tissue from these animals showed no evidence of chronic histopathological changes in the kidney. The overall results indicate the borate 2glass microfibers are safe and effective for soft tissue applications. ® 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4491-4499, 2014. PMID:24677635
Lin, Yinan; Brown, Roger F; Jung, Steven B; Day, Delbert E
NSDL National Science Digital Library
In this activity, learners explore why frost forms. They create their own frost using a solution of ice water and salt in a glass. The salt allows the temperature of the water to drop below the normal freezing point, so that water vapor in the air turns directly into solid ice on the surface of the glass.
This paper surveys the present state of knowledge concerning the production, stability and structure of metallic glasses made by rapid quenching from the melt, and outlines their principal magnetic, electrical and mechanical properties. Emphasis is placed on the influence of annealing, at temperatures below the glass transition, on a range of properties. The prospect for practical applications is examined, with
R. W. Cahn
Nano-fibrous scaffolds for tissue engineering
With the ability to form nano-fibrous structures, a drive to mimic the extracellular matrix (ECM) and form scaffolds that are an artificial extracellular matrix suitable for tissue formation has begun. These nano-fibrous scaffolds attempt to mimic collagen, a natural extracellular matrix component, and could potentially provide a better environment for tissue formation in tissue engineering systems. Three different approaches toward
L. A. Smith; P. X. Ma
Scaffolds in tissue engineering bone and cartilage
Musculoskeletal tissue, bone and cartilage are under extensive investigation in tissue engineering research. A number of biodegradable and bioresorbable materials, as well as scaffold designs, have been experimentally and\\/or clinically studied. Ideally, a scaffold should have the following characteristics: (i) three-dimensional and highly porous with an interconnected pore network for cell growth and flow transport of nutrients and metabolic waste;
Dietmar W. Hutmacher
Biomimetic Collagen Scaffolds with Anisotropic Pore Architecture
. The manipulation of the structure of collagen scaffolds using a freeze-drying technique was explored in this work as an intrinsically biocompatible way of tailoring the inner architecture of the scaffold. The research was focused on the influence of temperature...
Davidenko, Natalia; Gibb, T; Schuster, Carlos; Best, Serena Michelle; Campbell, JJ; Watson, CJ; Cameron, Ruth Elizabeth
Melt electrospinning of biodegradable polyurethane scaffolds
Electrospinning from a melt, in contrast to from a solution, is an attractive tissue engineering scaffold manufacturing process as it allows for the formation of small diameter fibers while eliminating potentially cytotoxic solvents. Despite this, there is a dearth of literature on scaffold formation via melt electrospinning. This is likely due to the technical challenges related to the need for
Ari Karchin; Felix I. Simonovsky; Buddy D. Ratner; Joan E. Sanders
Biomimetic hollow scaffolds for long bone replacement
The tissue engineering focuses on synthesis or regeneration of tissues and organs. The hierarchical structure of nearly all porous scaffolds on the macro, micro- and nanometer scales resembles that of engineering foams dedicated for technical applications, but differ from the complex architecture of long bone. A major obstacle of scaffold architecture in tissue regeneration is the limited cell infiltration as
Bert M³ller; Hans Deyhle; Fabienne C. Fierz; Stephan H. Irsen; Jin Y. Yoon; Shpend Mushkolaj; Oliver Boss; Elke Vorndran; Uwe Gburek; ųzer Degistirici; Michael Thie; Barbara Leukers; Felix Beckmann; Frank Witte
A Conceptualisation of Whole-Class Scaffolding
ERIC Educational Resources Information Center
The concept of scaffolding refers to temporary and adaptive support, originally in dyadic adult-child interaction. It has become widely used, also in whole-class settings, but often in loose ways. The aim of this paper is to theoretically and empirically ground a conceptualisation of whole-class scaffolding so that it remains close to the originģ
Smit, Jantien; van Eerde, Henriļtte A. A.; Bakker, Arthur
Architecture of metaphase chromosomes and chromosome scaffolds
We have developed procedures for depositing intact mitotic chromosomes and isolated residual scaffolds on electron microscope grids at controlled and reproducible levels of compaction. The chromosomes were isolated using a recently developed aqueous method. Our study has addressed two different aspects of chromosome structure. First, we present a method for improved visualization of radial chromatin loops in undisrupted mitotic chromosomes. Second, we have visualized a nonhistone protein residual scaffold isolated from nuclease-digested chromosomes under conditions of low salt protein extraction. These scaffolds, which have an extremely simple protein composition, are the size of chromosomes, are fibrous in nature, and are found to retain differentiated regions that appear to derive from the kinetochores and the chromatid axis. When our standard preparation conditions were used, the scaffold appearance was found to be very reproducible. If the ionic conditions were varied, however, the scaffold appearance underwent dramatic changes. In the presence of millimolar concentrations of Mg++ or high concentrations of NaCl, the fibrous scaffold protein network was observed to undergo a lateral aggregation or assembly into a coarse meshlike structure. The alteration of scaffold structure was apparently reversible. This observation is consistent with a model in which the scaffolding network plays a dynamic role in chromosome condensation at mitosis. PMID:6826654
Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that plays a critical role during bone regeneration and repair. In the extracellular environment, sulfated polysaccharides anchored covalently to glycoproteins such as syndecan and also non-covalently to fibronectin fibers have been shown to bind BMP-2 through a heparin-binding domain and regulate its bioactivity. We report here on a synthetic biomimetic strategy that emulates biological BMP-2 signaling through the use of peptide amphiphile nanofibers designed to bind heparin. The supramolecular nanofibers, which integrate the biological role of syndecan and fibronectin, were allowed to form gel networks within the pores of an absorbable collagen scaffold by simply infiltrating dilute solutions of the peptide amphiphile, heparan sulfate, and BMP-2. The hybrid biomaterial enhanced significantly bone regeneration in a rat critical-size femoral defect model using BMP-2 amounts that are one order of magnitude lower than required for healing in this animal model. Using micro-computed tomography, we also showed that the hybrid scaffold was more effective at bridging within the gap relative to a conventional scaffold of the type used clinically based on collagen and BMP-2. Histological evaluation also revealed the presence of more mature bone in the new ossified tissue when the low dose of BMP-2 was delivered using the biomimetic supramolecular system. These results demonstrate how molecularly designed materials that mimic features of the extracellular environment can amplify the regenerative capacity of growth factors. PMID:23099062
Lee, Sungsoo S.; Huang, Brian J.; Kaltz, Stuart R.; Sur, Shantanu; Newcomb, Christina J.; Stock, Stuart R.; Shah, Ramille N.; Stupp, Samuel I.
Advances in the design of macroporous polymer scaffolds for potential applications in dentistry
A paradigm shift is taking place in medicine and dentistry from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous three-dimensional (3D) material hydrogels integrated with cells and bioactive factors to regenerate tissues such as dental bone and other oral tissues. Hydrogels have been established as a biomaterial of choice for many years, as they offer diverse properties that make them ideal in regenerative medicine, including dental applications. Being highly biocompatible and similar to native extracellular matrix, hydrogels have emerged as ideal candidates in the design of 3D scaffolds for tissue regeneration and drug delivery applications. However, precise control over hydrogel properties, such as porosity, pore size, and pore interconnectivity, remains a challenge. Traditional techniques for creating conventional crosslinked polymers have demonstrated limited success in the formation of hydrogels with large pore size, thus limiting cellular infiltration, tissue ingrowth, vascularization, and matrix mineralization (in the case of bone) of tissue-engineered constructs. Emerging technologies have demonstrated the ability to control microarchitectural features in hydrogels such as the creation of large pore size, porosity, and pore interconnectivity, thus allowing the creation of engineered hydrogel scaffolds with a structure and function closely mimicking native tissues. In this review, we explore the various technologies available for the preparation of macroporous scaffolds and their potential applications. PMID:24455437
Braschler, Thomas M.; Renaud, Philippe
ECM inspired coating of embroidered 3D scaffolds enhances calvaria bone regeneration.
Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13?mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767
Rentsch, C; Rentsch, B; Heinemann, S; Bernhardt, R; Bischoff, B; F÷rster, Y; Scharnweber, D; Rammelt, S
The Effect of Source Animal Age Upon Extracellular Matrix Scaffold Properties
Biologic scaffold materials composed of mammalian extracellular matrix (ECM) are commonly used for the repair and reconstruction of injured tissues. An important, but unexplored variable of biologic scaffolds is the age of the animal from which the ECM is prepared. The objective of the present study was to compare the structural, mechanical, and compositional properties of small intestinal submucosa (SIS)-ECM harvested from pigs that differed only in age. Degradation product bioactivity of these ECM materials was also examined. Results showed that there are distinct differences in each of these variables among the various age source ECM scaffolds. The strength and growth factors content of ECM from 3 week old animals is less than that of ECM harvested from 12, 26 or >52 week old animals. The elastic modulus of SIS-ECM for 3 week and >52 week old source was less than that of the 12 and 26 week source. Degradation products from all age source ECMs were chemotactic for perivascular stem cells, with the 12 week source the most potent, while the oldest source caused the greatest increase in proliferation. In summary, distinct differences exist in the mechanical, structural, and biologic properties of SIS-ECM harvested from different aged animals. PMID:20870285
Tottey, S.; Johnson, S. A.; Crapo, P. M.; Reing, J. E.; Zhang, L.; Jiang, H.; Medberry, C. J.; Reines, B.; Badylak, S.F.
Nanomaterials are rich in potential, particularly for the formation of scaffolds that mimic the landscape of the host environment of the cell. This niche arises from the spatial organization of a series of biochemical and biomechanical signals. Self-assembling peptides have emerged as an important tool in the development of functional (bio-)nanomaterials; these simple, easily synthesized subunits form structures which present the properties of these larger, more complex systems. Scaffolds based upon these nanofibrous matrices are promising materials for regenerative medicine as part of a new methodology in scaffold design where a "bottom-up" approach is used in order to simulate the native cellular milieu. Importantly, SAPs hold the potential to be bioactive through the presentation of biochemical and biomechanical signals in a context similar to the natural extracellular matrix, making them ideal targets for providing structural and chemical support in a cellular context. Here, we discuss a new methodology for the presentation of biologically relevant epitopes through their effective presentation on the surface of the nanofibers. Here, we demonstrate that these signals have a direct effect on the viability of cells within a three-dimensional matrix as compared with an unfunctionalized, yet mechanically and morphologically similar system. ® 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 197-205, 2014. PMID:24488709
Modepalli, Vengama N; Rodriguez, Alexandra L; Li, Rui; Pavuluri, Sivapriya; Nicholas, Kevin R; Barrow, Colin J; Nisbet, David R; Williams, Richard J
ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration
Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13?mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767
Rentsch, C.; Rentsch, B.; Heinemann, S.; Bernhardt, R.; Bischoff, B.; Forster, Y.; Scharnweber, D.; Rammelt, S.
Encapsulation for preservation of functionality and targeted delivery of bioactive food components
There has been a tremendous increase in the number of food products containing bioactive components with a health promoting or disease preventing effect. Bioactive food components can be divided into bioactive molecules and bioactive living cells (probiotics). Both bioactive molecules and bioactive living cells may benefit from encapsulation since many report low survival of bioactivity due to adverse effects of
Paul de Vos; Marijke M. Faas; Milica Spasojevic; Jan Sikkema
Methods are surveyed for recycling and\\/or reusing post-consumer glass products to determine which methods are most favorable. The following topics are included: the properties of glass, glass manufacture; analyses of alternatives to direct disposal of glass products; reuse of waste glass for glass manufacture; techniques for the separation of glass from municipal refuse; the development of degradable glass containers; returnable
H. R. Samtur
To improve the bioactivity and degradation behavior of biodegradable magnesium, biodegradable metal matrix composites with the ZK30 magnesium alloy as the matrix and bioactive glass (BG, 45S5) as the reinforcement were prepared. The microstructures of the ZK30-BG composites showed homogeneous dispersion of BG particles throughout the matrix. XRD and EDX analyses confirmed the retention of the morphological characteristics and composition of BG particles in the composites. Immersion tests in the minimum essential medium with Earle's balanced salts at 37░C showed that the composites with 5 and 10% BG had lower rates of degradation and hydrogen evolution than the matrix alloy. In addition, the tests confirmed that the composites possessed an enhanced ability to induce calcium and phosphate ion deposition on sample surfaces during degradation, suggesting accelerated surface mineralization that would lead to improved bioactivity when compared with the matrix alloy. In vitro cytotoxicity tests showed that the ionic products of the composites formed during degradation possessed a superior ability to support the survival, proliferation, and osteoblastic differentiation of bone marrow stromal cells to those of the ZK30 alloy. The ZK30-BG composites with enhanced bioactivity and reduced degradation rate could be promising biodegradable materials for orthopedic implants. ® 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 437-446, 2012. PMID:22121143
Huan, Zhiguang; Leeflang, Sander; Zhou, Jie; Zhai, Wanyin; Chang, Jiang; Duszczyk, Jurek
Nerve regeneration after spinal cord injuries (SCI) remains suboptimal despite recent advances in the field. One major hurdle is the rapid clearance of drugs from the injury site, which greatly limits therapeutic outcomes. Nanofiber scaffolds represent a potential class of materials for enhancing nerve regeneration because of its biomimicking architecture. In this study, we investigated the feasibility of incorporating neurotrophin-3 (NT-3) and chondroitinase ABC (ChABC) onto electrospun collagen nanofibers for SCI treatment. By using microbial transglutaminase (mTG) mediated crosslinking, proteins were loaded onto electrospun collagen nanofibers at an efficiency of ?45-48%. By combining NT-3 with heparin during the protein incorporation process, a sustained release of NT-3 was obtained (?96% by day 28). As indicated by dorsal root ganglion outgrowth assay, NT-3 incorporated collagen scaffolds supported neuronal culture and neurite outgrowth for a longer time period than bolus delivery of NT-3. The presence of heparin also protected ChABC from degradation. Specifically, as evaluated by dimethylmethylene blue assay, bioactive ChABC was detected from collagen scaffolds for at least 32 days in vitro in the presence of heparin (?32% of bioactivity retained). In contrast, ChABC bioactivity was only ?1.9% by day 22 in the absence of heparin. Taken together, these results clearly demonstrated the feasibility of incorporating NT-3 and ChABC via mTG immobilization to produce protein-incorporated collagen nanofibers. Such biofunctional nanofiber constructs may find useful applications in SCI treatment by providing topographical signals and multiple biochemical cues that can promote nerve regeneration while antagonizing axonal growth inhibition for CNS regeneration. PMID:22042649
Liu, Ting; Xu, Jinye; Chan, Barbara P; Chew, Sing Yian
Proton transfer in organic scaffolds
NASA Astrophysics Data System (ADS)
This dissertation focuses on the fundamental understanding of the proton transfer process and translating the knowledge into design/development of new organic materials for efficient non-aqueous proton transport. For example, what controls the shuttling of a proton between two basic sites? a) Distance between two groups? or b) the basicity? c) What is the impact of protonation on molecular conformation when the basic sites are attached to rigid scaffolds? For this purpose, we developed several tunable proton sponges and studied proton transfer in these scaffolds theoretically as well as experimentally. Next we moved our attention to understand long-range proton conduction or proton transport. We introduced liquid crystalline (LC) proton conductor based on triphenylene molecule and established that activation energy barrier for proton transport is lower in the LC phase compared to the crystalline phase. Furthermore, we investigated the impact of several critical factors: the choice of the proton transferring groups, mobility of the charge carriers, intrinsic vs. extrinsic charge carrier concentrations and the molecular architectures on long-range proton transport. The outcome of this research will lead to a deeper understanding of non-aqueous proton transfer process and aid the design of next generation proton exchange membrane (PEM) for fuel cell.
Basak, Dipankar
The Use of Fetal Bovine Dermal Scaffold (PriMatrix) in the Management of Full-Thickness Hand Burns
Objective: Management of full-thickness burn wounds represents a challenge when reconstructive options are not applicable. Fetal bovine dermal matrix is a bioactive collagen scaffold that assimilates into wounds and stimulates vascularization and dermal regeneration. Methods: We present the use of fetal bovine dermal scaffold PriMatrix in the treatment of a patient who sustained scald-immersion full-thickness burns of her bilateral hands that failed conventional wound therapy. Results: A 71-year-old woman with advanced Parkinson's disease sustained self-induced 5% mixed second- and third-degree scald-immersion burns of her bilateral hands and fingers. The patient underwent extensive debridement that resulted in partially avascular wounds measuring 66 cm2 and 72 cm2 with exposed extensor tendons and no evidence of bleeding. Meshed homograft was applied, but her hands remained partly avascular. PriMatrix fetal bovine dermal scaffold was applied to provide tissue remodeling over the bones, which allowed successful skin grafting and complete wound healing. Conclusions: Our experience shows fetal bovine dermal scaffold to be an effective method in management of complicated burn wounds in selected cases. Further studies need to be implemented to confer this conclusion. PMID:25328569
Karcich, Jenika; Granick, Mark S.; Marano, Michael A.
Trabecular scaffolds created using micro CT guided fused deposition modeling
Free form fabrication and high resolution imaging techniques enable the creation of biomimetic tissue engineering scaffolds. A 3D CAD model of canine trabecular bone was produced via micro CT and exported to a fused deposition modeler, to produce polybutylene terephthalate (PBT) trabeculated scaffolds and four other scaffold groups of varying pore structures. The five scaffold groups were divided into subgroups
B. C. Tellis; J. A. Szivek; C. L. Bliss; D. S. Margolis; R. K. Vaidyanathan; P. Calvert
Low temperature sintering of fluorapatite glass-ceramics.
Fluorapatite glass-ceramics have been shown to be excellent candidates as scaffold materials for bone grafts, however, scaffold production by sintering is hindered by concurrent crystallization of the glass. Objective, our goal was to investigate the effect of Ca/Al ratio on the sintering behavior of Nb-doped fluorapatite-based glasses in the SiO2-Al2O3-P2O5-MgO-Na2O-K2O-CaO-CaF2 system. Methods, glass compositions with Ca/Al ratio of 1 (A), 2 (B), 4 (C) and 19 (D) were prepared by twice melting at 1525░C for 3h. Glasses were either cast as cylindrical ingots or ground into powders. Disk-shaped specimens were prepared by either sectioning from the ingots or powder-compacting in a mold, followed by heat treatment at temperatures ranging between 700 and 1050░C for 1h. The density was measured on both sintered specimens and heat treated discs as controls. The degree of sintering was determined from these measurements. Results and Significance XRD showed that fluorapatite crystallized in all glass-ceramics. A high degree of sintering was achieved at 775░C for glass-ceramic D (98.99▒0.04%), and 900░C for glass-ceramic C (91.31▒0.10). Glass-ceramics A or B were only partially sintered at 1000░C (63.6▒0.8% and 74.1▒1.5%, respectively). SEM revealed a unique microstructure of micron-sized spherulitic fluorapatite crystals in glass-ceramics C and D. Increasing the Ca/Al ratio promoted low temperature sintering of fluorapatite glass-ceramics, which are traditionally difficult to sinter. PMID:24252652
Denry, Isabelle; Holloway, Julie A
NSDL National Science Digital Library
In this activity, learners discover the principles of edible glass by making a supersaturated sugar solution. The goal of this activity is to provide an interesting experiment which learners of many different levels can perform. The write-up for this activity provides explanatory information that presents the experiment from several different perspectives. This activity includes an introduction to common sugars, as well as some discussion of temperature and thermometry, basic thermodynamics, and the experimental procedure to make the candy glass.
Pomeroy, Josh
Surface Characterization of Extracellular Matrix Scaffolds
Extracellular matrix (ECM) scaffolds prepared from different tissue sources or using different methods have been demonstrated to have distinctive effects upon cell adhesion patterns and the ability to support and maintain differentiated phenotypes. It is unknown whether the molecular composition or the ultrastructure of the ECM plays a greater role in determining the phenotype of the cells with which it comes into contact. However, when implanted, the topology and ligand landscape of the material will determine the host molecules that bind and the type and behavior of cells that mediate the host response. Therefore, a comprehensive understanding of surface characteristics is essential in the design of scaffolds for specific clinical applications. The surface characteristics of ECM scaffolds derived from porcine urinary bladder, small intestine, and liver as well as the effects of two commonly used methods of chemical cross-linking upon UBM were investigated. Electron microscopy and time of flight secondary ion mass spectroscopy were used to examine the surface characteristics of the scaffolds. The results show that ECM scaffolds have unique morphologic and structural properties which are dependant on the organ or tissue from which the scaffold is harvested. Furthermore, the results show that the surface characteristics of an ECM scaffold are changed through chemical cross-linking. PMID:19828192
Brown, Bryan N.; Barnes, Christopher A.; Kasick, Rena T.; Michel, Roger; Gilbert, Thomas W.; Beer-Stolz, Donna; Castner, David G.; Ratner, Buddy D.; Badylak, Stephen F.
Surface characterization of extracellular matrix scaffolds.
Extracellular matrix (ECM) scaffolds prepared from different tissue sources or using different methods have been demonstrated to have distinctive effects upon cell adhesion patterns and the ability to support and maintain differentiated phenotypes. It is unknown whether the molecular composition or the ultrastructure of the ECM plays a greater role in determining the phenotype of the cells with which it comes into contact. However, when implanted, the topology and ligand landscape of the material will determine the host molecules that bind and the type and behavior of cells that mediate the host response. Therefore, a comprehensive understanding of surface characteristics is essential in the design of scaffolds for specific clinical applications. The surface characteristics of ECM scaffolds derived from porcine urinary bladder, small intestine, and liver as well as the effects of two commonly used methods of chemical cross-linking upon UBM were investigated. Electron microscopy and time of flight secondary ion mass spectroscopy were used to examine the surface characteristics of the scaffolds. The results show that ECM scaffolds have unique morphologic and structural properties which are dependant on the organ or tissue from which the scaffold is harvested. Furthermore, the results show that the surface characteristics of an ECM scaffold are changed through chemical cross-linking. PMID:19828192
Brown, Bryan N; Barnes, Christopher A; Kasick, Rena T; Michel, Roger; Gilbert, Thomas W; Beer-Stolz, Donna; Castner, David G; Ratner, Buddy D; Badylak, Stephen F
Scaffold Translation: Barriers Between Concept and Clinic
Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges. PMID:21902613
Murphy, William L.
Biomimetic nanofibrous scaffolds for bone tissue engineering
Bone tissue engineering is a highly interdisciplinary field that seeks to tackle the most challenging bone-related clinical issues. The major components of bone tissue engineering are the scaffold, cells, and growth factors. This review will focus on the scaffold and recent advancements in developing scaffolds that can mimic the natural extracellular matrix of bone. Specifically, these novel scaffolds mirror the nanofibrous collagen network that comprises the majority of the non-mineral portion of bone matrix. Using two main fabrication techniques, electrospinning and thermally-induced phase separation, and incorporating bone-like minerals, such as hydroxyapatite, composite nanofibrous scaffolds can improve cell adhesion, stem cell differentiation, and tissue formation. This review will cover the two main processing techniques and how they are being applied to fabricate scaffolds for bone tissue engineering. It will then cover how these scaffolds can enhance the osteogenic capabilities of a variety of cell types and survey the ability of the constructs to support the growth of clinically relevant bone tissue. PMID:21944829
Holzwarth, Jeremy M.; Ma, Peter X.
ILP-based maximum likelihood genome scaffolding
Background Interest in de novo genome assembly has been renewed in the past decade due to rapid advances in high-throughput sequencing (HTS) technologies which generate relatively short reads resulting in highly fragmented assemblies consisting of contigs. Additional long-range linkage information is typically used to orient, order, and link contigs into larger structures referred to as scaffolds. Due to library preparation artifacts and erroneous mapping of reads originating from repeats, scaffolding remains a challenging problem. In this paper, we provide a scalable scaffolding algorithm (SILP2) employing a maximum likelihood model capturing read mapping uncertainty and/or non-uniformity of contig coverage which is solved using integer linear programming. A Non-Serial Dynamic Programming (NSDP) paradigm is applied to render our algorithm useful in the processing of larger mammalian genomes. To compare scaffolding tools, we employ novel quantitative metrics in addition to the extant metrics in the field. We have also expanded the set of experiments to include scaffolding of low-complexity metagenomic samples. Results SILP2 achieves better scalability throughg a more efficient NSDP algorithm than previous release of SILP. The results show that SILP2 compares favorably to previous methods OPERA and MIP in both scalability and accuracy for scaffolding single genomes of up to human size, and significantly outperforms them on scaffolding low-complexity metagenomic samples. Conclusions Equipped with NSDP, SILP2 is able to scaffold large mammalian genomes, resulting in the longest and most accurate scaffolds. The ILP formulation for the maximum likelihood model is shown to be flexible enough to handle metagenomic samples. PMID:25253180
Improved bioactivity of PAN-based carbon nanofibers decorated with bioglass nanoparticles.
Composite nanofibers composed of polyacrylonitrile (PAN)-based carbon nanofibers and bioactive glass (BG) nanoparticles have been prepared by electrospinning and in situ sintering. Morphology observation showed that the BG nanoparticles of size 20-50?nm were uniformly distributed on the surface of composite nanofibers with 350?nm average diameter after carbonization. Biological mineralization indicated the formation of apatite-like layer on the surface of composite nanofibers, in which the composition of carbonate hydroxyapatite was proved by FTIR and XRD analysis. Cell growth dynamics according to cellular morphology, CCK-8 assay, and alkaline phosphatase activity assay exhibited better cell adhesion, proliferation, and osteogenic induction of bone marrow-derived mesenchymal stem cells cultured on the composite nanofibers, which suggested the higher bioactivity of composite nanofibers compared to pure PAN-based carbon nanofibers. PMID:24266838
Han, Bing; Zhang, Xuehui; Liu, Haiyang; Deng, Xuliang; Cai, Qing; Jia, Xiaolong; Yang, Xiaoping; Wei, Yan; Li, Gang
The effect of micro-gravity and bioactive surfaces on the mineralization of bone
NASA Astrophysics Data System (ADS)
The loss of bone density with age especially for women, is one of the most serious health complications affecting humans An increased incidence of fractured hips and long bones, and collapse of vertebrae are all due to loss of bone density. Demineralization of bone also poses one of the most severe limitations on long-duration manned space flight. This study investigates the hypothesis that chemical effects responsible for enhanced osteoblast differentiation and proliferation observed in-vitro and in-vivo at 1-gravity with bioactive glasses may be sufficient to prevent the turn-off of bone cells that occurs in ?-g or other reduced loading environments as a consequence of age or immobility. To conduct this work, the authors developed an embryonic mouse long-bone model to examine the interaction of bioactive surfaces and ions with the influence of a simulated ?-g environment.
Maroothynaden, J.; Hench, J. J.
Electrospinning technology is an attractive process for the fabrication of a scaffold with an annulus fibrosus (AF)-like architecture for tissue engineering. Oriented and nonoriented electrospun scaffolds were prepared from poly(ester-urethane) (PU) and poly(?-caprolactone) (PCL) as well as corresponding homogeneous films. Scaffolds' characteristics and mechanical properties were characterized by scanning electron microscopy, static water contact measurements, and dynamic mechanical analysis, respectively. The effect of scaffold architecture and polymer composition on bovine AF cells was investigated. PU and PCL films and scaffolds supported AF cell growth and extracellular matrix production and accumulation. Electrospun scaffolds increased the retention of collagen and glycosaminoglycan compared with films. Fiber orientation of the scaffolds promoted the AF cell phenotype with a trend toward an upregulation of matrix gene expression for oriented relative to nonoriented scaffolds. The higher yield strain of an oriented electrospun PU scaffold, compared with other scaffolds, will be advantageous for AF tissue engineering under a dynamic mechanical environment. PMID:24131280
Wismer, Nadine; Grad, Sibylle; Fortunato, Giuseppino; Ferguson, Stephen J; Alini, Mauro; Eglin, David
The association of stem cells (SCs) with biomaterials promises to be the protagonist for future regenerative medicine in the treatment of tissue and organ lesions. Stem cells were cultivated in scaffolds constructed by the electrospinning technique, using poly-D,L-lactic acid (PDLLA) associated or not with Spirulina biomass (PDLLA/Sp), which has bioactive components of interest for tissue engineering (TE). Physicochemical analyses were performed, such as morphology, fiber diameter, degradability, residual solvent, roughness, contact angle with water, among others. SCs adhesion, proliferation and scaffold cytotoxicity were also evaluated. Nanofibers without beads and with characteristics similar to the natural extracellular matrix (ECM) in terms of mechanical and topographical properties were obtained. In biological tests it was found that SCs adhered more and had greater viability in the PDLLA/Sp molds, when compared with the PDLLA scaffolds. The scaffolds were shown to be atoxic for the SCs. It can be concluded that the scaffolds developed in this work have the characteristics to be a new biomaterial suitable for use in TE. PMID:23621033
Steffens, D; Lersch, M; Rosa, A; Scher, C; Crestani, T; Morais, M G; Costa, J A V; Pranke, P
A glass belonging to the system SiO(2)-Al(2)O(3)-CaO-Na(2)O has been subjected to a patented ion-exchange treatment to induce surface antibacterial activity by doping with silver ions. Doped samples have been characterized by means of X-Ray diffraction (XRD), scanning electron microscopy (SEM) observation, energy dispersion spectrometry (EDS) analysis, in vitro bioactivity test, Ag(+) leaching test by graphite furnace atomic absorption spectroscopy (GFAAS) analyses, cytotoxicity tests by fibroblasts adhesion and proliferation, adsorption of IgA and IgG on to the material to evaluate its inflammatory property and antibacterial tests (cultures with Staphylococcus aureus and Escherichia coli). In vitro tests results demonstrated that the modified glass maintains the same biocompatibility of the untreated one and, moreover, it acquires an antimicrobial action against tested bacteria. This method can be selected to realize glass or glass-ceramic bone substitutes as well as coatings on bio-inert devices, providing safety against bacterial colonization thus reducing the risks of infections nearby the implant site. The present work is the carrying on of a previous research activity, concerning the application of an ion-exchange treatment on glasses belonging to the ternary system SiO(2)-CaO-Na(2)O. On the basis of previous results the glass composition was refined and the ion-exchange process was adapted to it, in order to tune the final material properties. The addition of Al(2)O(3) to the original glass system and the optimization of the ion-exchange conditions allowed a better control of the treatment, leading to an antibacterial material, without affecting both bioactivity and biocompatibility. PMID:18987954
Vernķ, E; Miola, M; Vitale Brovarone, C; Cannas, M; Gatti, S; Fucale, G; Maina, G; Massķ, A; Di Nunzio, S
Domains, Motifs, and Scaffolds: The Role of
-4154/06/0707- 0655$20.00 Key Words signal transduction, modularity, evolvability, docking, synthetic biology Abstract . . . . . . . . . . . . . . . . . . . . . . 669 REWIRING SIGNALING PATHWAYS: SYNTHETIC BIOLOGY. . . . . . . . . . . . . . . . . . . . . . . 671 Synthetic Scaffolds, Adapters, and Docking Interactions . . . . . . . . . . 672 Synthetic Signaling Switches
Lim, Wendell
Organ engineering based on decellularized matrix scaffolds.
End-organ failure is one of the major healthcare challenges in the Western world. Yet, donor organ shortage and the need for immunosuppression limit the impact of transplantation. The regeneration of whole organs could theoretically overcome these hurdles. Early milestones have been met by combining stem and progenitor cells with increasingly complex scaffold materials and culture conditions. Because the native extracellular matrix (ECM) guides organ development, repair and physiologic regeneration, it provides a promising alternative to synthetic scaffolds and a foundation for regenerative efforts. Perfusion decellularization is a novel technology that generates native ECM scaffolds with intact 3D anatomical architecture and vasculature. This review summarizes achievements to date and discusses the role of native ECM scaffolds in organ regeneration. PMID:21514224
Song, Jeremy J; Ott, Harald C
Designing Appropriate Scaffolding for Student Science Projects
NSDL National Science Digital Library
The authors have developed a successful approach to teaching and inspiring undergraduate science and nonscience majors to complete creditable, semester-long, hands-on science research projects. This approach utilizes a carefully developed scaffolding consisting of in-class exercises and discussions, preparatory homework and lab events, and three well-calibrated milestones prior to submission of students' final report. This scaffolding has increased student confidence and the caliber of final projects.
Johnson, Marie; Smith, Mark
Next-generation orthopedic implants with both osteoinductivity and antibacterial ability are greatly needed. In the present study, biodegradable rhBMP-2 loaded zein-based scaffolds with a macroporous structure were synthesized, and SBA-15 nanoparticles and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) were incorporated into the scaffolds to produce an anti-infective composite scaffold for delivery of osteogenic factors that facilitate the functional repair of bone defects. The silica/HACC/zein scaffolds developed here showed bioactivity, biocompatibility, and effective antibacterial activity. Confocal laser scanning microscopy (CLSM) was used to quantitatively measure the bactericidal efficacy with respect to bacterial adhesion. Results showed that the sample zein-HACC-S20 exhibited long-lasting antibacterial activity against Escherichia coli and Staphylococcus aureus up to 5Ād. At a low dosage of rhBMP-2 (ca. 80Ā?g), the scaffolds released rhBMP-2 protein efficiently at a relatively slow rate, even after 27Ād. An ALP activity and ECM mineralization assay showed that the zein-HACC-S20 scaffolds exhibited significant early osteogenic differentiation by generating enhanced ALP product on day 14 and ECM mineralization on day 21. In a mouse model of thigh muscle pouches, zein-S20 and zein-HACC-S20 groups resulted in obvious bone formation and gave more extensive mineralization to the implants than silica free groups, indicating effective bone induction inĀvivo. In a rabbit model of critical-sized radius bone defects (20Āmm in length and 5Āmm in diameter), the bone defects were almost fully repaired and bone marrow cavity recanalization was detectable by 3D micro-CT technique and histological analysis after 12 weeks. In this way, the zein-HACC-S20 scaffolds were proven to significantly promote the bone repair. They also demonstrated considerable promise for tissue engineering. Silica/HACC/ze