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The present invention pertains to mineral fibers useful as biomimetics of tissue, such as dental enamel and bone, and as filler in paper, paint, coatings, and plastic production. The present invention also concerns methods for producing mineral fibers by contacting an inorganic liquid-phase mineral precursor with a crystalline inorganic substrate under conditions permitting the inorganic liquid-phase mineral precursor to solidify and crystallize, compositions comprising mineral fibers, and methods for treating a tissue defect within a patient by applying mineral fibers to the site of the tissue defect.
1. A method for producing a mineral fiber, said method comprising:
(a) contacting droplets of an inorganic liquid-phase mineral precursor comprising an acidic polymer with a crystalline inorganic substrate in an aqueous solution; and
(b) permitting the droplets to deposit onto the surface of the crystalline inorganic substrate, where the droplets coalesce and solidify to form said mineral fiber extending away from the crystalline inorganic substrate.
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31. A mineral fiber produced by the method of
32. A pharmaceutical composition comprising a mineral fiber produced by the method of
33. A method for treating a tissue defect within a patient, said method comprising applying an effective amount of a mineral fiber to the site of the tissue defect, wherein the mineral fiber is produced according to the method of
This application is a continuation-in-part application of U.S. application Ser. No. 10/418,843, filed Apr. 18, 2003, which claims the benefit of U.S. Provisional Application No. 60/373,801, filed Apr. 18, 2002; and this application is a continuation-in-part application of U.S. application Ser. No. 10/691,002, filed Oct. 22, 2003; which are hereby incorporated by reference in their entirety, including all figures, tables, and drawings.
The subject invention was made with government support under a research project supported by the National Science Foundation Grant No. ECS-9986333. The government has certain rights in this invention.
Synthetic bone graft material made to closely resemble natural bone would be a useful replacement for natural bone. Acceptable synthetic bone can avoid the problem of availability and harvesting of autogenous bone and the risks and complications associated with allograft bone, such as risks of infection, disease, and viral transmission.
Natural bone is a composite material consisting of both water and organic and inorganic solid phases. Bone has a hard structure because its organic extracellular collagenous matrix is impregnated with inorganic crystals, principally hydroxyapatite (Ca10(PO4)6(OH)2). Calcium and phosphate account for roughly 65% to 70% of the bone's dry weight. Collagen fibers compose approximately 95% of the extracellular matrix and account for 25% to 30% of the dry weight of bone. The organic material gives bone its flexibility and resilience, while the inorganic material gives bone its strength and rigidity (modulus), and the organization of the two phases provides a high degree of toughness to the composite. A thorough review of bone structure from the angstrom level (mineral crystal) to the micron level (lamellae) has been presented (Weiner, S. et al. [1992] FASEB, 6:879-885).
Surrounding the mineralized collagen fibers is a ground substance consisting of protein-polysaccharides, or glycosaminoglycans, primarily in the form of proteoglycan macromolecules. The glycosaminoglycans serve to cement together the various layers of mineralized collagen fibers. The individual collagen molecules self-assemble to form triple helices, which assemble into collagen fibrils, which then assemble into microscopic fibers. Within the packing of the collagen fibrils/fibers are distinct gaps, sometimes called hole zones. These hole zones are created by the staggered arrangement of tropocollagen molecules (triple helical rods), which leads to periodicity of the hole and overlap zones. Various models have been proposed where these hole zones are completely isolated from each other, or are contiguous and together form a groove. Within these hole zones, mineral crystals form. The mineral crystals in final form nucleate and grow within the fibrils (intrafibrillar mineralization), as well as into the interstitial spaces (interfibrillar mineralization) (Landis, W. J. et al. [1993] J. Struc. Biol. 110:39-54). The mineral crystals in final form are a carbonated apatite mineral (dahllite), but initially may form as an amorphous calcium phosphate phase, which then transforms into the apatite (or possibly via an octacalcium phosphate precursor, which naturally forms plates). The apatite platelets of bone are of nanoscopic dimensions (only a few unit cells thick), and are densely packed into the type I collagen fibrils due to the intrafibrillar mineralization mechanism, and are well oriented with their c-axis (in the [001] direction) parallel to the long axis of the collagen fibrils. Because of the nature of the packing, the orientation of the collagen fibrils will determine the orientation of the mineral crystals (Martin, R. B. et al. [1998] "Skeletal Tissue Mechanics", Springer-Verlag Publishers, New York, N.Y.).
There are numerous biocompatible artificial bone substitutes currently on the market. Of these substitutes, none successfully mimics the composite or microstructure of bone. For example, man-made ceramic composites have some of the desired properties of natural bone (such as matching of modulus), but are notoriously brittle and prone to cracking. By contrast, biological ceramics like bone and teeth resist cracking, with a high toughness and stiffness. It is the nanostructured architecture that leads to mechanical properties that are unique to bone, which are not readily duplicated by polymers (which are not strong or stiff enough), or ceramics (which are brittle and lack toughness, and usually not bioresorbable). These mechanical properties are important because of the body's natural repair processes, in which bone is a living tissue and the cells respond according to the stresses they sense in their surrounding tissue (according to Wolff's Law). If an implant material has too high of a modulus (stiffness), the cells tend to resorb the surrounding bone due to the phenomenon of stress shielding (the stiffer material carries more of the load than the surrounding bone).
A logical choice of materials for a synthetic bone substitute would be a collagen-hydroxyapatite composite; indeed, many have attempted to mineralize collagen in vitro, but the preparation of such a composite has been limited by the ability to achieve the high mineral loading that is attained biologically by intrafibrillar mineralization. An associated periodic contrast pattern is commonly observed by transmission electron microscopy (TEM) of collagen fibers (Carter, J. G. [1990] Skeletal Biomineralization: Patterns, Processes and Evolutionary Trends, Volume 1, Van Nostrand Reinhold Publishers, New York, N.Y.; Hodge, A. J. et al. [1963] "Recent studies with the electron microscope on ordered aggregates of the tropocollagen molecule", in Aspects of Protein Structure, Ramanchandran, G. N. (ed.), pp. 289-300, Academic Press, London, England; Katz, E. P. et al. [1989] Connect. Tissue Res., 21:49-159). From tomographic imaging of naturally mineralizing turkey tendon (which is considered a model of secondary bone formation), there is evidence that the hydroxyapatite crystals first appear within the hole zones of collagen, and then spread throughout the fibrils, leading to the array of iso-oriented nanocrystals of highly organized hydroxyapatite [HAP] embedded within the organic matrix (Landis, W. J. et al. [1993] Structural Biology, 110:39-54; Landis, W. J. et al. [1991] Connect. Tissue Res., 25:181-196). Alternatively, there has been evidence that the collagen fibers contain an amorphous substance during the early stages of bone formation, referred to by Bonnuci as an "inorganic substance in bands" (ISBs), which then crystallizes into the more commonly observed platy crystals (Bonnuci, E. Calcification in Biological Systems [1992] CRC Press Boca Raton, Fla.).
From a materials engineering perspective, the nanostructure of bone is intriguing and can be difficult to define. For example, it is not clear whether bone is more accurately characterized as a polymer-fiber-reinforced ceramic-matrix composite or a ceramic-nanoparticle-reinforced polymer-matrix composite. The two phases are so intimately linked that the mechanical properties are distinctly different than ceramics or polymers, and therefore are difficult to reproduce. To date, scientists do not have a complete understanding of how bone is formed, even at this most basic level of structure. However, it is likely that the nanostructured architecture plays a role in the toughness of bone. Obviously, cellular control is important in biomineralization, and in the case of bone, helps to build its hierarchical structure (i.e., lamellae and osteons), but even the physicochemical mechanism for generating this nano-architecture has not been elucidated. Because intrafibrillar mineralization does not occur simply by attempting to crystallize collagen in vitro using supersaturated solutions of HAP (crystals only nucleate heterogeneously on the surface of the collagen fibers), it is generally assumed that nucleating proteins must be present within the gaps of the collagen fibrils.
It is understood within the biomineralization community that acidic proteins can act as inhibitors to crystal nucleation or growth (Addadi, L. et al. [1987] Proc. Natl. Acad. Sci. USA, 84:2732-2736; Addadi, L. et al. [1992] Angew. Chem. Int. Ed. Engl. 31:153-169; Mann, S. et al. [1983] Structure and Bonding, 54:125-174; Mann, S. et al. [1989] "Crystallochemical Strategies in Biomineralization" in Biomineralization-Chemical and Biochemical Perspectives. Mann, S., Webb, J., and Williams, R. J. P. (eds.), 33-62 (VCH Publishers, N.Y., N.Y.)). In the case of crystal growth, it has been shown that selective inhibition of growth along stereospecific crystallographic planes can lead to a change in crystal morphology (Addadi, L. et al. [1985] Angew. Chem. Int. Ed. Engl., 24:466-485). In at least a few cases, acidic proteins have been shown to promote crystal nucleation (Addadi, L. et al. [1987] Proc. Natl. Acad. Sci. USA, 84:2732-2736; Greenfield, E. M. et al. [1984] Amer. Zool., 24:925-932). It has also been shown that if the inhibitory action of a macromolecule is not complete, certain conditions lead to the induction (stabilization) of an amorphous liquid-phase precursor (Gower, L. B. et al. [2000] J. Crystal Growth, 210(4):719-734), which can have a profound consequence on crystal morphology since transformation of an amorphous precursor does not proceed via the same mechanism as traditional solution crystal growth (Mann, S. et al. [1989] "Crystallochemical Strategies in Biomineralization" in Biomineralization-Chemical and Biochemical Perspectives. Mann, S., Webb, J., and Williams, R. J. P. (eds.), 33-62 (VCH Publishers, N.Y., N.Y.)). Certain features of this polymer-induced liquid-precursor (PILP) process suggest that this mechanism may occur during morphogenesis of calcium carbonate biominerals in invertebrates (Gower, L. A. [1997] "The Influence of Polyaspartate Additive on the Growth and Morphology of Calcium Carbonate Crystals," Doctoral Thesis, Department of Polymer Science and Engineering, University of Massachusetts at Amherst, 1-119).
The present inventors have demonstrated that when the PILP phase is deposited onto an amorphous glass substrate, continuous thin films (˜500 nm thick) of CaCO3 are formed (Gower L. A. et al., "Deposition of Calcium Carbonate Films by a Polymer-Induced Liquid-Precursor (PILP) Process" Journal of Crystal Growth, 2000, 210(4):719-734). Organic substrates, such as type-I collagen, have also been used as substrates on which to deposit the PILP phase, resulting in intrafibrillarly mineralized organic/mineral composites (Olszta M. J. et al., [2003] Connective Tissue Research, 44:326-334; Olszta, M. J. et al., [2003] Calcified Tissue International, 72(5): 583-591). Neither of the previous substrates used were of a crystalline nature and, therefore, epitaxial interaction within the crystallization mechanism was not possible.
The subject invention concerns a mineral fiber that is useful as a biomimetic substitute for bone and other tissues, such as dental enamel, and as filler in paper, paint, coatings, and plastics production. The mineral fiber of the present invention comprises a fibrous mineral phase having a high aspect ratio. The present invention also provides in vitro methods for making the mineral fibers, methods of using the mineral fibers to treat tissue defects, and compositions comprising the mineral fibers.
In one embodiment, the method for producing the mineral fiber comprises contacting an inorganic liquid-phase mineral precursor with a crystalline inorganic substrate under conditions permitting the inorganic liquid-phase mineral precursor to solidify and crystallize, thereby forming the mineral fiber. Preferably, the formed mineral fiber exhibits a single crystalline birefringence and a single crystalline electron diffraction pattern. The crystalline inorganic substrate can comprise any of a variety of minerals, such as calcite rhombs or hydroxyapatite. The mineral can be nucleated on a solid surface. The crystalline inorganic substrate can comprise other mineral compositions suitable for stimulating calcite nucleation from the PILP "flux" droplet. The inorganic liquid-phase mineral precursor preferably comprises an inorganic mineral this is generated by a liquid-phase amorphous-mineral precursor that can be formed by contacting an acid polymer with a mineralizing solution under conditions permitting formation of the inorganic liquid-phase mineral precursor.
Preferably, the acidic polymer contacted with the mineralizing solution comprises at least one member selected from the group consisting of polyacrylic acid, polymethacrylic acid, sulfonated polymer, phosphorylated proteins or peptides, phosphorylated synthetic polymers, sulfated polysaccharides, sulfated glycoproteins, polyaspartic acid, polyglutamic acid, polyaspartate, polyvinyl phosphate, and polyvinyl phosphonate, or combinations of any of the foregoing.
Preferably, the inorganic liquid-phase mineral precursor comprises at least one member selected from the group consisting of calcium phosphate, calcium carbonate, hydroxyapatite, strontium carbonate, barium carbonate, and calcium sulfate, strontium sulfate, calcium oxalate, magnesium-bearing calcium carbonate, and magnesium-bearing calcium phosphate. In other embodiments, the inorganic liquid-phase mineral precursor comprises at least one member selected from the group consisting of hydroxyapatite, octacalcium phosphate, tricalcium phosphate, carbonated hydroxyapatite, fluorinated hydroxyapatite, brushite, magnesium containing hydroxyapatite, dicalcium phosphate dihydrate, and amorphous calcium phosphate.
Biologically active agents can be associated with the fibers of the present invention. For example, the biologically active agent can comprise at least one member selected from the group consisting of medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of disease or illness; substances affecting the structure or function of the body; drugs; antimicrobial agents; antifungal agents; antibacterial agents; antiviral agents; antiparasitic agents; growth factors; angiogenic factors; anaesthetics; mucopolysaccharides; metals; cells; acid mucopolysaccharides; proteins; enzymes, peptides; and wound healing agents.
In one embodiment, the fiber forming method further comprises forming the inorganic liquid-phase mineral precursor by combining calcium salt and an acidic polymer to form an aqueous solution, and reacting the aqueous solution with ammonium carbonate vapor or ammonium phosphate vapor. Optionally, the aqueous solution is reacted with the ammonium carbonate vapor, and the ammonium carbonate vapor is provided through the decomposition of at least one ammonium carbonate material selected from the group consisting of ammonium carbonate monohydrate, ammonium carbonate dihydrate, and ammonium carbamate. In other embodiments, the aqueous solution is reacted with the ammonium phosphate vapor, and the ammonium phosphate vapor is provided through the decomposition of at least one ammonium phosphate material selected from the group consisting of ammonium phosphate monobasic, ammonium phosphate dibasic.
The fiber forming method can further involve forming the inorganic liquid-phase mineral precursor by combining calcium chloride and a combination of acidic polymers to form an aqueous solution, and reacting the aqueous solution with ammonium phosphate vapor or with a phosphate containing solution. In other embodiments, the method involves forming the inorganic liquid-phase mineral precursor by combining calcium salt and a combination of acidic polymers to form an aqueous solution, and reacting said aqueous solution with phosphate generated by enzymatic degradation of phosphate containing compounds. In other embodiments, the method involves forming the inorganic liquid-phase mineral precursor by combining calcium salt and ammonium phosphate, and a combination of acidic polymers to form an aqueous solution, in which precipitation is caused by at least one of the following conditions: a change of temperature, a change of pH, evaporation, or removal of crystallization inhibitor.
The inorganic liquid-phase mineral precursor can be contacted with the crystalline inorganic substrate under various conditions. Preferably, the inorganic liquid-phase mineral precursor is contacted with the crystalline inorganic substrate in an aqueous solution at a temperature of 4� C. or higher. In preferred embodiments, the contacting of the inorganic liquid-phase mineral precursor with the crystalline inorganic substrate involves contacting droplets of the inorganic liquid-phase mineral precursor with the crystalline inorganic substrate, wherein the droplets coalesce and solidify, and wherein the inorganic fiber is formed outward from the interface of the droplets and the crystalline inorganic substrate. The droplets of inorganic liquid-phase mineral precursor include primary droplets that contact the crystalline inorganic substrate and secondary droplets that contact the primary droplets, wherein the secondary droplets extend the length of the inorganic fiber. Preferably, the secondary droplets extend the length of the inorganic fiber in a continuous fashion as a PILP phase is continuously generated through constant composition or batch replenishment techniques. Using the method of the invention, the inorganic liquid-phase mineral precursor can crystallize in an epitaxial orientation.
In one embodiment, the inorganic liquid-phase mineral precursor comprises hydroxyapatite and the inorganic crystalline substrate comprises a hydroxyapatite film.
Typically, the mineral fibers formed using the methods of the present invention have a high aspect ratio (length to diameter) in the range of about 5 (5:1) to 60 (60:1). In some embodiments, the fiber aspect ratio will be in the range of about 10 (10:1) to 60 (60:1). The formed fiber also has a mineral phase that is homogenously distributed throughout the width (cross-section) of the fiber (i.e., not a hollow cylinder). Typically, the mineral fibers formed have a diameter within the range of about 100 nm to 2 μm. Small individual fibers can be grown together in the same direction, thereby forming a fiber bundle of larger diameter (e.g., 100 nm to 1 mm). In some embodiments, the mineral fiber of the present invention does not comprise a metal.
The present invention pertains to mineral fibers and in vitro methods for producing mineral fibers utilizing an inorganic liquid-phase mineral precursor (PILP). According to the fiber forming method of the present invention, the PILP is contacted with a crystalline inorganic substrate under conditions permitting the PILP to solidify, crystallize, and extend away from the crystalline substrate, thereby forming the mineral fiber.
According to the fiber forming methods of the present invention, the mineral fibers typically grow or extend in a substantially unidirectional manner, away from the crystalline substrate (thereby forming substantially linear mineral fibers). When there are fluctuations in the reaction, such as the temperature of the crystallizing solution, the fibers appear to grow in a serpentine manner, much like the serpentine growth exhibited by the fibers produced by the vapor-liquid-solid (VLS) mechanism or solution-liquid-solid (SLS) mechanism when the temperature is varied, as described by Trentler T. J. et al. (Trentler, T. J. et al. [1995] Science, 270(5243):1791-1794; Wagner, R. S. and W. C. Ellis, [1964] Applied Physics Letters, 4(5):89; Wagner, R. S. and W. C. Ellis, [1964] Journal of Metals, 16(9):761).
The inorganic liquid-phase mineral precursor utilized to form mineral fibers of the present invention can be produced using a variety of methods. For example, synthesis of a liquid-phase precursor of calcium carbonate has been described previously (Gower, L. B. and D. J. Odom [2000] J. Crystal Growth 210(4):719-734; Gower, L. A. [1997] "The Influence of Polyaspartate Additive on the Growth and Morphology of Calcium Carbonate Crystals," Doctoral Thesis, Department of Polymer Science and Engineering, University of Massachusetts at Amherst, 1-119; Gower, L. A. and D. A. Tirrell [1998] J. Crystal Growth 191(1-2):153-160), where vapor diffusion of the decomposition products of crushed ammonium carbonate (NH4)2CO3 into a solution containing calcium chloride (CaCl2) is used to slowly raise the supersaturation of calcium carbonate; and one or more short-chain acidic polymer additives is added to induce the precursor mechanism. Alternative methods can be used to gradually raise the supersaturation of the crystallizing solution, including direct addition of a carbonate containing solution to the calcium containing solution; or the escape of carbon dioxide gas from a saturated calcium bicarbonate solution (which is produced by bubbling carbon dioxide into an aqueous solution containing the calcium carbonate salt). Supersaturation can also be raised using temperature, pH, or removal of inhibitory species. Similar methods can be used for the calcium phosphate system, although higher temperature (37� C.) is more favorable for decomposition of ammonium phosphate (or any derivations of ammonium phosphate, such as ammonium phosphate dibasic). The phosphate counterion can be produced using enzymes that cleave phosphate-containing moieties, or through the degradation of phosphate containing phospholipid vesicles such as seen in Murphy and Messersmith (W. L. Murphy, P. B. Messersmith, Compartmental control of mineral formation: adaptation of a biomineralization strategy for biomedical use. Polyhedron 19, 357 (2000)). According to the fiber formation method of the present invention, the crystalline substrate can then be contacted with the liquid-phase precursor of the inorganic mineral, such as calcium phosphate, calcium carbonate, hydroxyapatite, strontium carbonate, calcium sulfate, calcium oxalate, calcium oxide, magnesium-bearing calcium carbonate or phosphate, or any polymorphs of these minerals.
The crystalline inorganic substrate used in the fiber forming method permits epitaxial interaction within the crystallization mechanism. The crystalline substrate can comprise any of a variety of minerals, such as calcite rhombs or hydroxyapatite. It is not necessary that the crystalline substrate be a solid crystal. For example, the crystalline substrate can be a mineral thin film. For example, thin films comprising one or more of CaCO3, CaPO4, BaCO3, and SrCO3 can be used. Preferably, the thin film is a patterned thin film, which allows control of fiber location.
One or more of a variety of acidic polymers, such as acidic short-chained polymers, can be utilized to initiate the amorphous liquid-phase mineral precursor, including different polymers and biological materials. Polyacrylic acid (PAA), polymethacrylates (PMA), sulfonated polymers, phosphorylated proteins, peptides and polymers, sulfated glycoproteins, polyaspartic acid, polyglutamic acid, polyaspartate, polyvinyl phosphate, and blends or copolymers of these materials, individually and in mixtures, can be utilized to induce the liquid-phase separation, for example. A range of polymer molecular weights can be suitable if the other variables of the crystallizing conditions are appropriately modified to generate the PILP phase. Preferably, molecular weights in the range of 2,000 to 15,000 g/mol enhance the ability to induce formation of the precursor.
The methods of the subject invention can be carried out under a variety of conditions. For example, in the case of an aqueous system, the fiber forming method can be carried out at a temperature of about 0� C. to about 100� C. Preferably, the method is carried out at about 4� C. or higher. More preferably, the method is carried out at about 37� C., to match physiological conditions. The method can be carried out at a pH in the range of about 5 to about 10. Preferably, the method is carried out at a pH of about 7.0 to about 7.8 and 1 atm. More preferably, the method is carried out at a pH of about 7.4.
The type of reaction vessel or vessels utilized for producing the mineral fibers of the present invention, or their sizes, are not critical. Any vessel or substrate capable of holding or supporting the PILP and/or crystalline substrate so as to allow the reaction to take place can be used. Preferably, the supersaturation is gradually increased, allowing time for the acidic polymer to induce and stabilize the liquid-phase mineral precursor. It should be understood that, unless expressly indicated to the contrary, the terms "adding", "contacting", "mixing", "reacting", "combining" and grammatical variations thereof, are used interchangeable to refer to the mixture of reactants of the process of the present invention (e.g., acidic polymer additives, calcium-containing solution, and so forth), and the reciprocal mixture of those reactants, one with the other (i.e., vice-versa).
The mineral fibers formed using the methods of the present invention typically have a high aspect ratio (length to diameter) in the range of about 5 (5:1) to 60 (60:1). In some embodiments, the fiber aspect ratio will be in the range of about 10 (10:1) to 60 (60:1). The formed fiber has a mineral phase that is homogenously distributed throughout the width (cross-section) of the fiber (i.e., not a hollow cylinder). Typically, the mineral fibers formed have a diameter within the range of about 100 nm to 2 μm. Small individual fibers can be grown together in the same direction, thereby forming a fiber bundle having a larger diameter (e.g., 100 nm to 1 mm). In some embodiments, the mineral fiber of the present invention does not comprise a metal.
The present invention further concerns a method of treating a patient having a tissue defect by applying mineral fibers of the subject invention (and compositions comprising the fibers) to the site of the tissue defect. As used herein, the term "patient" refers to any human or non-human animal suffering from a tissue defect. According to the method of the subject invention, a therapeutically effective amount of the fibers or composition can be applied at the site of a tissue defect to partially or fully restore structural integrity to the tissue. Once applied, the mineral fibers of the subject invention can function as a filler (or partial filler) or plug, to mend the tissue defect. The amount to be applied will depend upon the size and nature of the tissue defect, and the clinical outcome that is sought. The fibers can be applied within a composition in a malleable form, for example, as a paste or putty, such that the administered composition takes the shape of the bone defect. Alternatively, the composition can be molded pre-cast into a desired shape (such as the shape of the defect) using polymer composition molding methods known to those of ordinary skill in the art, and the molded composition can be administered as a solid or semi-solid article. Thus, the size, volume, thickness, and shape of the molded article can be controlled, as desired. The composition can be applied in particulate form. According to the method of the subject invention, the mineral fibers can be applied so that they directly contact existing tissue adjacent to, or defining, the tissue defect site, or the mineral fibers can be contacting another implant, or both.
The composition of the subject invention (also referred to herein as constructs or fiber constructs or fibrous constructs) can be applied to the tissue defect site as a liquid. Once applied, with a syringe for example, the liquid composition can coagulate or cure ("set") shortly after application to form a solid.
The mineral fibers of the subject invention (and compositions comprising the fibers) can be used as a vehicle for the in situ delivery of biologically active agents. The biologically active agents incorporated into, or included as an additive within, the fibers of the subject invention can include, without limitation, medicaments, growth factors, vitamins, mineral supplements, substances used for the treatment, prevention, diagnosis, cure or mitigation of disease or illness, substances which affect the structure or function of the body, or drugs. The biologically active agents can be used, for example, to facilitate implantation of the mineral fibers into a patient and to promote subsequent integration and healing processes. The active agents include, but are not limited to, antifungal agents, antibacterial agents, anti-viral agents, anti-parasitic agents, growth factors, angiogenic factors, anaesthetics, mucopolysaccharides, metals, cells, and other wound healing agents. Because the processing conditions can be relatively benign (physiological temperature and pH), live cells can be incorporated into fiber constructs during their formation, or subsequently allowed to infiltrate the fibers or compositions through tissue engineering techniques.
As indicated above, cells can be seeded onto and/or within the mineral fiber constructs of the present invention. Likewise, tissues such as cartilage can be associated with the mineral fibers prior to implantation within a patient. Examples of such cells include, but are not limited to, bone cells (such as osteoclasts, osteoblasts, and osteocytes), blood cells, epithelial cells, neural cells (e.g., neurons, astrocytes, and oligodendrocytes), and dental cells (odontoblasts and ameloblasts). Seeded cells can be autogenic, allogenic, or xenogenic. Seeded cells can be encapsulated or non-encapsulated.
Examples of antimicrobial agents that can be used in the present invention include, but are not limited to, isoniazid, ethambutol, pyrazinamide, streptomycin, clofazimine, rifabutin, fluoroquinolones, ofloxacin, sparfloxacin, rifampin, azithromycin, clarithromycin, dapsone, tetracycline, erythromycin, cikprofloxacin, doxycycline, ampicillin, amphotericine B, ketoconazole, fluconazole, pyrimethamine, sulfadiazine, clindamycin, lincomycin, pentamidine, atovaquone, paromomycin, diclarazaril, acyclovir, trifluorouridine, foscarnet, penicillin, gentamicin, ganciclovir, iatroconazole, miconazole, Zn-pyrithione, and silver salts, such as chloride, bromide, iodide, and periodate.
Growth factors that can be incorporated into the fibers and compositions of the present invention include, but are not limited to, bone growth factors (e.g., BMP, OP-1) basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), nerve growth factor (NGF), epidermal growth factor (EGF), insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), platelet-derived growth factor (PDGF), tumor angiogenesis factor (TAF), vascular endothelial growth factor (VEGF), corticotropin releasing factor (CRF), transforming growth factors alpha and beta (TGF-α and TGF-β), interleukin-8 (IL-8), granulocyte-macrophage colony stimulating factor (GM-CSF), the interleukins, and the interferons.
Other agents that can be incorporated into the fibers or compositions of the subject invention include acid mucopolysaccharides including, but not limited to, heparin, heparin sulfate, heparinoids, dermatan sulfate, pentosan polysulfate, chondroitin sulfate, hyaluronic acid, cellulose, agarose, chitin, dextran, carrageenin, linoleic acid, and allantoin.
Proteins that can be incorporated into, or included as an additive within, the fibers or compositions of the subject invention include, but are not limited to, collagen (including cross-linked collagen), fibronectin, laminin, elastin (including cross-linked elastin), osteopontin, osteonectin, bone sialoproteins (Bsp), alpha-2HS-glycoproteins, bone Gla-protein (Bgp), matrix Gla-protein, bone phosphoglycoprotein, bone phosphoprotein, bone proteoglycan, protolipids, bone morphogenetic protein, cartilage induction factor, platelet derived growth factor and skeletal growth factor, enzymes, or combinations and biologically active fragments thereof. Other proteins associated with other parts of human or other mammalian anatomy can be incorporated or included as an additive, including proteins associated with cartilage, such as chondrocalcining protein, proteins associated with dentin, such as phosphoryin, glycoproteins and other Gla proteins, or proteins associated with enamel, such as amelogenin and enamelin. Agents incorporated into the fibers or compositions of the subject invention may or may not facilitate or enhance osteoinduction. Adjuvants that diminish an immune response can also be used in conjunction with the fibers or compositions of the subject invention.
The biologically active agents can first be encapsulated into microcapsules, microspheres, microparticles, microfibers, reinforcing fibers and the like to facilitate mixing and achieving controlled, extended, delayed and/or sustained release. Encapsulating the biologically active agent can also protect the agent against degradation during formation of the fibers or compositions of the invention.
Additionally, the biologically active agents can be pendantly attached to the PILP phase or the formed fibers. The attachment can be facilitated through covalently linking the agent to inorganic phase, or through the use of hydrogen bonding.
In preferred embodiments of the invention, the biologically active agent is controllably released into a mammal when the fibers or composition of the invention is implanted into a mammal, either through degradation in the aqueous environment, or more preferably, due to bioresorption relying on the time scale resulting from cellular remodeling. The fibers or fibrous constructs of the subject invention can be used to replace an area of discontinuity in the tissue in the mammalian body. The area of discontinuity in the tissue can be as a result of trauma, disease, genetic defect, tumor, or surgery, for example.
The compositions of the subject invention can be formulated into a variety of shapes suitable for its function as a tissue implant, such as a plate, pin, rod, screw, anchor, tack, arrow, staple, button, or other regular or irregular shape. The composition of the present invention can be formulated as a three-dimensional scaffold and, optionally, seeded with one or more cell types for implantation within a patient. For example, a hydroxyapatite (HAP) containing PILP can be used to produce fibrous HAP for dental applications. Teeth are composed of various biomineral layers, with the enamel layer being composed of fibrous HAP. Using the mineral fiber forming method of the present invention, the HAP containing PILP can be deposited onto HAP films to produce an ordered array of fibrous crystals for dental applications.
The term "tissue defect", as used herein refers to any tissue deficient region, such as a void, gap, recess, or other discontinuity in the hard or soft tissues. The tissue defect can be artificially or naturally established, and can occur due to disease or trauma, for example. Thus, the tissue defect can occur as a consequence of pathologic, inflammatory, or tumor diseases, surgical interventions, congenital defects, or bone fractures, and the like. Typically, tissue defects in dental applications will be on or within the gum or jaw of the patient's mouth. For example, in the case of certain diseases, such as tumors, the tissue defect is artificially established by removing the tumor tissue. Thus, according to the method of the subject invention, the mineral fibers or compositions containing the mineral fibers can be applied, for example, to repair periodontal defects, for craniofacial reconstruction, joint reconstruction, fracture repair, to conduct orthopedic surgical procedures, and spinal fusion, for example. The term "tissue defect" is also intended to include anatomical sites where augmentation to a tissue feature is desired by the patient in the absence of disease or trauma, such as in elective cosmetic surgery. Thus, the "defect" can be one that is subjectively perceived by the patient, and where augmentation of the bone deficient region is desired.
The term "polymorph", as used herein, refers to inorganic minerals that are similar in chemical composition but have different crystal structures.
The terms "comprising", "consisting of", and "consisting essentially of" are defined according to their standard meaning and may be substituted for one another throughout the instant application in order to attach the specific meaning associated with each term.
As used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a fiber" includes more than one such fiber, and the like. Reference to "an acidic polymer" includes more than one such polymer, and the like.
In addition to their therapeutic applications, the mineral fibers of the present invention may be used as filler in plastics, paint, coatings, and paper production. For example, calcium carbonate is used in a wide range of plastics as a filler, most notably PVC piping. Calcium carbonate fibers of the present invention are particularly useful in these applications because they have high aspect ratios that enhance reinforcement (modulus and strength), and their small size provide excellent surface area for adhesion to the matrix phase. In addition, calcite has a Moh's hardness of 3. In contrast, aragonite, which naturally forms needlelike crystals and is currently the only "fibrous" calcium carbonate available for filler, has a Moh's hardness of 4, making it slightly harder than calcite. Thus, using a fibrous calcite mineral phase would result in less wear on machinery. In addition, unlike the fibers of the present invention, the needle-like shape of aragonite crystals are not in the form of individual fibers, but are packed within spherulitic bundles which are not readily separated as isolated fibers for manipulation into the above composites.
All patents, patent applications, provisional applications, and publications referred to or cited herein, supra or infra, are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.
It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application.
Polymer-Induced Liquid-Precursor (PILP) Process. The preparation of a PILP phase has been described previously (Gower, L. B. and D. J. Odom [2000] J. Crystal Growth, 210(4):719-734; Gower, L. A. [1997] "The Influence of Polyaspartate Additive on the Growth and Morphology of Calcium Carbonate Crystals," Doctoral Thesis, Department of Polymer Science and Engineering, University of Massachusetts at Amherst, 1-119; Gower, L. A. and D. A. Tirrell [1998] J. Crystal Growth, 191(1-2):153-160). The general process introduces the acidic polymer into an aqueous salt solution which is slowly raised in supersaturation. One common method for raising supersaturation is to slowly introduce one of the ionic species, for example using a modified vapor diffusion technique developed by Addadi et al. (Addadi, L. et al. [1985] Proc. Natl. Acad. Sci. USA, 82:4110-4114), in which ammonium carbonate (NH4)2CO3 vapor, produced by decomposition of its powder, diffuses into a solution containing calcium chloride CaCl2 and the acidic polymeric additive. This multistage process is illustrated by the formula:
Alternatively, calcium phosphate (CaP) readily forms an amorphous gel prior to crystallization, which may be contacted with the inorganic crystalline substrate.
Typically, the crystal products are deposited onto a thin glass coverslip (22 mm D.) that is placed in the crystallizing solution, which can then be examined by polarized light microscopy (including in situ examination with ultra-long-working-distance objectives), or gold coated for scanning electron microscopy (SEM). The exact concentration of the reactants can vary.
Formation of Inorganic Crystalline Substrate. Substrate crystals were synthesized in two different manners, which provided calcite crystals of typical rhombohedral habit, but which differed in size and defect texture. For the first set of experiments, micron sized calcite rhombs (20-40 μm) were deposited on glass slides via a vapor diffusion method (Addadi, L., Moradian, J., Shay, E., Maroudas, N. G. and Weiner, S., Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 2732-2736). For comparison, larger, millimeter sized calcite rhombs were grown through a metasilicate gel method. For the first type, glass substrates (22 mm diameter microscope coverslips) were placed into small petri dishes containing 3 ml of a 24 mM CaCl2.H2O (Sigma) solution, and this crystallizing solution was placed in an enclosed chamber (e.g. a desiccator) containing small vials of freshly crushed ammonium carbonate. The carbonate powder decomposes into a vapor (CO2 and NH3) at room temperature, which slowly diffuses into the calcium solution, providing a means for gradually raising the supersaturation of CaCO3. The larger 0.5 mm calcite crystals were fabricated in a gel medium through a controlled chemical reaction method. A sodium metasilicate gel was prepared using 0.5 M CaCl2.H2O (Sigma) in a 0.35 M Na2O3Si.9H2O (Sigma) solution, which was allowed to set in 15 mm dia/127 mm long glass test tubes overnight until gelation. Subsequently, 0.1 M ammonium carbonate solution was added to each test tube and then covered with parafilm. The ammonium carbonate was allowed to diffuse into the gel over a period of 1 month, at which time large calcite crystals were gently removed with tweezers and rinsed several times with deionized water. The larger calcite crystals were analyzed using EDS in order to assure no Si remained on the surface of the crystals. A third manner to make calcite surfaces, tailored to have specific surface density characteristics, can be made following Teng (H. H. Teng, Controls by saturation state on etch pit formation during calcite dissolution. Geochimica Et Cosmochimica Acta 68, 253 (January, 2004)). Briefly, Teng found that by cleaving a large optical-quality Iceland spar (calcite) with a razor blade, to expose the {10-14} face, he could study the surface dissolution kinetics via the addition of solutions undersaturated with respect to CaCO3. He concluded that when the saturation index Ω>0.541 (Ω is defined as the ratio of ionic activity product to solubility product), no etch pit formation was observed, and dissolution occurred at existing steps. When Ω was decreased to 0.541-0.410, pits began to appear and with continuous decrease in saturation allowed for pit density to increase with continued dissolution at step edges. Finally, when Ω was lowered below ˜0.007, there was a sharp increase in pit density.
These observations suggest that the defect texture of calcite crystals can be easily controlled, thereby increasing the fiber density. An alternative means for controlling defect texture is to introduce impurities into the crystals during their formation, such as other inorganic ions or molecular compounds, including polymeric additives.
Formation of Fibrous Crystals. The substrate crystals were introduced into the crystallizing system by placing the glass coverslips which had nucleated the 20-40 μm calcite rhombs (or contained 3 to 4 of the larger gel grown rhombs) in the bottom of a small petri dish filled with 3 ml of a 12 mM calcium chloride dihydrate solution, containing 0.24 mM MgCl2.6H2O or SrCl2.6H2O, along with 200 μg/mL of polyacrylic acid (5,100 M. W., Sigma) to induce the PILP process (Gower, L. B. and Odom, D. J. J. Crystal Growth, 2000, 210:719-734). The Mg2+ and Sr2+, which are routinely found in naturally occurring calcite morphologies, were added because we have determined that they enhance the PILP process (inhibit solution crystal nucleation). CO2(g) was delivered to the sample solutions via the decomposition of crushed ammonium carbonate powder in the same manner as described above for synthesizing substrate crystals. Each of the sample solutions and ammonium carbonate vials were covered with parafilm, into which small holes were punched in order to slowly raise the supersaturation of the calcium carbonate in solution. All components of the reaction were then placed in an enclosed chamber, which allowed diffusion of the carbonate into the solution. Control experiments, containing no polymer, were performed alongside each experiment. For further characterization, the coverslips containing the small rhomb substrate crystals (or individual large gel-grown calcite rhombs) were carefully removed from solution with tweezers and rinsed with ultrapure H2O and then with ethanol (by gently dipping coverslip in a rinse beaker to avoid dislodging the fragile fibers) in order to remove any soluble salts. The glass slides were then examined using an Olympus BX-60 optical microscope in transmission mode, using crossed polars and an optional first-order-red wave plate.
Polarized Optical Light Microscopy (POM) Analysis. Samples were examined on the glass slides in transmission mode using an Olympus BX60 polarized optical microscope with first-order red wave-plate. The wave-plate allows one to observe both amorphous and crystalline phases, which is quite useful for examining crystallization reactions that proceed via precursor mechanisms. In this case, it was also useful for examining the crystallographic orientation of the fibers. Under plane polarized light (PPL), a crystal will appear dark (extinct) under crossed polars when its vibration directions are oriented parallel to one of the polars (indicated as "p" and "a" for polarizer and analyzer direction, respectively). When a gypsum plate is inserted, the crystal in the extinct position will exhibit the same retardation color as the magenta background. Maximum birefringence will occur when the crystal is rotated 45� from the analyzer and polarizer due to constructive interference of the light waves. Calcite is an optically negative material, therefore when the slow vibration direction of the wave-plate (indicated as "sd" double arrow) is parallel with the slow axis of the calcite (indicated by short arrow in NE corner), the combined vibrations will destructively interfere and the fiber will appear blue (a fall in interference color determined from Michel Levy chart). Conversely, the yellow color in the opposite quadrants indicates the slow ray of the crystal is parallel to the slow direction of the accessory plate. This type of analysis allows one to identify if there is a uniform orientation of the crystallographic axes within irregular shaped crystals, such as the fibers described here.
Scanning Electron Microscopy (SEM) Analysis. The samples were dried overnight, fixed to an aluminum stub using carbon paste or double-sided copper tape and then Au/Pd coated. The samples were then examined with either a JEOL 6400 SEM or a JEOL 6335F FEGSEM instrument, both equipped with energy dispersive spectrometers (EDS), at an accelerating voltage of 15 kV.
Transmission Electron Microscopy (TEM) Analysis. In order to examine the fibrous calcium carbonate, the samples were first scratched with a razor blade to dislodge some of the fibers from the rhomb substrate. A small aliquot of ethanol was then dispensed onto the scratched area and immediately drawn up using a micropipette. The removed aliquot was then dropped onto a 200 mesh copper TEM grid coated with thin layers of Formvar and amorphous carbon. The grid was air-dried and subsequently sputter coated with amorphous carbon for stability. The sample was examined on a JEOL 200cx transmission electron microscope at 200 kV in brightfield (BF) and selected area diffraction (SAD) modes.
Fibrous calcium carbonate (CaCO3/calcite) crystals 100-800 nm in diameter were produced at temperatures as low as 4� C. The calcium carbonate fibers were deposited onto calcite rhombs using a mineralization process involving the inclusion of short-chained acidic polymers (e.g., polyaspartic acid or polyacrylic acid) to a supersaturated calcium carbonate system to induce an amorphous liquid-phase precursor. This latter process, documented in the literature, is known as the polymer-induced liquid-precursor (PILP) process. In previous reports, the present inventors have demonstrated that when the PILP phase is deposited onto an amorphous glass substrate, continuous thin films (˜500 nm thick) of CaCO3 are formed (Gower, L. B. and D. J. Odom [2000] J. Cryst. Grow., 210(4):719-734). Organic substrates, such as type-I collagen, have also been used on which to deposit the PILP phase, resulting in intrafibrillarly mineralized organic/mineral composites (Olszta, M. J. et al., [2003] Conn. Tiss. Res., 44:326-334; Olszta, M. J. et al., [2003] Calcified Tissue International, 72(5):583-591). Because these substrates were not of a crystalline nature, there was no possible epitaxial interaction involved in the crystallization mechanism.
In the present experiment, crystalline substrates were used which were synthesized by nucleating 20-40 μm calcite rhombs onto glass substrates. When no polymer was used to induce the PILP process, epitaxial overgrowth of calcite roughened the surface of the existing calcite seeds. CaCO3 PILP droplets preferentially deposited onto the calcite rhombs instead of the glass, but did not form completely continuous films on the faces of the calcite. On a majority of the rhombs, fibrous crystals, which exhibited a single crystalline birefringence, were observed growing from each of the faces. The fibrous crystals were identified as calcite using electron diffraction, and although the diffraction patterns were single crystalline in nature, brightfield (BF) transmission electron microscopy (TEM) images of the majority of fibers showed distinct grains, suggesting that they are polycrystalline with all of the grains aligned in the same orientation. Scanning electron microscopy (SEM) confirmed this polycrystalline nature, as the surface of the fibers appear to be covered in iso-oriented calcite rhombs. It is also possible that these features are microfacets arising from surface reorganization of the energetically unfavorable curved crystals surfaces. In addition, using SEM, enlarged bobbles were observed on the growing ends of the fibers.
The observation of single crystalline fibers growing off of the crystalline inorganic substrates, in combination with the enlarged bobbles at the ends of the fibers, indicates that the process may bear some similarity to existing high temperature crystal growth mechanisms, such as the vapor-liquid-solid (VLS) and solution-liquid-solid (SLS), used to produce nanofibrous semiconductor materials. These processes function through the use of a metal nuclei, which is heated above its melting temperature and placed in an appropriate atmosphere (once the metal has melted, it is referred to as a flux). In the VLS mechanism, a high melting temperature metal is set on a silicon substrate and placed in a vapor atmosphere, whereas in the SLS, a low melting temperature metal is placed in an organometallic solution. Once these metals melt (creating the flux droplet), crystallizing constituents in the atmosphere (vapor or liquid) begin to diffuse into the flux. As a supersaturation of these constituents is reached, crystallization occurs either on the solid surface (VLS) with epitaxial orientation, or with the lowest energy plane forming (SLS) at the flux wall. As long as the temperature is kept above the melting temperature of the metal flux, and the concentration of the crystallizing constituent within the flux droplet is kept constant, the fibers continue to grow, restricted to one dimensional growth by the dimension of the flux droplet containing the reactants.
Using the growth mechanisms as a model, it was hypothesized that the calcite fibers disclosed herein are grown in a similar manner, but without a molten metal flux. Instead, they can be formed in an aqueous solution at low temperature. The amorphous liquid-precursor (PILP) droplets begin to deposit on the mineral face and either solidify or remain partially liquid-like. If the primary droplets solidify, subsequent droplets wick to the side of these droplets and form a film. On the other hand, primary droplets that remain liquid-like can further coalesce with subsequent droplets, at which time the primary droplets in contact with the crystalline surface begin to solidify and crystallize. The top droplet remains a liquid while the bottom becomes solid, thus forcing the fiber outward from the crystalline substrate. As long as the leading "flux" droplet (which appears as a bobble on the end of the fiber) remains as a liquid, the fiber will continue to grow. The mechanism is demonstrated in the schematic of
Enamel, the hardest known vertebrate tissue, is comprised of "rods" of hydroxyapatite tightly packed together in an organized array. Enamel and dentin share a unique starting point, the dentino-enamel junction (DEJ), with the enamel growing away from the DEJ to serve as the mastication surface, and the dentin growing in towards the pulp. While researchers agree that dentine is the first to appear, there is still debate as to whether the enamel epitaxially nucleates from the dentine surface (G. W. Bernard, Ultrastructural observations of initial calcification in dentin and enamel. Journal of Ultrastructure Research 41, 1 (1972).; E. J. Reith, Early stage of amelogenesis as observed in molar teeth of Yorun rats. Journal of Ultrastructure Research 17, 503 (1967).; P. Bodier-Houlle, P. Steuer, J. M. Meyer, L. Bigeard, F. J. G. Cuisinier, High-resolution electron-microscopic study of the relationship between human enamel and dentin crystals at the dentinoenamel junction. Cell and Tissue Research 301, 389 (September, 2000); T. Diekwisch, B. J. Berman, S. Gentner, H. C. Slavkin, Initial enamel crystals are not associated with mineralized dentin. Journal of Dental Research 73, 112 (1994)). Additionally, there are reports that there are poorly crystalline or amorphous regions between dentin and enamel (P. Bodier-Houlle, P. Steuer, J. M. Meyer, L. Bigeard, F. J. G. Cuisinier, High-resolution electron-microscopic study of the relationship between human enamel and dentin crystals at the dentinoenamel junction. Cell and Tissue Research 301, 389 (September, 2000)). These observations led the present inventors to believe that hydroxyapatite fibers resembling enamel can be recreated using a liquid-amorphous mineral precursor deposited upon hydroxyapatite substrates.
Hydroxyapatite crystals can be nucleated on glass slides via direct addition of calcium chloride and ammonium phosphate at 80� C. The CaPO4 PILP process involves using a 1 mM CaCl2.2H2O solution in combination with 200 μg/mL Poly(αβ-DL-Aspartic acid) [Polyasp] and 200 μg/mL Poly(vinyl phosphonic acid) [PVPA]. The glass slides with the hydroxyapatite crystals are placed in the mineralizing solution. This solution is then placed, uncovered, in a desiccator with three equal sized petri dishes, uncovered, and filled with crushed diammonium hydrogen phosphate.
Uncovered is stressed in this explanation because in the CaCO3 PILP process, all of the dishes are preferably covered in such a way to allow diffusion (e.g., covered with parafilm into which three holes are punched). The ammonium phosphate decomposes much slower than the ammonium carbonate; therefore the reaction kinetics have to be increased. The ammonium phosphate slowly decomposes and feeds the counterion into the mineralizing solution. The samples are left to mineralize between 1-4 weeks at which time they are removed from solution and rinsed in both water and ethanol to remove any soluble salts.
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user talexb
That's me on the Great Wall of China, North of Beijing. My [http://www.northernlightschorus.com|chorus] travelled to China in September 2012; a long flight, but most definitely worth it. In 2013, we were the champion chorus at the International Convention held right here in Toronto. Awesome! Plans for 2015 include our annual show at the Toronto Centre for the Arts in March, and a European tour to the UK, Germany and Sweden during the third week of April. Should be a blast!

I'm a Software Developer located in Toronto, Ontario, currently taking a break from Perl to learn everything there is to know about Wordpress plugins for some work I have planned.

Over the summer of 2013, I worked on a few open source projects on github, namely [https://github.com/CPAN-API/metacpan-developer|MetaCPAN] where I updated some docs and wrote some code, as well as [https://github.com/mitchellh/vagrant|Vagrant], where I submitted a first draft of a man page. ([http://www.vagrantup.com/|Vagrant] is an awesome tool, by the way -- you should check it out.) I also updated some docs on [https://github.com/PerlDancer/Dancer2|Dancer2], which I am using to develop an API for a personal project of mine. I also cleaned up the Cookbook section of [cpan://DBIx::Class], removing the code from the POD, instead pointing to the code examples (which I expanded a little). I also contributed a few fixes to the POD in Perl, which appeared in Perl 5.19.4.

At my most recent job, I was under contract with Bluecat Systems, doing some virtualization work using libguestfs to prepare a thinly-provisioned disk image, then using the resulting system via AQEMU and VirtualBox. I also set up a git server and migrated the code base over from Perforce. I also maintained and supported the build process, running Jenkins.

 My LinkedIn profile is [http://www.linkedin.com/pub/3/1ba/511|here]. I'm also on [http://www.twitter.com/talexb|Twitter], and you can also find me on <c>#perl</c> occasionally.

I've been developing software professionally for over twenty five years, starting with a variety of assemblers, then moving up the food chain to C, a sideways trip to Pascal, a brief visit with awk and finally, my current fav, Perl. I've worked in a variety of areas: word processing, data communications, robotics, desktop publishing, pharmacy management, the stock market, document conversion, and foreign exchange.

In the Toronto area and feel liking singing? [http://www.northernlightschorus.com/become-a-member/|Come on out] to a chorus rehearsal and have a listen! Next show: March 28, 2015, at the [http://www.northernlightschorus.com/events/|Toronto Centre for the Arts] in uptown Toronto.
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Limits are made for pushing.
The Smith IOX Interchangeable Goggles push the limits of what goggles can do. Huge peripherals and fog-free vision are packed in with unique space-age style. When you're dropping from the summit, these techy lenses auto-adapt to altitude changes to stop fog ups. Plus, when you're chatting up that hot thing at the midway bar, the I/OX are sure to mesmerize.
- Seamless helmet integration makes your helmet and your goggles one streamlined unit
- Spherical Carbonic-X lens with TLT optics are individually molded to offer you a clear, distortion-free view
- Vaporator Lens Technology uses a Porex filter and a silicone seal to adjust to air pressure and prevent fogging
- Quick-release lens system lets you swap out lenses at lighting-fast speeds
- 5X anti-fog inner lens has a hydrophilic, micro-etched surface to stop fog before it can even start
- Frameless design throws down with wide, unrestricted peripheral vision
- Triple-layer DriWix face foam with fleece lining creates a smooth seal with your face and is insanely soft
- Ultra-wide silicone-coated strap with QuickFit strap adjustment holds these goggles to your head
- Microfiber goggle bag has a replacement lens sleeve to safely get your goggles to and from the mountain
Share your thoughts
What do you think of the
Smith IOX Interchangeable Goggle
? Share a...
Hello I'm 15 and have a pretty large head bigger than my 17 year old brother, would these be ok for me or should i go with the I/O.?
Lance L
Solid Choice
- Familiarity: I've used it several times
I have used these several times in windy, snowy conditions. I like the contrast and definition these goggles provide in flat light. They are a huge improvement over my previous less expensive pair. My favorite feature of these lenses is the lack of fogging while hiking uphill. I recently had them on a 14er and, they performed well.
Great Goggle!!
- Familiarity: I've used it once or twice and have initial impressions
Seems like a well made google. Can't wait to use them next season
Scott G.
- Familiarity: I've used it once or twice and have initial impressions
Black with blackout lens. Great googles. This is my first new pair in about 18 years. I was able to use them on two bluebird days at PCMR and Canyons. I really liked the black tint as opposed to the amber I've always had for bright days. The colors seemed more natural to me which I prefer over other lens colors. No fogging issues in 35-50 degree spring skiing weather and the lenses are fairly easy to change once you get the rhythm down. Unfortunately I didn't get to test the extra red sensor lens.
John L Kleuser
Smiths Goggles
- Familiarity: I've put it through the wringer
I won't ever get another brand of goggles. Smith is where it is at. Super comfortable goggles and the added bonus of a changeable lens.
I definitely recommend these
How its fit with K2 thrive helmet?
These are massive
- Familiarity: I returned this product before using it
Returned immediately, these were massive.
How did I live without these!?
Looking good, feeling great!
Stephen Sugden
Comfortable Powder Protection
These I/OX's are the cat's pajamas. In fact, I think these are so comfortable that you could wear them to bed. I wear these with the Smith Maze helmet. If you are looking for a perfect helmet goggle combo I would grab one of the Smith series helmets. In the photo is the Smith I/OX with the Smith Maze. This combo offers great ventilation as they are designed together to optimize air flow to your goggle lens. I have had no problem with fogging at all. This goggle comes with the bonus lens. I purchased the black/ignitor/extra red sensor. This is the black strap with the ignitor lens and the extra red sensor as the bonus lens. In the photo is the Extra red ignitor lens that I use for low light/overcast days. To top it off, these have a huge field of view. The only hang up to this goggle is that the lens takes a few tries to get quick with the lens change. I was expecting a seamless, easy change out and found that I had to work with it for a while to get it to sit right in the frame. Other then that this is an amazing goggle! Highly recommended.
Hot, but check for helmet integration
- Familiarity: I've used it several times
These work (and look) great with my Smith helmet but I get some push-down with my POC helmet (conversely, my POC goggles work great with the Smith helmet, my Oakley Airbrakes as well). The lens exchange works but is a bit fiddly with fitting the lens into the groove of the rubber-like frame, I found the Oakley Airbrake mechanism easier. Both have great field of view and perform well (no fogging).
Been riding for 18+ years, best product I've ever bought besides my board!
It's like wearing a windshield
- Familiarity: I've put it through the wringer
I bought these last year and love them to death. I am a part time snowboard instructor and put in about 50 days a season on the slopes in all types of weather. I love the ease of changing the lenses and that it came with bright sunny day and low light lenses. I have only had a lense fog up on me once and it was from a hi moisture storm weekend that turned cold before the lense could dry out for the next day.
I can see everything!
- Familiarity: I've put it through the wringer
I love the IOX's... i had previously used the IO goggle and i loved those for many reasons. well the IOX is the same thing, but more! i can change lenses just as easily, i can clean them just as easily and the work just the same, but i can see more! where all goggles have a cut off on what you can see in all directions, the IOX allows you to have a larger sight zone than other goggles before it. because of that, it has to be a little bigger, which makes it a little more breathable when you have the cold stuffy nose days.
Justin Latimer
Really making the great days better !
- Familiarity: I've put it through the wringer
I have used these I/OX goggles in every condition possible and never had them fog up because of how well they vent. Smith really did a great job making these super easy to change on the go but also extremely durable! With a almost endless options in lens colors, it's super easy to find a lens that works for any light condition,even night time ! This is also the first goggle/helmet combo that I can stand to ride in because it fits and vents so well, that I forget I have anything on!
Hey, which helmet do you wear here? thanks.
Sean Zimmerman-Wall
Expand Your Vision and Your Limits
- Familiarity: I've put it through the wringer
Whether its sunny blue bird days making tram laps, tooling around the ranges in a heli, or slogging through knee deep on route, the Smith I/OX is a stellar choice. The massive field of view is excellent for peripheral vision and the lens clarity is unmatched. It is nice that there are so many lens options out there for customizing for conditions. I use the Blackout lens on those intense sunny days and the Red Sensor for cloudy/flat light conditions. I also have a clear lens for night skiing or early morning missions to the gun mount while patrolling. I appreciate how simple the lens changes can be when conditions are variable. I have a small face, and the goggle is still air tight. When coupled with a Smith Helmet, the mirco-climate around your face and head is as comfortable as it gets. You also look like some sort of intergalactic fighter pilot ready to do battle with the mountain. So that is cool.
Seeing is nice!
- Familiarity: I've put it through the wringer
I have every brand from spy to oakley but these are the only ones that don't fog on me! I'm on the snow for usually 10 hours at a time and in every kind of weather condition possible and they preform perfect every time. If you can't see your going to yard sale it hard so they are worth every penny! They also look bad a$$ too
Max Hammer
Rad Goggs
- Familiarity: I've put it through the wringer
Absolutely love these goggs. The frame is big, but not overwhelming. Field of vision is fantastic and the lens change is a breeze (though I usually just run the red sol-x all the time). Venting is on point, and fogging only occurs if your sweating buckets in the cold, not unlike any goggle ever made... The lens varieties are on point, and will surely treat your eyeballs correct. Work great with helmets, I run mine with the Maze or the Gage, and there are no fit issues.
Dave W
Top Gun
- Familiarity: I've put it through the wringer
Excellent goggles with no complaints. The lens swap is the easiest of any interchangeable goggle I've used. I also have the Vantage helmet, and these fit perfectly with it. When wearing the blackout lens, my friends all say I look like a fighter pilot! Flying through the snow, I kind of feel like one too.
Richard Possin
Lens reflection in the Tordrillos, AK
Reflection shot during a break from heli-ski in the Tordrillos, Alaska.
Travis Tzioumis
brrr dude
I/OX with blue sensor mirror (my favorite lens) and Holt helmet on a cold day at the bird.
Lexi Dowdall
Stunning! Simply stunning!
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Fire departments say maintenance is the key to keeping truck on the line
Smaller departments lack money to replace aging fleet
Fire departments outside Evansville may be smaller, but the challenges they face maintaining their fleets are just as forbidding. In some cases, they are potentially crippling.
The Newburgh Volunteer Fire Department's four firefighting vehicles include a 1978 reserve pumper truck Assistant Chief Chad Bennett says should have been replaced 14 years ago, when it reached the typical firetruck's 20-year life expectancy. But the money just wasn't there.
Now, two of the Newburgh department's front-line trucks — a 1993 aerial ladder truck and a 1994 engine, which pumps water from fire hydrants — also are closing in on the 20-year mark.
"We have to have a serious look at getting those pieces replaced because if we don't, and our fleet continues to age, all of a sudden it's going to be like a bomb dropped on us," said Bennett, whose 38-member department covers Newburgh and a portion of neighboring Ohio Township in Warrick County.
"If you can't replace your trucks, you have to increase the amount of money that you put into your vehicle repair and maintenance budget because you know your repairs are going to become more frequent."
But the Newburgh department's $128,234 budget took a 20 percent hit two years ago, as did all town departments, because of state property tax caps and other declining revenue streams that have stressed the finances of all Indiana local governments. It has remained largely frozen since then. Bennett said the department al
ready has cut money for training firefighters and even heating its truck bay.
Newburgh Town Manager Cynthia Burger said local government leaders would love to replace the 1978 truck — but money is a problem.
"Another truck is about $350,000 or so," Burger said. "It's certainly on the radar. It's just that we have to come up with the money."
The prospects for that are murky. The town is the fire department's primary source of operating funds — and the coverage area does not meet income qualifications to receive federal Community Focus Fund Planning Grants available to fire departments.
It is the sort of challenge faced by firefighting agencies in Southern Indiana and everywhere else as they struggle to maintain aging trucks — and newer vehicles that absorb heavy wear and tear.
Area firefighters say careful attention to preventive maintenance is the only sensible way to meet the challenge.
The Princeton Fire Territory, which covers a 69-square-mile area encompassing Patoka Township in Gibson County, is meticulous about maintenance of its 18-vehicle fleet. Good thing, too: The fleet includes a 1981 tanker truck and a 1986 pumper truck. The department held a bid opening late last month on the purchase of a new 3000-gallon tanker to replace the 1981 model.
"Maintenance. Maintenance, maintenance, maintenance," Chief Mike Pflug said.
Among the department's 23 full-time firefighters and nine reservists is a volunteer who works as a mechanic and moonlights part-time on the vehicle fleet. Outside certified emergency vehicle technicians handle any problems that arise with emergency response and electronic portions of the vehicles.
Every Monday, on-duty crews do walk-around inspections of trucks and their equipment.
"It's more or less like they're (the on-duty crews) doing an inventory sheet of the truck and having to check everything as they go," Pflug said. "They start the trucks up, kick the pump in gear, engage and recirculate the pump, check the oil levels, check all the EMS equipment and the loose equipment on the trucks."
Equipment that doesn't check out is tagged and marked for repair. If no spare is available, the truck is taken out of service in favor of one of the department's two reserve engines.
The Princeton Fire Territory employs a Chicago-area company to inspect its two aerial ladder trucks annually, typically a two-day process that involves such tests as hanging weights off the tips of ladders and analyzing oil samples from hydraulic tanks.
The use of out-of-town technicians and inspectors for the required annual certifications is not unusual for area firefighting agencies.
The Mount Vernon Fire Department employs a Northwest Indiana company with a shop in Columbus, Ind., for major repairs and a large and heavily equipped mobile service van for maintenance.
"We'll schedule with them in advance, and they'll come here and spend three or four days doing things like pump testing and changing oil, transmission fluid, doing water, hydraulic and fuel filters, everything we need," said Chief Wes Dixon, whose agency covers a 2.5-square-mile service area within Posey County.
But all the preventive maintenance in the world can't mitigate the fact that firetrucks, like all other vehicles, eventually fall victim to worn out and malfunctioning parts and equipment.
Dixon said the Mount Vernon Fire Department, which has seven full-time employees and 12 volunteers, has been relatively fortunate. Major repair issues have been limited to a cracked cylinder head on a 1989 pumper truck, its first significant repair; and a $17,000 repair to a ladder truck's hydraulic system.
Pflug recalls a $20,000 repair to a Princeton Fire Territory ladder truck when its motor blew up while on scene at a fire.
"What happened there was just one of those freak things that can happen anywhere," he said.
The Newburgh Volunteer Fire Department was forced to lay out more than $5,000 recently when a truck's backup generator system blew up.
The Black Township Fire and Rescue in Posey County paid thousands for repairs when an electrical system burned up on one of its tanker trucks a few years ago, said Chief Jay Price.
"It was just being driven down the road. I believe it was coming back from an incident," Price said.
"There's always that chance of — you don't know. It's just like any other vehicle you drive down the road. You don't know if the motor's going to blow up tomorrow. You just try to keep the best maintenance program you can."
Price's volunteer department, which uses about 40 firefighters, serves those portions of Black Township that are not within Mount Vernon city limits plus a portion of Lynn Township to the north. Its territory is about 135 square miles.
The department's oldest engine is a 1993 model, but Price says firefighters and fire apparatus-certified technicians are as careful and particular about maintenance as any other department.
What separates firetrucks from other vehicles, Price said, is they are driven exceptionally hard.
When time is of the essence, firefighting vehicles don't warm up before tearing out of the station to race to a fire scene. Braking and accelerating are not done daintily with regard to a vehicle's age. Engines and transmissions roar for long stretches of time as pumper trucks remain parked at fire scenes because they have to run to pump water.
"These trucks don't see a lot of miles on them; they're just hard miles," Price said. "They have a lot of RPM going through them.
"A truck might be 30 years old and have only 20,000, 30,000 miles on them, and they're wore out because, I mean, it's hard driving."
Dixon, chief of the Mount Vernon Fire Department, points out that firetrucks are built for heavy service — but that doesn't mean he doesn't do his best to baby one of the region's oldest firefighting vehicles.
"It's a 1968 American LaFrance pumper, and we call it Pop," he said with a chuckle.
The truck, which Dixon called a reserve engine of last resort, is named for the late Frank "Pop" Fessenden, a longtime member of the Mount Vernon department. It backs up pumpers built in 1989 and 1997.
Pop can't pump as much water through as many lines at a fire scene as a newer truck, and its horsepower is comparatively low, considering its older engine design. But Dixon says it is functional.
As is the case in Newburgh, money is the reason Pop hasn't been replaced after more than four decades on the job.
"I trust the truck completely, and it has passed all its inspections, but it wouldn't leave the station for a run unless it was a really major fire or we had more than one fire at a time," Dixon said.
"It has happened a few times."
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Photo, left: Puerta de Viru, Tallinn, EstoniaJOHN BATCHELOR SHOWCo-host: Larry Kudlow, CNBC senior advisor; & Cumulus Media radio Hour OneTuesday 30 June 2015 / Hour 1, Block A: James Pethokoukis, columnist & AEI, in re: . . . Plenty of mainstream Dem economists are talking about major...
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Photo, left: A ballot voting against Themistocles, son of Neocles, under the Athenian Democracy (see ostracism). This text is an example of the epichoric alphabet.JOHN BATCHELOR SHOW Co-host: Thaddeus McCotter, WJR, The Great Voice of the Great Lakes; and author, Liberty Risen. Hour OneMonday 29...
June 28, 2015
Photo, left: Ferguson Rifle; see Hour 4, Gunfight: The Battle Over the Right to Bear Arms in America, by Adam WinklerJOHN BATCHELOR SHOW Hour OneSunday 28 June 2015 / Hour 1, Block A: Justice Brennan: Liberal Champion, by Seth Stern and Stephen Wermiel (1 of 2)Sunday 28 June 2015 / Hour 1, Block...
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Champaign family gives Salt and Light fund drive a big boost
One Champaign family is doing its part to ensure Salt and Light doesn't run out of food again – at least for three weeks this year.
Paul Stancil and Christine Hurt, both University of Illinois law professors, have agreed to sponsor three weeks worth of food at the pantry, one for each of their children.
It's part of a new fund-raising push by Salt and Light, which has seen its traffic almost double since last summer. The pantry ran out of food on May 19 after serving more than 400 families.
It's asking churches, organizations, businesses or individuals to sponsor a week's worth of food for the Wednesday food distribution. The cost has risen 50 percent in the last year, to $1,500, and the goal is to cover 50 weeks, or $75,000.
So far, a half-dozen weeks have been sponsored, said Executive Director Nathan Montgomery.
Stancil and Hurt first got involved with Salt and Light last fall, after seeing the ministry on ABC's "Extreme Makeover" show. They volunteered with their three children – ages 10, 8, and 2 – during the Christmas gift giveaway and at the Wednesday food pantry.
This spring, the children hosted a lemonade stand and raised $255 for Salt and Light.
Given the pantry's recent challenges, Stancil and Hurt decided to become food sponsors, in part because the kids could be involved.
"One of the things we love about Salt and Light is it's more than just a check-writing opportunity, in terms of being able to volunteer and be invested and be face-to-face with the people who are in need," Stancil said. "It's easy to give money and not be engaged with the problem you're trying to solve."
He's surprised by how his children have embraced the effort. The 8-year-old asks, "When can I go back?"
"They like the fact that it's real. They can contribute in some meaningful way, even if it's just sorting clothes in a bin," he said. "It's tough to find a place they can do that and not feel like they're underfoot."
That's the idea of the sponsorship drive, to encourage donors to be part of the distribution "so they can see firsthand the difference that's being made with their contribution," Montgomery said.
On Tuesday, Salt and Light will also launch a "Canless Food Drive," collecting money at local businesses with paint-sized collection cans. Food pantries can buy $100 worth of food for $10 through the Eastern Illinois Foodbank, so a donated dollar goes a lot farther than a can of food, said Ministry Assistant Melany Jackson, who came up with the idea. A trial run at a campus restaurant last December netted $200, and Salt and Light decided to try it on a larger scale this summer, she said.
Graphic designer Jill Kirby donated her services, designing labels that look like a giant Campbell's soup can with "Salt and Light" in place of the company name. Silver Machine of Champaign made the coin slots for the top of the cans.
The cans will be placed at 215 local businesses throughout June.
Besides a United Way grant for a financial literacy program, Salt and Light's relatively modest $245,000 budget is funded entirely by donations. To stabilize its future, the ministry is trying to build up monthly sponsors and created an endowment this year to accommodate possible donation opportunities.
"It's not fun, not being able to help everybody that comes in the door," Montgomery said.
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text: NACS Online / Events / Global Events / Global Forum NACS Global Forum Page ContentDate: March 7-11, 2016 (tentative)Location: Cape Town, South Africa An Exclusive Global Experience That Can Position Your Company for the Future The NACS Global Forum brings together convenience and fuel retailer leaders from around the world for a truly unique experience to connect, exchange ideas and see fresh perspectives in a dynamic, global city each year. Over four days, the program features: Powerful networking and collaboration with global retail leaders including C-level executives from North and South America, Europe, Asia, Australia and Africa. Highly interactive programming including presentations from world-class speakers, roundtable conversations with industry leaders and engaging group discussions with fellow retailers on vital industry topics. Local store tours at diverse retail formats that allow retailers to see what's working in different markets so they can apply new concepts to their stores at home. What Sets the Conference Apart Imagine a comfortable setting in a vibrant city for you to connect, learn from and engage with executives just like you. That's the NACS Global Forum. While there, you'll also be treated to special activities that you might not experience anywhere else. Past events have featured exclusive access and dinner on the field of the Real Madrid fútbol stadium, a special reception in the Sydney Opera House and other exciting, one-of-a-kind experiences that you can share with fellow industry executives. See what's in store for this year's closing reception and dinner. Join Global Leaders in 2015 to Experience Singapore The 2015 NACS Global Forum will take you to exciting Southeast Asia, March 22-26. You'll join industry leaders from around the world to explore the convenience market in the bustling country of Singapore. With a population of just over 5 million and covering less than 300 square miles, this unique city-state features a thriving economy with an unemployment rate of just 2%. You'll see first-hand how the convenience and fuel industry has adapted to one of the world's most unique urban environments. Through store tours at innovative formats, engaging discussions with industry leaders and expert-led presentations on critical business issues, you won't just take away great ideas at the 2015 NACS Global Forum, you'll build concrete strategies for success. Join Us "Attending the NACS Global Forum has allowed me to 'see around the corner' of retailing. By visiting stores in new markets and having the opportunity to network with retailers from around the world I can get a glimpse of what the next retail trends and developments will be. Roy StrasburgerCEO, Convenience Management Services, Inc.United States Quick Links Registration Hotel & Travel Schedule of Events (PDF) Speakers Closing Reception & Dinner Participant List (as of 03/17/2015) Know Before You Go – Singapore Visitor Information See the Experience Hear from retailers around the world and see why attending the NACS Global Forum is a unique experience for you and your company. Global Supplier Council NACS member and non-member retailers from around the world are invited to register for the NACS Global Forum. Supplier attendance is limited to members of the NACS Global Supplier Council.


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It's been a pretty rough week for Lena Dunham as she's attempted to promote her new book "Not That Kind of Girl" overseas.
Following a report from the Truth Report website that alleged the "Girls" actress molested her younger sister Grace years ago, Lena's legal team is taking action.
She's no stranger to controversy, but Lena Dunham is adamant that people know that she never did anything sexually harmful to her little sister Grace.
The "Girls" actress has been under fire after a conservative blog took issue with portions of her new book "Not That Kind Of Girl" in which she recounted being curious about the female body and looking at her sibling's private parts.
She's been trying to promote her new book "Not That Kind Of Girl" but Lena Dunham has hit a serious snag in the form of a new story by TruthRevolt.
The website in question recently ran a story titled, "Lena Dunham Describes Sexually Abusing Her Little Sister," based on an excerpt from her book in which she talks about looking at her sister Grace's lady region.
In addition to promoting her new "Not That Kind Of Girl" book, Lena Dunham is also leading the charge to get more young ladies involved in the political process.
The "Girls" star is featured in a new video for the "Women are Watching" campaign, premiering exclusively on Glamour.com.
Showing some love for her English fans, Lena Dunham showed up at the Secret Garden at Shoreditch House in London on Wednesday evening (October 29).
The green-haired "Girls" star donned a white floral slip dress as she promoted her new book "Not That Kind of Girl: A Young Woman Tells You What She's Learned," signing autographs and posing for photos.
She's been working hard to promote her new book "Not That Kind of Girl," and Lena Dunham decided to change things up with her hairdo before heading up to Canada.
The "Girls" actress posted a photo of her freshly-dyed locks via Instagram, posing alongside her prized pooch Lamby.
For years, celebrities have encouraged young people to engage in the political process, and the latest Rock the Vote video is the hottest yet.
Earlier today (October 7) #TURNOUTFOWHAT dropped a new clip featuring rapper Lil Jon, "Girls" actress Lena Dunham and "Portlandia" star Fred Armisen.
She's no stranger to controversy and Lena Dunham has made quite a name for herself by pushing the envelope with her hit HBO show.
The "Girls" starlet told "Makers: Women in Hollywood," "On Girls, I didn't know if I was necessarily going to get away with casting myself as this lead character. I didn't know if I would get away with some of the just, like, sexual content. I didn't know what was allowed. I just kind of went in thinking everything was allowed, and then it mostly was."


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Neoseeker : Games : PC : Simulation : Flight : JetFighter IV: Fortress Americ... : User Reviews
User reviews for JetFighter IV: Fortress America
8.1 / 10Combined Score
The game just needs a few graphic ajustments, more selectable planes/unlockables and a bigger selection of levels as well to. Not much else to be done.
This game is one of my favorites, I never stop playing it, its so fun I never need to stop playing, so, if you are into combat games, get this first, because this game is a use of free time. This game will knock your socks off! this game will allow you to have fun of a whole nother level! I am proud to of bought this game. And I hope you buy it too! And remember, this game should be on the top of your list for games to get that are very cool!!!!!!!!!!!


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Fun Idea for the Gallery Wall…..
The current issue of Elle Decor featured the Hamptons home of James Huniford. And, while many aspects of this beautifully designed home were of interest to me, I was especially enamoured with this gallery wall he created in a hallway.
Photgraphed by Pieter Estersohn
As the mom of a 2 year old….I am increasingly the recipient of original "art." I suspect this will only increase as Maddie enters preschool in the fall. I think the idea of using clipboards to feature a gallery of art is a great idea. Of course, here Huniford displays a collection of watercolors. In my own home, I could see displaying my daughter's art….enjoying the ability to rotate as she creates new pieces.
I am picturing such a gallery in the mudroom off the kitchen, or perhaps in a playroom. Depending on the location within your home, you could use any number of clipboards as the base of your gallery. Think clear or colored acrylic, a decorative clipboard such as one from this site, or even a vintage clipboard as used in the inspiration photo.
What do you think….would you do this? Any other great ideas for an unconventional gallery wall?