text:
|Publication number
|Publication type
|Application number
|Publication date
|Jun 17, 1997
|Filing date
|Aug 8, 1994
|Priority date
|Aug 8, 1994
|Fee status
|Also published as
|Publication number
|Joel W. Barlow, Goonhee Lee, Richard H. Crawford, Joseph J. Beaman, Harris L. Marcus, Richard J. Lagow
|Original Assignee
|Barlow; Joel W., Lee; Goonhee, Crawford; Richard H., Beaman; Joseph J., Marcus; Harris L., Lagow; Richard J.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (28), Non-Patent Citations (65), Referenced by (187), Classifications (58), Legal Events (8)
|External Links: USPTO, USPTO Assignment, Espacenet
The U.S. government owns rights in the present invention as relevant developmental work was supported by DARPA/ONR (Grant No. N000014-92-J-1394).
A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.
A bibliography of references cited herein is included at the end of this specification. The references listed in the bibliography, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.
1. Field of the Invention
The present invention relates generally to manufacturing methods and systems (collectively referred to as "processes") for the freeform shaping of calcium-containing powders. This invention more specifically relates to processes for shaping bone implants from various calcium phosphate powders and polymer-emulsion binders. Certain embodiments of these processes focus on the use of a Selective Laser Sintering™ ("SLS™") device to automatically and selectively fuse the polymer binder. In such processes, complex three-dimensional objects may be built by selectively fusing successive thin layers of the powdered material.
2. Description of the Related Art
Much attention has been given in the art to the development of materials to assist in the regeneration of bone defects and injuries. In 1926, DeJong observed the similarities between the powder X-ray diffraction pattern of the in vivo mineral and the hydroxyapatite (Ca5 B(OH)(PO4)3, "CHA"). Calcium compounds, including calcium sulfate (Nielson, 1944), calcium hydroxide (Peltier, 1957), and tricalcium phosphate ("TCP") (Albee et al., 1920), have been observed to stimulate new bone growth when implanted or injected into bone cavities (Hulbert et al., 1983). These materials also exhibit good biocompatibility and compositional similarities to human bone and tooth and can serve as resorbable or non-resorbable implants depending on their degree of microporosity.
Some TCP implants are known to be readily resorbable. For example, sintered TCP plugs with pore sizes between 100-200 microns have been implanted in rats (Bhashar et al., 1971). Very rapid bone formation was reportedly observed at three days after implantation, and highly cellular tissue, consisting of osteoblastic and fibroblastic proliferation, was found within the pores. At one week, the size of the implant was reduced, and new bone formation was extensive. After two weeks, connective tissue had infiltrated throughout the ceramic. During the next four weeks, the boney material within the ceramic continued to mature. Electron micrographs indicated that within clastlike cells, ceramic could be depicted in membrane-bound vesicles. The authors concluded that TCP implants were biodegradable, via phagocytosis, the ceramic did not elicit a marked inflammatory response, and connective tissue grew rapidly within the pores.
Similar results have also been reported by Cutright et al. (1972) who also implanted TCP in rat tibiae. In this study, the ceramic cavities were filled with osteoid and bone after 21 days and the TCP implant was no longer detectable after 48 days.
Larger implants in dogs are reported to elicit slower responses. Cameron et al. (1977) found that TCP implants in dog femurs were completely infiltrated with new bone by four weeks. However, after six weeks, the rate of new bone growth had slowed as the TCP was resorbed. Additionally, only 15% of a 2 cm�2 cm iliac TCP implant in dogs was resorbed after 18 months (Ferraro et al., 1979).
Koster et al. (1976) reported the testing of the calcium phosphate formulations monocalcium phosphate, dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate, and combinations consisting of 20% monocalcium phosphate and 80% of either di-, tri- or tetracalcium phosphate as implant materials in dog tibiae. These investigators tested both dense ceramics and porous ceramics with pore sizes between 800-1000 microns. They reported that tissue compatibility is dependent on the CaO/P2 O5 ratio. All materials with ratios between 2/1 and 4/1 are compatible with the optimum ratio being about 3/1 for TOP. After 10 months, Koster et al. (1977) found that tetracalcium phosphate was resorbed only to a minor extent, but that TCP demonstrated lamellar bone growth throughout its pores. Both were found to be tissue compatible. The authors stated that the 3/1 material was not as strong as the 4/1 material and suggested that TCP should be used only in low stress areas while tetracalcium phosphate could be used in high stress environments.
Jarcho et al. (1976, 1977) reported the development of a process for preparing dense, polycrystalline, calcium hydroxyapatite (CHA), with the empirical formula 2(Ca5 (PO4)3 OH) or (3Ca3 (PO4)2)Ca(OH)2. In this study, plugs were fabricated at 100% density and implanted in dogs. No evidence of tissue inflammation occurred, and in contrast to the porous TCP implants described above, little resorption or biodegradation was observed after six months.
Holmes (1979) reported that resorption did occur in porous CHA structures. These results led deGroot (1980) to suggest that all calcium phosphates are degradable (resorbable), but the rate is determined by the degree of microporosity. A dense calcium phosphate with negligible porosity would thus degrade only nominally. These results seem to be verified by Farris et al. (U.S. Pat. No. 4,673,355), who claim biocompatible materials with good properties over the range of Ca/P atomic, or molar, ratios from 0.1 to 1.34. (All patents and patent applications cited herein are incorporated by reference.) These ratios convert to CaO/P2 O5 ratios between 0.2 and 2.68, lower than the 3.0 ratio suggested above. They suggest that the Ca/P or CaO/P2 O5 ratio is not critical for implant applications. Ca/P ratios in the range 0.1 to 2.0 probably show satisfactory biocompatibility. Capano (1987) found that a Ca/P ratio of 0.5, which corresponds to calcium metaphosphate ("CMP"), has the best biocompatibility when implanted in small animals.
As the apatites are nearly identical in properties and chemical compositions to bone and tooth enamel, a considerable amount of synthetic effort has been done in this area. Patents in this area include: U.S. Pat. Nos. 4,046,858; 4,274,879; 4,330,514; 4,324,772; 4,048,300; 4,097,935; 4,207,306; and U.S. Pat. No. 3,379,541.
Several patents describe methods for treating apatite materials to render implantable shapes. These methods of heating and compaction under pressure in molds produce solid porous articles in various shapes. These patents include: U.S. Pat. Nos. 4,673,355; 4,308,064; 4,113,500; 4,222,128; 4,135,935; 4,149,893; and U.S. Pat. No. 3,913,229.
Several patents speak to the use of laser radiation to bond apatite materials to tooth and other surfaces, for example, U.S. Pat. No. 4,673,355 and U.S. Pat. No. 4,224,072.
Other patents describe the use of particulate or compacted apatite in conjunction with various compounds, filler, and cements, for example, U.S. Pat. Nos. 4,673,355; 4,230,455; 4,223,412; and U.S. Pat. No. 4,131,597.
The above discussion indicates that calcium phosphates or compounds, such as CHA that are substantially TCP (Monsanto, for example, markets CHA as TCP), are useful for a variety of bioceramic applications because they are biocompatible and can be fabricated into shapes that have a desirable combination of strength, porosity, and longevity for particular sorbable and non-sorbable needs.
Virtually any calcium and phosphate source can be used to prepare materials of interest. An important issue is the ratio of Ca to P or, as it is usually expressed, CaO to P2 O5, molar ratio in the reactant mixture. For example, one can prepare monocalcium orthophosphate monohydrate from the reaction of CaO with orthophosphoric acid, H3 PO4, as shown in equation 1: ##STR1##
One could also react CHA with H3 PO4 to achieve the same product, as shown in equation 2: ##STR2##
Heating the orthophosphate hydrate can lead to a variety of known products, depending on the firing temperature used, as shown in equations 3-8: ##STR3##
The α-, β-, and δ-forms of calcium metaphosphate are different crystal structures of the same chemical compound that happen to be stable at different temperatures. Tricalcium phosphates can be easily obtained from CHA by simply lowering the Ca/P ratio, as shown in equation 9: ##STR4##
According to Mcintosh et al. (1956), the orthophosphate hydrate can be converted to two crystalline forms by heating, as shown in equations 10-11: ##STR5##
Similar reaction schemes can be written for producing di-calcium and tetra-calcium phosphates from CHA or any other calcium source by reacting with orthophosphoric acid or any other P2 O5 source. The chemical and crystalline forms of the final product are simply set by the Ca/P or CaO/P2 O5 molar ratio and the final temperature.
Five calcium phosphates which exhibit different x-ray diffraction patterns are known to be precipitated from aqueous solution at normal pressure (Van Wazer, 1958). These are Ca(H2 PO4)2, Ca(H2 PO4)2.H2 O, CaHPO4, CaHPO4.2H2 O, and crystalline precipitate of variable composition of hydroxyapatite with the base formula Ca5 (OH)(PO4)3. Various forms of calcium phosphate compounds, Ca/P ratio range from 0.5 to 1, are prepared from the reaction of calcium hydroxyapatite with phosphoric acid.
Thermally dehydrated calcium phosphates are known to form a CaO and P2 O5 binary system. For the CaO and P2 O5 binary system, the chain phosphates appear between the orthophosphate (mole ratio of CaO/P2 O5 of about 3) and metaphosphate (mole ratio of CaO/P2 O5 of about 1) or ultraphosphate (mole ratio of CaO/P2 O5 of less than 1). The metaphosphates, in particular, generally exhibit very high degrees of polymerization and good mechanical properties. In this binary system, with a mole ratio of CaO/P2 O5 less than 55/45, a glass-like structure forms from the melt which has mechanical properties similar to those of natural teeth (Yoshihiro, 1975).
Many studies and methods, from powder compaction sintering to hot isostatic pressing, have been reported for the fabrication of CHA implants. However, sintered CHA materials by conventional techniques are generally as weak as sea coral even at high compacting pressure, because CHA decomposes at temperatures lower than the required temperature for sintering.
Some more recent advances are the development of hydroxyapatite (CHA) and calcium phosphate powders that can be processed to yield porous resorbable bone facsimiles (U.S. Pat. No. 4,673,355); the development of the SLS™ process for directly shaping complex porous structures from thermally fusible polymer/ceramic powders without molds (U.S. Pat. No. 5,076,869); the development of low temperature infiltration and cementing techniques to prepare and replace the polymer binder with ceramic binder (U.S. Pat. No. 5,284,695); and the development of techniques for converting computed tomographic ("CT") information into three-dimensional mathematical files that can automatically guide the SLS™ process (Levy et al., 1992; Levy et al., 1994).
More recent work has been directed at expanding the utility of the SLS™ apparatus by preparing polymer-coated ceramic powders from spray dried mixtures of water, inorganic particulate, and a custom-synthesized, emulsified, nanometer-sized, polymer binder (Barlow, 1992; Vail et al., 1992). Ceramic composites made by this approach are relatively large, 10-50 microns, agglomerates of polymer-coated inorganic particles. These agglomerate powders may spread easily into uniform layers and fuse readily in the SLS™ machine to yield porous "green" parts that have relative densities near 50%, excellent connected internal porosity, and sufficient strengths to be easily handled and shipped. Interconnected pores in bioceramics are often difficult to achieve and are very important in fostering bone growth and for preparing metal matrix/ceramic parts, artificial hips.
Polymethyl methacrylate (PMMA) has also been used to form green composites with alumina and with silica/zircon (U.S. Pat. No. 5,284,695). In this process, an appropriate ceramic silicate colloid is used to infiltrate the connected pores of the polymer-bound green part, the colloid is solidified below the fusion temperature of the binder to maintain part geometry, the binder is then thermally removed and the part fired at typically 1000� C. to form porous, all ceramic parts that are suitable for use as cores and molds for metal castings. Such parts typically have only a 1% linear shrinkage, relative to the green state. Their strengths and porosities can be adjusted by additional infiltration and firing treatments.
Lagow and co-workers have recently described the chemical synthesis of high strength CHA (U.S. Pat. No. 4,673,355) and long-chain calcium polyphosphate bioceramic powders ("CPB") (Capano, 1987; Nelson et al., 1993). CPB powder is a pure calcium phosphate material with condensed phosphate chains (as shown below) with degrees of polymerization often greater than 120. ##STR6##
These materials produce sintered materials that have compressive strengths greater than 200,000 psi and flexural strengths in excess of 20,000 psi. These strengths are about twice that of porcelain used to make dental crowns. Using the Lagow CHA material, Lagow and Friedman have recently completed the first successful, year duration, mandible implant in a canine. Work with CPB implants has demonstrated by electron microscopy backscattering that new bone growth occupied nearly 55% of the volume of a CPB implant in the alveolar (tooth bearing) ridge of a dog, after only four months (Nelson et al., 1993). This rate of resorption and replacement by living bone in CPB is about twice as fast as that in CHA.
The lack of suitable bone replacement is a general problem that can be potentially solved by the development of synthetic bones and bone templates that are converted to bone by the body. Bone banks currently provide gamma radiation-treated cadaver bones for various orthopedic and reconstructive purposes in a world-wide business. Appropriate geometries are not always available from these sources, and there is some concern about the transmission of HIV and other diseases. For example, in connection with spinal fusions, there is a substantial need for wedge materials that can provide support and promote the deposition of additional bone. These needs could be rapidly multiplied, provided viable materials and processes could be developed to readily provide bone materials that are shaped to the needs of each individual patient.
Facial and cranial reconstructive surgery is an area where the need for individual implant geometries is especially critical. At present, such reconstructions tend to be very difficult surgical procedures, typically involving highly skilled grafting with allogenic bone. The method and system of the present invention can be utilized to accurately construct a complete facsimile bone structure, suitable for implantation, employing geometric information that is obtained from either CT data or a Computer Aided Design ("CAD") software package.
The present invention addresses the foregoing and other problems experienced in the art by providing processes for automatically shaping bone implants from various calcium phosphate powders. This invention employs polymeric binder compositions particularly adapted for the formulation of free flowing calcium phosphate/binder composite powders. The powders are suitable for production of bioceramic computer-modeled geometrical implants. Green parts produced in this manner may be post processed to be substantially free of the binder. This invention also allows bioceramic parts to be produced by the low power lasers used in the laser sintering process. The processes may utilize a process called Selective Laser Sintering™ in which complex three-dimensional objects can be built automatically by selectively fusing successive thin layers of powdered material.
One embodiment of the present invention provides a method for making an implant by forming a mixture of a calcium phosphate and a polymer binder, and selectively fusing the polymer binder to form an implant. These steps can be repeated to prepare a multiple-layered implant by successively forming layers of the calcium phosphate and polymer binder mixture, and selectively fusing the polymer binder in that layer and to other adjacent layers to form a plurality of connected layers.
As used herein the term "implant" refers to a device that is fabricated for the purpose of embedding, or placing, within a body. The types of implants encompassed by the present invention include implants suitable for the replacement, repair, or modification of bones, teeth, and the like. However, under certain circumstances it may be conceivable that implants of the present invention may serve other useful purposes.
As used herein the term "selectively fusing" refers to the process of selectively coalescing, or combining, particles such that the formed structure has sufficient strength to be handled and further processed, as desired. The term "selectively" is used to denote the controlled and discriminating fashion with which the fusing process occurs. In this aspect of the present invention, "fusing" refers to the viscous sintering of polymer binder particles that are coating, or otherwise associating with, calcium phosphate particles. This results in a linking of the calcium phosphate particles into a part, which can be further processed by thermally decomposing and removing the polymer binder or by infiltration and subsequent thermal dehydration and the like. This fusing can generally be accomplished selectively by controlling the spatial arrangement of the interconnected particles, for example, with laser sintering processes and the like. Alternatively, the selective fusing could be accomplished using a thermal mask system or by the selective spraying of liquid binders and solvents.
The thickness of the layers formed in this method is preferably from about 3 to about 12 thousandths of an inch. In cases where CT data is employed to shape the implant, the thickness of the layers may be determined by the CT data.
The calcium phosphate is preferably prepared by reacting a mixture of hydroxyapatite and phosphoric acid, although other calcium phosphates can be used. Preferred calcium phosphates include calcium metaphosphate, calcium pyrophosphate, calcium phosphate with from about 25 to about 45 percent by weight calcium oxide, and calcium phosphate with from about 0.5 to about 2 percent by weight sodium oxide, with calcium metaphosphate being particularly preferred.
The calcium phosphate preferably has a mean particle size of from about 5 to 100 microns, with the range of from about 30 to 50 microns being most preferred. Smaller particles tend to produce weaker green parts whereas larger particles can affect the layer thickness and forming.
Certain embodiments of this invention involve coating the calcium phosphate particles with polymeric binders to provide free-flowing powders with advantageous properties for processing into shapes by sintering with a laser beam. The polymeric binder compositions may be employed to mix with, or to coat, ceramic particles to produce free-flowing powders with flow characteristics substantially independent of relative humidity.
The polymer binder may be selectively fused to replicate or form a desired geometrical shape, such as a bone or an enhancement of a bone feature. This desired geometrical shape may be obtained from CT data or CAD software data and communicated to a laser beam by a computer.
The calcium phosphate powder may be mixed with water and a polymer-emulsion binder to form a slurry. In a preferred embodiment, this slurry is rapidly dried by momentarily suspending drops of it in a stream of hot air at a temperature above the fusion temperature of the binder, such as exists in a spray drier or fluidized bed coater. The binder and powder preferably agglomerate and adhere together to form a free flowing composite powder with preferred dimensions in the range of 5-75 μm.
Although it is preferable that the mixture be in the form of agglomerated polymer-coated calcium phosphate particles, mixtures of uncoated calcium phosphate powder and spray dried polymer binder can also be used. Coating the calcium phosphate with the binder is preferred as the polymer binder is used more efficiently in this embodiment, and the coating reduces segregation by density during storing or transporting.
As used herein the term "agglomerated polymer-coated calcium phosphate particles" refers to an indiscriminately formed cluster of particles consisting of calcium phosphate powders that have been coated with a polymer binder. These clusters may be free-flowing substantially independent of the relative humidity.
The implant may be thermally sintered. This can effectively remove the polymer binder, and sinter, or fuse, the calcium phosphate powder.
As used in this aspect of the invention, the terms "sinter" and "sintering" refer to the forming of a coherent bonded mass by heating without melting. In the case of post-processing, the calcium phosphate particles may be combined into a coherent mass with heating, whereas in sintering by laser the polymer binders may be selectively fused by the low energy of the laser beam employed.
Alternatively or in addition to thermal sintering, the implant may be infiltrated with a calcium phosphate solution or the like. This may decrease shrinkage in the implant and also modify the relative density, porosity, and other properties of the implant.
As used herein the term "infiltrating" refers to a process in which a porous implant is placed in an aqueous solution of an inorganic material. This allows the solution to fill the interconnected pores of the implant, and thus upon drying deposit the inorganic material inside the implant. A further thermal sintering step may be undertaken to fuse or coalesce the calcium phosphate.
Preferred polymeric binders include those formed from 1,1-disubstituted vinyl monomers such as esters and amides of methacrylic acid and its derivatives. Examples of 1,1-disubstituted vinyl monomers include methacrylic acid, dimethylamino ethylmethacrylate and methacrylamide, methyl methacrylate and butyl methacrylate. The polymers formed from these monomers are particularly preferred because the major thermal decomposition route is depolymerization to gaseous products in both oxidizing and reducing atmospheres, largely eliminating problems with residual ash.
As used herein the phrase "homopolymer, copolymer, or terpolymer of methyl methacrylate" refers to polymers that are formed by polymerizing methyl methacrylate. These polymers may be formed by the homopolymerization of methyl methacrylate or by polymerizing methyl methacrylate with one or more other monomers.
Another embodiment of the present invention encompasses the implants produced by the previously described methods. These implants preferably have a mean pore size of from about 50 to about 300 microns and a percent relative density of from about 50 to about 80%. As used herein the term "percent relative density" refers to the ratio of the implant density to the calcium phosphate density multiplied by one hundred. As defined, the percent relative density can be used to obtain the percent porosity by subtracting the percent relative density from one hundred.
Another embodiment of the present invention provides a system for making an implant, comprising a mixture of a calcium phosphate and a polymer binder, and means for selectively fusing the polymer binder to form an implant. The fusing means may comprise a laser sintering machine. The system may additionally comprise means for controlling the fusing means in order to form an implant having a desired geometrical shape. This controlling means may be a computer that obtains information about the desired geometrical shape from patient computed tomographic data or Computer Aided Design software.
FIG. 1 is a diagram showing a typical apparatus used in the Selective Laser Sintering™ process employed by certain embodiments of this invention. H is a computer control for a laser source A, focused by mirrors B. Heating is provided by a radiant heater C. D is a leveling mechanism for a powder bed F. G is a new layer being added to the part E being produced.
FIG. 2 is a scanning electron micrograph of calcium hydroxyapatite at 1000 times magnification.
FIG. 3A is an x-ray diffraction pattern for calcium phosphate with 35% by weight of calcium oxide powder. This pattern closely matches that of tromelite, Ca4 P6 O19 (upper small box).
FIG. 3B is an x-ray diffraction pattern for CMP powder (1) as directly prepared and (2) as prepared from a fired 35CaP part that was infiltrated with a calcium phosphate solution and fired again.
FIG. 4 is a photograph of an SLS™ processed craniofacial implant fabricated from CMP powder.
FIG. 5 is a graph demonstrating the effect of the density of a fired and a infiltrated part on the modulus of rupture (three point bending strength).
FIG. 6A is a scanning electron micrograph of a porous surface after firing, shown at 200 times magnification.
FIG. 6B is a scanning electron micrograph of a porous surface after firing and infiltration, shown at 200 times magnification.
FIG. 7 is a scanning electron micrograph of calcium hydroxyapatite which has been reacted with orthophosphoric acid, shown at 1000 times magnification.
FIG. 8 is a scanning electron micrograph of a polymer coated powder, shown at 800 times magnification.
FIG. 9 is a scanning electron micrograph of a sintered surface at 800 times magnification.
Certain embodiments of the present invention provide processes capable of fabricating complex three-dimensional implants made of calcium phosphates. A preferred source of calcium phosphate is from the reaction of hydroxyapatite and orthophosphoric acid. CHA powders are generally very cohesive and consist of very porous agglomerates with mean particle size of 1 to 2 μm and bulk density of less than 0.4 g/cm3 (Hattori et al., 1990). The surface area of such powders determined by Mercury intrusion analysis is about 60 m2 /g, suggesting very small particles. Stoichiometric CHA contains constitutional water in the form of OH- ions. This water can be driven off at 1200� C. In addition, CHA is somewhat hygroscopic and will adsorb water from the atmosphere. This physically bound water forms steam when the powder is heated above 100� C. This interferes with the SLS™ process. FIG. 2 shows the microstructure of finely divided CHA powders.
These powders generally require high sintering temperatures, and therefore typically are not suitable substrates for SLS™ processing. However, coating these powders with polymer binders that can fuse under much milder conditions may alleviate this problem. Such coated particles are shown in FIG. 8 as compared to non-coated particles of CHA which are shown in FIG. 7. As used in this invention, these coated particles may provide excellent substrates for producing bioceramic implants in laser sintering processes. The binder coated calcium phosphate powders may be readily handled, conveniently shipped and may be stored for long periods of time without the separation of components sometimes encountered when using mixed powders. In addition, one may readily produce green parts that can be post-processed to be free of polymer binder.
It is preferred that the polymer be distributed so as to cover as much of the surface of the particulate as possible. In principle, this could be accomplished by dissolving the polymer in a suitable organic solvent to achieve a low concentration of the polymer, depositing the solution on the surface of the particulate, then evaporating the solvent. However, this process has the disadvantage of solvent recovery costs as well as potential environmental harm associated with use of organic solvents. To address this problem, the amorphous polymeric binders preferably are prepared by emulsion polymerization as described in the literature (U.S. patent application Ser. No. 08/279,235 filed on Jul. 22, 1994, which is commonly owned with this application; Vail et al., 1994).
Many polymers can be made by emulsion polymerization. In this technique, liquid monomers are emulsified in water with the aid of an appropriate emulsifying agent. Water-borne, ionic initiators are incorporated to polymerize the monomer, thereby forming the desired emulsified polymer. Emulsion particles are typically quite small, about 100 nm (4�10-6 in) in diameter, so that the polymer is well distributed throughout the water vehicle with concentrations in the range of 2-5�1014 particles per cubic centimeter (Bovey et al., 1955). In general, such emulsions are mechanically stable to the effects of gravity. Emulsion polymerization is generally known to produce high molecular weight products at high polymerization rates and is the method of choice for preparing the polymer binder commonly used in water-based acrylic paint systems.
To be effective in green part production and subsequent binder removal, the polymer binder should soften and flow at temperatures between 40� C. and 100� C. Additionally, the polymer coating should be rigid and non-tacky at room temperature. This reduces "blocking" or premature fusing of the polymer-coated powder during storage and provides some structural permanence (low creep rates and low flexibility at ambient temperature) to composite parts made from this powder.
The polymer's fusion temperature is a function of its molecular constituents. This temperature is characterized by the polymer's glass transition temperature, Tg, if the polymer is amorphous, or by its melting temperature, Tm, if it is semi-crystalline. The compositions employed in the present invention may be prepared from water based emulsions. This places a limit on the number of molecular constituents that are useful to give an amorphous polymer with a Tg in the desired range. An upper limit of 100� C. for the softening temperature is set by the normal boiling point of the water vehicle in the emulsion. Regardless of the process used for coating the calcium phosphate particles with polymer binder, the surface temperature of the particle will be limited to 100� C. as long as a water film is present. The lower limit of the softening temperature may be set to about 40� C. to prevent blocking and creeping at ambient temperatures.
To prevent "fines" that can cause powder spreading problems in the laser sintering processes, it is desirable for polymer flow, film formation, and wetting of the inorganic surface to occur simultaneously with water evaporation. This generally cannot occur if the binder softening temperature greatly exceeds the normal boiling point of water.
Regardless of the polymer or copolymer composition used for the binder, the green strength and agglomerate morphology are related to the binder's ability to rapidly wet the inorganic particle during the coating process. These polymeric binders can be synthesized in emulsion form at controlled viscosity (Vail et al., 1994). The viscosity and the related melt flow index are held in the desired range by the addition of chain transfer agents to the polymerization reactions. The lower viscosity material will have an increased melt flow index, near 30 g/10 min at 200� C. and 75 psi, to optimize the coating characteristics of the polymer binder and the subsequent strength of the green part.
FIG. 1 illustrates an apparatus employed in Selective Laser Sintering™ apparatus. The apparatus includes laser source A, mirrors B, radiant heater C, leveling mechanism D, green part being produced E, powder bed F, new layer G of polymer coated powder, and computer control H. The polymer binder in part E is selectively fused by the action of a low power, rastered, modulated, infrared laser beam A. The preferred type of laser used is dependent on many factors, and in particular the type of powder that is to be sintered. A 25 wattage CO2 laser, typically used to sinter waxes and plastics, generally may be used to sinter the powders of the present invention. The laser beam output of the laser A has a wavelength of 10.60 microns, which is near infrared. In the continuous mode, the laser A can be modulated on or off to selectively produce a laser beam which travels along a specified path. In this manner, the directed laser beam A selectively sinters the powder in the target area to produce the desired sintered layer with the defined boundaries of the desired cross sectional region. This process is repeated layer-by-layer with the individual layers G sintered together to form the green part as shown. It is important to note that in connection with this embodiment the laser beam A fuses only the binder and does not substantially alter or fuse the bioceramic E.
In the illustrated embodiment, the selective fusing is governed by geometric information that is generated by a compatible device at computer control H, such as the CT converter program disclosed with this invention or CAD software. The use of CT scan information permits faithful geometric replication of complex bones to be rapidly and easily prepared by this additive process. In this way, naturally complex bone geometries can be prepared from biocompatible materials that could not be prepared by conventional molding or other fabrication processes. It is also possible to design bones or to modify data from CT scans as might be useful for plastic surgery.
The polymer-bound "green" part E may be post-processed to thermally remove the polymer binder and to sinter and fuse the calcium phosphate powder to prepare bone replicas with a controlled, interconnected porosity. The polymer binder is preferably designed to provide adequate strength to permit handling of the green part, and to debond cleanly without residue. Debonding and sintering can be carried out in a conventional oven that has sufficient capacity to reach the high temperatures required for sintering the ceramic components. Porosity in the final part is a function of SLS™ processing conditions, of oven sintering times and temperatures, and of the original polymer and calcium phosphate type and content in the composite powder.
Post-processing may also encompass infiltrating the implant and then thermally dehydrating the implant. In some current methods of producing prototype parts, water-borne ceramic cementing agents are infiltrated into a polymer bound part previously shaped by laser sintering. The cementing agent is dried and set and the polymer burned out to produce an all-calcium phosphate part. This method of post SLS™ processing has been used to produce other ceramic parts and is described in U.S. Pat. No. 5,284,695. This is generally accomplished at much lower temperatures than post-processing without infiltration. Infiltration can generally accomplished with any inorganic compound or cement generally useful for this purpose. However, where biocompatible implants are desired, it is preferable to infiltrate with calcium phosphate.
Under various circumstances it may also be desirable to sinter the implant thermally and then to infiltrate and thermally dehydrate it. However, infiltration prior to sintering generally results in less shrinkage of the implant.
The polymer binder materials used in the present invention have been developed as thermoplastic binders for ceramic particles, as described in U.S. patent application Ser. No. 08/279,235. The polymeric binders are readily removed from the calcium phosphate compositions by thermal decomposition in oxidizing atmospheres to produce parts that contain only ceramic. In general, the binders are amorphous and polymeric. They are polymers, copolymers or terpolymers having glass transition temperatures above 40� C., and having a melt flow index between about 1 to about 50 g/10 min. at 200� C. and 75 psi extrusion pressure, using the instrument geometry and testing protocols described in ASTM #D1238. Preferred polymer binder compositions include methyl methacrylate and butyl methacrylate. The copolymer of methyl methacrylate and n-butyl methacrylate is particularly preferred as a polymeric binder.
The binders employed in this embodiment of the present invention are different from water soluble binders and slip aids used in conventional ceramics processes in which the binder coated powder is compressed to a shape prior to furnace treatment to remove the polymer and thermally consolidate the ceramic (German, 1990). Such compression is not used in Selective Laser Sintering™ processing; therefore, it is important that coated powders for SLS™ and similar type processing be free flowing at processing conditions.
Additionally, and in a practical sense, water immiscibility of the polymer binder is important. If the binder is too hygroscopic, excess water may create steam during the SLS™ process. This may interfere with or prevent fusion of the binder and substrate into a useful green part. Furthermore, water insoluble polymer binders may permit retention of green shape when infiltrating with water-borne inorganic materials.
Certain binder and binder coating systems may produce a coated particulate that is optimal in size for best performance in the SLS™ process. Particles with diameters from 5 μm to 25 μm have been found to spread, level, and sinter well. Depending on the thickness of the powder layer employed, particles as large as 200 μm (and perhaps larger) can be processed. Lowered bed densities and powder spreading and shear problems may result when particles with diameters smaller than 2 μm are attempted.
The disclosed emulsion polymer binders (typically containing 40% by weight of polymer solids in water) are mixed with calcium phosphate particles to produce a slurry that contains 5-40 vol % polymer when dried. A small amount, typically <1%, of the emulsion of high molecular weight, water-soluble polymer may be added as a suspension aid to help suspend the inorganic particles that are typically 2-150 μm. Typical viscosity of the slurry is kept low, approximately 10-100 poise at room temperature, to facilitate spraying of the slurry.
In one example of a preferred coating technique, the slurry of polymer binder emulsion and particulate is spray-dried in a standard NIRO spray drier equipped with a centrifugal atomizer wheel (Vail et al., 1991). The wheel is usually operated at 35,000 rpm causing a fine mist of the slurry mixture to be slung out into a hot air stream. The water in the mist rapidly evaporates to produce solid particles. Particle size in the range of about 25-50 μm in diameter is preferred. However, by varying the conditions of the spray drying, for example, temperature, feed compositions and atomizer wheel speeds, one can adjust the particle size in either direction (Lefebvre, 1989). The particles obtained are agglomerates of polymer and particulate, as can be seen in FIG. 8. An improperly processed slurry, e.g., where the exit air temperature of the dryer is too low relative to the polymer fusion temperature or where the binder viscosity is too high at the processing temperature employed, may produce a large quantity of smaller, non-agglomerated particles. Such particles do not spread and level as well as the larger agglomerates in the laser sintering processes. For this reason, the Tg or Tm of the polymer binder should be at least 10� C., preferably 15� C. or more, below the exit air temperature of the dryer. Many dryers are operated so that the exit air temperature is near 100�-110� C., and for such dryers and drying operations a Tg or Tm below 80�-90� C. is preferred.
Another preferred coating technique utilizes a fluidized bed dryer that coats the particulate by fluidizing it in a heated gas stream, then spraying the polymer emulsion into the fluidized bed of particles. This coating technique also works well with the disclosed emulsion polymer binders to give uniformly coated particles. Generally, the disclosed binder system may be used in a variety of coating applications so long as such applications incorporate evaporation of the water vehicle near the normal boiling point of water.
Decomposition of the polymeric binder material may be important because in processes used to produce implants, it is desirable to remove the binder material so all-calcium phosphate parts are obtained. Generally, most organic polymeric binders may be oxidized to carbon dioxide and water in the high temperature furnaces normally used to "fire" or sinter ceramics.
Small amounts of other substances may be added to the binder compositions. For example, chemically similar compounds that do not have the requisite structure for depolymerization may be included to enhance adhesion and other desirable properties. Preferably these monomers make up less than about 10 mole percent of the copolymer composition. Typically, this will amount to only a few percent, e.g., 3-5%, depending on the particular polymer and the desired purpose.
CHA was obtained as TCP from Monsanto Inc. and phosphoric acid was purchased from Fischer Scientific in 85% concentration. Poly(methyl methacrylate-co-n-butyl methacrylate) copolymer with a Melt Index of 30.9 g/10 min at 75 psi and 200� C. was synthesized as described in the literature (Vail et al., 1994), and used as a polymer binder in Example 2. UCAR 430 Acrylic Polymer Latex (obtained from Union Carbide Corporation) and PMMA emulsion copolymer (Vail et al., 1994) were investigated as polymer binders in Example 3. Inorganic ceramic cement, Cerama Bind™ 542 was obtained from Aremco Products Inc. This inorganic cement, employed in Example 3, is an alumino-phosphate material that can react to form phosphate bonded CHA material.
The calcium phosphate powders were ground by a Szegvary attritor system, type 1HSA, prior to being mixed with polymer for SLS™ processing. Acceptable ranges in particle size were from 20 to 100 microns in diameter with 30 to 50 microns being preferred.
The mercury porosimeter, Poresizer 9320 from Micromeretics was used to determine the surface area of the powder. The powder samples were heated to expel the absorbed moisture and then stored in a desiccator until analyzed. The sample in a penetrometer was initially evacuated to 25 μHg. Mercury was then admitted and pressure was increased up to 30,000 psi which is capable of measuring pore size of 0.006 μm. A contact angle of 130� was assumed in the calculation of pore size. The particle size distributions of powders were measured by a Coulter Multisizer.
Samples of polymer coated substrates were prepared by spray drying a slurry of emulsion copolymer and calcium phosphate powder according to the following equations that determine the amount of each ingredient: ##EQU1## where mE is the required amount of emulsion, ms the amount of powder to be coated, mw the amount of water to be added, xp is the mass fraction of polymer in the resulting sample, xE the solids mass fraction of the emulsion polymer, xs the total solids mass fraction of the final slurry, φp is the mass fraction of the copolymer, ρp is the density of the polymer, and ρs is the substrate density.
Polymer binders were deposited on the calcium phosphate powders by spray drying a slurry of the calcium phosphate powder and the polymer emulsion employing either a bench scale Pulvis Mini Spray Dryer or a pilot plant scale NIRO Spray Dryer, equipped with a centrifugal atomic wheel. Operating conditions for the NIRO Spray Dryer were 30,000 rpm and an exit gas temperature of 110� C. Alternatively, mixtures were formed by physically mixing polymer binders, which had been spray dried, with the dried calcium phosphate powder.
The SLS™ machine used for this work was a Model #125 (DTM Corp., Austin, Tex.). Polymer coated powders produced by the spray coating method were processed by SLS™ to fabricate the desired green shapes according to the following method. The free-flowing polymer coated powder was loaded into the SLS™ machine for processing. The operating environment temperature was biased to heat the powder bed to just below the glass transition temperature, Tg, of the binder, ˜90� C. This corresponds to a setting of 104� C. on the temperature controller. This controller operated on a temperature feedback signal supplied by an infrared sensor (emissivity=0.90). The sensor indicated the temperature at the powder surface. Overbiasing of the environment temperature was prevented by a thermocouple located just below the surface of the radiant heater. At equilibrium conditions this thermocouple indicated a temperature of ˜119� C. These readings were machine dependent as well as material dependent. The powder bed temperature and the operating environment were allowed to equilibrate for at least 1 hr. The environmental atmosphere was maintained semi-inert (O2 <8%) by N2 purge.
Sintering of the polymer coated powder was accomplished using a modulated, CO2 laser beam using scanning conditions prescribed in the actual experiments. The parameters, except the layer thickness, can be combined to give the applied energy density defined as: ##EQU2## where AN is the applied energy density, P the laser output power, BS the beam scan speed, and SCSP the scan line spacing. When expressed in the given units this number had values generally less than 10.0 cal/cm2. Parts exhibiting acceptable green strengths were produced with AN >0.5 cal/cm2. This lower limit appeared to be constant for most material systems. Typically, parts were produced with AN values of about 2 to 2.5.
The CT data image of human temporal bones was received from a GE 9800 CT scanner as a series of slices, nominally 1.5 mm thick. Each slice consisted of a raster image of the temporal bone; the resolution of each image was 256�256 volume elements, or voxels. Each voxel was 2.5 mm2 and was represented as a floating point number indicating the average density of the tissue at that voxel location. The density is measured in Hounsfeld units, representing the ratio of the tissue density to the density of water. Density values ranged from -1000 to 3095. The SLS™ process required boundary information rather than interior density data; therefore, a conversion process was necessary.
A computer program was written to convert the raster images to contour images of the temporal bone slice in each plane by specifying a minimum threshold density below which the data could be ignored. A source code listing of this program is appended at the end of this specification. The threshold value was selected manually by a CT technician and provided as input. The program then scanned each row in the raster image to locate changes in density that crossed the threshold value provided. These changes represent the bone contour outline. Each voxel at which the threshold crossing is detected is converted to a laser toggle point location by simple translation and scaling transformations. The parameters for this conversion are based on the known size of the sample. The toggle point information was then written in a file in the correct format for direct processing by the SLS™ machine.
In cases where the thickness did not coincide with the thickness required for the SLS™ process (typically 0.005 to 0.01 inches), the SLS™ control compensated for this by either skipping layers (for thinner layers) or replicating layers (for thicker layers).
The thresholding software was implemented in the C programming language on a Sun Microsystems SparcStation 2 workstation with the UNIX operating system. The implementation is independent of the hardware and could be ported to other stations.
This experiment illustrates the fabrication of complex and delicate bone shape parts from CT data using a Selective Laser Sintering™ process. In order to make denser porous implants, calcium metaphosphate powder that has been mixed with polymer binder and SLS™ processed was either heated at high temperatures for long periods of time, a procedure that increased shrinkage and geometric inaccuracies, or heated at lower temperatures for shorter periods of time to lightly sinter the part followed by infiltration with a calcium phosphate solution, drying, and refiring at a lower temperature to produce a calcium ultraphosphate glass-bound calcium metaphosphate structure. Alternatively, a part made from a calcium phosphate powder that contained a higher Ca/P ratio than CMP, e.g., tromelite (referred to herein as "35CAP"), was infiltrated with a calcium phosphate solution and fired to produce a calcium metaphosphate-bound structure that had better physical properties, low shrinkage and higher density. It is also possible to infiltrate with a calcium phosphate solution prior to the first heating to remove polymer and sinter the part.
Complex bone shapes, such as that shown in FIG. 4, required green strengths near 150 psi to permit ordinary handling. This craniofacial image, composed of 27 different layers, was created from CT scans of a human temporal bone (Levy, 1992). This part was approximately four inches long and one and half inch thick with well defined cavities.
(1) Calcium metaphosphate ({Ca(PO3)2 }n, "CMP")
CHA (251 g) was reacted with a solution of 85% phosphoric acid (403 g) in water (150 g) at room temperature, pursuant to equation 14. The prepared paste was dried at room temperature and then heated to 150�-200� C., pursuant to equation 15. ##STR7##
The reaction product was confirmed by the x-ray diffraction analysis. Powder that was heated to 150� C. exhibited the x-ray diffraction pattern of a mixture of Ca(H2 PO4)2 and Ca(H2 PO4)2.H2 O. This powder was further dehydrated to β-calcium metaphosphate (CMP), pursuant to equation 16, which is theoretically composed of 28 wt % of CaO and 72% of P2 O5 and reported to have an average chain length of 10,000 (Corbridge, 1990). The x-ray diffraction pattern of CMP made by the described method is compared to the standard pattern in FIG. 3B. ##STR8## (2) Calcium pyrophosphate (Ca2 P2 O7, "CPP")
CPP was prepared from reacting CHA (251 g) with 85% phosphoric acid (196 g) in a manner analogous to that described for the preparation of CMP. ##STR9## (3) Calcium phosphate with 35 wt % of CaO ("35CaP")
CHA (251 g) was reacted with 85% phosphoric acid (251 g). X-ray diffraction pattern of this powder, as shown in FIG. 3A, was identified by JADE x-ray peak identifying program as mixture of major phase of 4CaO.3P2 O5 and minor phase of CPP, "tromelite".
(4) CPP with 1 wt. % of Na2 O ("1NaCPP")
The prepared CPP powder was mixed with 1 weight percent of Na2 O (by addition of 1.7% by weight of Na2CO3) to depress the melting temperature in order to study the influence of surface area of the powder on green strength. 1NaCPP was thermally coalesced at 1020� C. and then ground in the attritor. The ball milling time was controlled to have different particle size and consequently surface area. Three samples of pore surface area, 1.8, 1.4, and 1.1 m2 /g, were measured by mercury porosity.
In the powder preparation step, a firing temperature of 900� C. was sufficient to coalesce CMP, melting point of 985� C. However, for 35CaP powder, which had a higher melting temperature 900� C. was not high enough to coalesce the powder. The resulting powder had a very high surface area but the green parts had only 40 psi strength with 15% by weight of polymer binder. This reasoning was verified when CPP powder, fired at 1300� C. for 2 hours, then ground in the attritor and classified to a mean diameter of 30 μm, showed good green strength, whereas the powder fired at 900� C., ground to a mean diameter of 2 μm, showed barely any green strength. Also, 1NaCPP powder with a surface area of 1.8 m2 /g exhibited poor green strength, while the powder with a surface area of 1.4 m2 /g showed very good strength. Both powders were mixed with 15% polymer binder by weight.
The appropriate powder was physically mixed with 15% by weight (30% by volume) of spray dried polymer, poly(methyl methacrylate-co-n-butyl methacrylate) copolymer, and SLS™ processed with the conditions shown in Table 1.
TABLE 1______________________________________SLS ParametersPower Scan Space Beam Speed Layer thickness Bed Temp.(W) (mil) (ips) (mil) (�C.)______________________________________7.5 5 25 5 90______________________________________
The SLS™ processed CMP green parts had a density of about 0.91�0.03 g/cm3, 33% of the theoretical density, with the fracture strength of 130�20 psi. This was sufficient to permit rough handling of complex bone shapes, such as that shown in FIG. 4.
However, 35CaP green parts had a density of 0.83 g/cm3 with a fracture strength of 40�10 psi. This relatively low strength of the latter parts was attributed to smaller particle size and, consequently, higher surface area of this powder than that of the CMP powder.
Three methods to process the implants after they have been formed by laser sintering are: (1) thermal sintering, (2) thermal sintering to set implant and then infiltration/dehydration/sintering, and (3) no thermal sintering prior to infiltration/dehydration/sintering. The first method involved firing the implant for several hours at sintering temperatures, roughly 800�-1600� C., depending on the calcium phosphate composition used. This approach produced the highest strength materials. However, the firing step caused the part to shrink, which may not be desirable for construction of an accurate facsimile bone structure from geometric information obtained from patient CT data. Furthermore, the shrinkage was not isotropic. Linear shrinkage in thickness was much larger than that in width or length, due to the nature of layer-wise construction of parts in SLS™ process.
The second approach was accomplished either by sintering the implant for a reduced period of time, and then infiltrating and dehydrating the implant and heating to the melting point of the infiltrant to sinter the part. This approach allowed the implant's density and strength to be increased relative to an implant with the same sintering conditions but no infiltrant. The implant also shrank much less than in the direct thermal sintering approach. However, the implant exhibited less green strength as a function of density, as shown in FIG. 5.
The third approach to reduce shrinkage is to infiltrate the implant and then thermally dehydrate and sinter it without a previous firing step (U.S. Pat. No. 5,284,695). This may decrease the amount of shrinkage and green strength even more.
Another issue that affects the choice of post-processing method is the resorbability of implant desired. The resorbability is a function of the density. Therefore, by adjusting density, perhaps by filling the pores with calcium phosphate, the resorbability of the implant can also be adjusted.
Due to the severe restriction imposed on the selection of a cement for biomedical applications, a calcium phosphate solution was chosen as the infiltrant in this experiment. For effective penetration through the pore, the calcium phosphate should to be dissolved completely in a biologically acceptable media.
(1) Thermal Sintering Method
The green parts were fired up to sintering temperature to remove the polymer and subsequently sinter the calcium phosphate. The temperature was raised at an average rate of 16� C./min up to 500� C. and then raised slowly to 880� C. The parts were held at 880� C. for 2 hours and cooled down slowly. During the firing, the parts were kept in lightly packed CHA powder to help maintain the shape and provide even heat distribution to reduce curling. CHA was chosen as the packing material due to its low bulk density, less than 0.5 g/cm3, and high melting temperature.
CMP green parts were fired at 880� C. for 2 hours. The fired CMP parts showed a 3 point bending strength of about 400 psi and a density of about 0.97 g/cm3, corresponding to a 17% volume shrinkage. A strength of about 2700 psi was obtained by firing a CMP part at 940� C. for 1 hour with a density of about 1.4 g/cm3.
(2) Infiltration/Dehydration/Sintering after Thermal Sintering Method
Parts were sintered as described above, and then infiltrated with a calcium phosphate solution. Calcium phosphate paste was prepared by mixing CHA and phosphoric acid which was then diluted with water to form a slurry. The prepared slurry was dissolved in boiling water. It was found that 15g of CHA with 60g of 85% phosphoric acid was a good composition when dissolved in boiling water to make about 120 ml of solution.
Infiltration was performed mainly by capillary action by placing the implant in the solution. After the pores were saturated with infiltrant, the parts were taken out of the solution and allowed to dry at 50� C. and then fired at the appropriate temperature according to the expected final Ca/P ratio. It was found that when the pores were saturated upon infiltration, the resulting weight gain was inversely proportional to the initial density.
The polymer free parts with a density of about 0.97 g/cm3 were infiltrated as described earlier. For the CMP parts, a first infiltration resulted in 31�2% weight gain after firing 725� C. and strength of 1100 psi and subsequent infiltration increased the density about 50% and strength about 1500 psi. Strength vs. density data are shown in FIG. 5. Further infiltration caused the parts to melt and deform inhomogeneously at 725� C., which could indicate existence of a Ca/P concentration gradient through the part. This also lowered the strength of the part. The fractured surface of this part showed randomly distributed vitrified parts. It is believed that infiltrant filled up the pore and formed a phosphate glass.
The formation of phosphate glass was verified in a separate experiment. In this experiment, the calcium phosphate solution was heated to 600� C. where it formed a nonporous transparent glass that contained 15.7% CaO. As additional proof, the infiltrated part was ground to a powder for x-ray diffraction analysis. There was no significant difference in x-ray patterns before and after infiltration. This indicates that no new crystalline phase had been formed.
A 35CaP green part was fired for 2.5 hours at 880� C. to achieve a lightly sintered structure. The structure showed a 40% weight gain upon first infiltration with a calcium phosphate solution due to its lower density. This part was dried and then heated to 725� for longer than 6 hours. Further infiltration increased the strength to about 4200 psi and a relative density of 57%, density of 1.6 g/cm3.
X-ray diffraction analysis indicated that the initial powder, which was a mixture of major phase of 4CaO.3P2 O5 and minor phase of CPP, was converted to calcium metaphosphate after post processing. FIG. 3B shows this phase transformation. The morphology of the fired and infiltrated fracture surface are shown in FIGS. 6A and 6B. Infiltration caused more necking between the grains. The pores were well interconnected and the pore size was approximately larger than 50 μm.
This experiment details preliminary efforts to fabricate implants from calcium hydroxyapatite reacted with orthophosphoric acid. The strengths of the sintered materials in this example were found to be very low.
The failure of this experiment has been ascribed to the lower temperatures of the reaction of the CHA and orthophosphoric acid. In this case, the calcium phosphates were not converted to the more stable meta- and pyro-phosphates but were instead hydroxyapatite hydrates. When these compositions were processed with laser sintering, they were converted to the meta- and pyro-phosphates with the concomitant production of steam. This water was very detrimental to the formation of the implants. Therefore, implants with acceptable green strengths, densities and porosities were not produced.
This example demonstrates that the calcium phosphates of the present invention must be prepared at high enough temperatures prior to SLS™ processing to not decompose during such processing to produce water.
To determine the required amount of polymer binder, the coated powder was heated in air to 150� C. to fuse the polymer. Afterwards, the powder was cooled and qualitatively examined. More than 20% (45 vol. %) of UCAR 430 was required to produce a cake that barely permitted handling. While polymethyl methacrylate copolymer coated materials showed better properties at 20% coating, cakes were still easily crumbled. These problems were attributed to the high surface area of the finely divided CHA powder.
In an attempt to modify surface area, CHA (50 g) was reacted with orthophosphoric acid (H3 PO4) (100 ml, 5M), and heated to 150� C. to form a cake. The cake was then ground back to a finely divided powder. The morphology of the reacted CHA powder is shown in FIG. 7. The powder was spray dried with 14% by weight (30% by volume) of polymethyl methacrylate polymer and examined. The oven sintered cake showed significantly improved strengths, enough to permit rough handling.
Based on the oven tests, the coating of the CHA powders with the 14% of PMMA copolymer was scaled up by using an Anhydro Laboratory Spray Dryer (Vail et al., 1991). The operating conditions were as follows:
______________________________________Slurry solids content: 45 wt. %Inlet temperature: 175� C.Outlet temperature: 110� C.Atomizer speed: 30,000 rpm______________________________________
FIG. 8 shows the scanning electron micrograph of a polymer coated powder. Spray dried powders were SLS™ processed employing the operating conditions presented in Table 2.
TABLE 2______________________________________Operating conditions of SLS ™ machine.Power Bed Temp. Layer Thickness Scan Space Scan Speed(W) (�C.) (mil) (mil) (inch\sec)______________________________________5 120 8 5 15______________________________________
SLS™ processed parts were infiltrated with a phosphoric acid based inorganic cement. High surface tension was observed upon infiltration which prevented effective penetration by the cement, Cerama Bind™. Methanol and Witcolate D51-51 surfactant (Witco Corporation) were used to reduce the surface tension. Infiltrated green parts were dried for 5 days under ambient conditions. Upon drying, the parts were cured in the oven, at 200� C., raised from ambient temperatures at a rate of 50� C./hr. As a final step, green parts were fired up to 700� C. in the furnace for 2 hours to burn off the polymer.
Oven tests showed that parts made with polymer coated non-reacted CHA could not achieve acceptable green strengths. Low bulk density, due to very large specific surface area caused by very small particle sizes and large porosity, is believed to be the reason for this behavior, although the hygroscopic nature of the CHA could be a contributing factor.
While CHA in its pure form has a bulk density of less than 0.4 g/cm3, CHA reacted with 5M phosphoric acid shows increased density to over 0.7 g/cm3. SLS™ processed parts made of reacted CHA had sufficient strengths for rough handling as oven tests of the sintered cakes predicted. The strengths of post-processed bioceramic parts were even higher. FIG. 9 shows a fractured surface of a part that was post processed and fired.
While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the systems, compositions, methods and in the steps or in the sequence of steps of the methods described herein without departing from the concept, spirit and scope of the invention. For example, it will be apparent that certain agents which are chemically, compositionally and functionally related may be substituted for the agents described herein where the same or similar results may be achieved. All such similar substitutes and modifications apparent to those skilled in the art are considered to be within the spirit, scope and concept of the invention as defined by the appended claims.
U.S. Pat. No. 3,379,541 to Tuvell (1968).
U.S. Pat. No. 3,913,229 to Driskell et al. (1975).
U.S. Pat. No. 4,046,858 to Barsa et al. (1977).
U.S. Pat. No. 4,048,300 to Tomlinson et al. (1977).
U.S. Pat. No. 4,097,935 to Jarcho (1978).
U.S. Pat. No. 4,113,500 to Ebihara et al. (1978).
U.S. Pat. No. 4,131,597 to Bluethgen, et al. (1978).
U.S. Pat. No. 4,135,935 to Pfeil et al. (1979).
U.S. Pat. No. 4,149,893 to Aoki et al. (1979).
U.S. Pat. No. 4,207,306 to Jarcho (1980).
U.S. Pat. No. 4,222,128 to Tomonaga et al. (1980).
U.S. Pat. No. 4,223,412 to Aoyagi et al. (1980).
U.S. Pat. No. 4,224,072 to Steward (1980).
U.S. Pat. No. 4,230,455 to Hidaka et al. (1980).
U.S. Pat. No. 4,274,879 to Irvine (1981).
U.S. Pat. No. 4,308,064 to Takami et al. (1981).
U.S. Pat. No. 4,324,772 to Conn et al. (1982).
U.S. Pat. No. 4,330,514 to Nagai et al. (1982).
U.S. Pat. No. 4,673,355 to Farris et al. (1987).
U.S. Pat. No. 5,076,869 to Bourell et al. (1991).
U.S. Pat. No. 5,284,695 to Vail and Barlow (1994).
U.S. patent application Ser. No. 08/279,235 filed Jul. 22, 1994 by Barlow et al.
Albee et al. Ann. Surg., 71:32-39, (1920).
Barlow 3rd International Conference on Rapid Prototyping, pp. 73-79, (1992).
Bhashar et al. Oral Surg., 31:282-289, (1971).
Bovey et al. Emulsion Polymerization, Interscience Publishers, Inc. , 1, (1955).
Cameron et al. J. Biomed. Materials Res., 11:179-186, (1977).
Capano The chemical synthesis and biomedical and dental applications of the first truly successful in vivo replacements for bones, teeth, and similar materials, Ph. D. Thesis, University of Texas at Austin, (1987).
Corbridge Phosphorous: an outline of its chemistry, biochemistry and technology, Elsevier, 224, (1990).
Cutright et al. Oral Surg., 33:850-856, (1972).
deGroot J. Biomaterials, 1:47-50, (1980).
Ferraro et al. J. Dent. Res., 58-A:410, (1979).
German Powder Injection Molding, Metal Powder Industrial Federation, (1990).
Hattori et al. J. Am. Ceram. Soc., 73(6) :1803, (1990).
Hill et al. Amer. J. Sci. 242:457-477, 542-562, (1944).
Holmes Plast. Rec. Surg., 63: 626-633, (1979).
Hulbert et al. "History of Bioceramics", in Ceramics in Surgery, Vincenzini, ed., Elsevier: Amsterdam, 3-27, (1983).
Jarcho et al. J. Materials Science, 11:2027-2035, (1976).
Jarcho et al. J. Bioeng., 1:79-92, (1977).
Koster et al. Langenbeck's Arch. Chir., 343:172-181, (1977).
Koster et al. Langenbeck's Arch. Chir., 341:77-86, (1976).
Lefebvre Atomization and Sprays, Hemisphere Publishing, (1989).
Levy et al. Am. J. of Neuroradiology, 15:473-477, (1994).
Levy et al. Solid Freeform Fabrication Symposium Proceedings, 3:161-173, (1992).
Mcintosh et al. Anal. Chem., 28(9):1424-1427, (1956).
Nelson et al. J. Oral & Maxillofacial Surg., 51:1363-1371, (1993).
Nielson, A.; Acta Chir. Scandanav., 91:17-27, (1944).
Peltier et al. Ann. Surg., 146:61-64, (1957).
Vail et al. J. Appl. Polym. Sci., 52:789-812, (1994).
Vail et al. Solid Freeform Fabrication Symposium Proceedings, 3:124-130, (1992).
Vail et al. Solid Freeform Fabrication Symposium Proceedings, 2:195-205, (1991).
Van Wazer Phosphorous and Its Compounds, Interscience Publisher, 1:517-522, (1958).
Yoshihiro Shika Rikogaku Zasshi, 16:196-202, (1975).
______________________________________/***********************************************************# Section Name :newimage.c *# Resp. Engineers :Suman Day and Sashidhar Guduri# Description :Program to convert CT scan data to# toggle point format************************************************************# Included Functions************************************************************# Current SCCS Version:1 *************************************************************# Revision History# 1.1 on 5/2/1992*********************************************************** /#include <stdio.h>#define TRUE 1#define FALSE 0main(argc,argv) mainint argc;char *argv[];unsigned short inbuf[512];unsigned short outbuf[1024];FILE *infp;int i; /* pixel count */int j; /* scanline count */int k;int flag;unsigned short eol = Oxfffe;flag = FALSE;if (argo = 2){if((infp = fopen(argv[1],"rb")) == NULL) { fputs("open failed",stdout); exit(0); }for(j=0;j<512;j++) { k = 0; fread(inbuf,sizeof(unsigned short),512,infp); for(i=0;i<512;i++) }if(inbuf[i] > 1224) { if(flag == FALSE) { outbuf[k] = j; outbuf[k+1] = i; k = k + 2; flag = TRUE; } else { if(flag == TRUE) { outbuf[k] = j; outbuf[k+1] = i; k = k + 2; } flag = FALSE; } } fwrite (outbut, sizeof (unsigned short), k, stdout);}fwrite (&eol, sizeof (unsigned short), 1, stdout);fclose(infp);}}______________________________________
|Cited Patent
|Filing date
|Publication date
|Feb 18, 1964
|Apr 23, 1968
|Monsanto Co
|Alkaline earth metal hydroxylapatites, processes for preparing the same and compositions containing the same
|Feb 25, 1974
|Oct 21, 1975
|Miter Inc
|Dental treatments
|Jul 24, 1974
|Sep 6, 1977
|Barsa John J
|Synthesis for crystalline hydroxyapatite
|Jan 19, 1976
|Sep 13, 1977
|Colgate-Palmolive Company
|Dental preparation containing materials having calcium and phosphate components
|Jan 31, 1977
|Jul 4, 1978
|Sterling Drug Inc.
|Hydroxylapatite ceramic
|Jun 2, 1977
|Sep 12, 1978
|Asahi Kogaku Kogyo Kabushiki Kaisha
|Sintered apatite body
|Jan 12, 1976
|Dec 26, 1978
|Ernst Leitz Gmbh
|Bioactive composite material process of producing and method of using same
|Jan 31, 1977
|Jan 23, 1979
|Ernst Leitz Wetzlar Gmbh
|Sintered composite material, a process of making same, and a method of using same
|Nov 10, 1976
|Apr 17, 1979
|Tokyo Medical And Dental University
|Orthopedic and dental implant ceramic composition and process for preparing same
|Dec 21, 1977
|Jun 10, 1980
|Sterling Drug Inc.
|Process for producing polycrystalline ceramic oxides
|May 8, 1978
|Sep 16, 1980
|Kureha Kagaku Kogyo Kabushiki Kaisha
|Composite implant materials and process for preparing same
|Dec 15, 1977
|Sep 23, 1980
|Sumitomo Chemical Company, Limited
|Implants for bones, joints or tooth roots
|Sep 11, 1978
|Sep 23, 1980
|University Of Utah
|Pit and fissure sealant for teeth
|Dec 4, 1978
|Oct 28, 1980
|Asahi Kogaku Kogyo Kabushiki Kaisha
|Prosthetic teeth and bones
|Jun 3, 1980
|Jun 23, 1981
|Tate & Lyle Limited
|Synthetic bone ash
|Jul 23, 1980
|Dec 29, 1981
|Ngk Spark Plugs Co., Ltd.
|Phosphate of calcium ceramics
|Nov 19, 1980
|Apr 13, 1982
|Monsanto Company
|Process for producing hydroxyapatite
|Sep 19, 1980
|May 18, 1982
|Kureha Kagaku Kogyo Kabushiki Kaisha
|Hydroxyapatite, ceramic material and process for preparing thereof
|Aug 9, 1985
|Jun 16, 1987
|Farris Edward T
|Solid calcium phosphate materials
|Jan 21, 1987
|Sep 15, 1987
|Orthomatrix, Inc.
|Ceramic process and products
|Aug 21, 1985
|Oct 13, 1987
|Kuraray Co., Ltd.
|Process for forming calcium phosphate ceramic articles
|Jul 30, 1990
|Dec 31, 1991
|Board Of Regents, The University Of Texas System
|Multiple material systems for selective beam sintering
|Jun 21, 1990
|Jul 21, 1992
|Board Of Regents, The University Of Texas System
|Method for producing parts
|Sep 14, 1989
|Jul 28, 1992
|Asahi Kogaku Kogyo K.K.
|Shaped article of oriented calcium phosphate type compounds, sinter thereof and processes for producing same
|Feb 18, 1992
|Oct 6, 1992
|Olympus Optical Co., Ltd.
|Prosthetic artificial bone having ceramic layers of different porosity
|Apr 26, 1991
|Jan 26, 1993
|Board Of Regents, The University Of Texas System
|Method of producing parts by selective beam interaction of powder with gas phase reactant
|Mar 20, 1992
|Feb 8, 1994
|Board Of Regents, The University Of Texas System
|Method of producing high-temperature parts by way of low-temperature sintering
|Aug 8, 1995
|Feb 22, 1996
|Board Of Regents, The University Of Texas System
|Method and system for fabricating artificial bone implants
|Albee, et al., Ann. Surg ., 71:32 39, 1920.
|Albee, et al., Ann. Surg., 71:32-39, 1920.
|Barlow, 3rd International Conference on Rapid Prototyping , 73 79, 1992.
|Barlow, 3rd International Conference on Rapid Prototyping, 73-79, 1992.
|Bhashar, et al., Oral Surg ., 31:282 289, 1971.
|Bhashar, et al., Oral Surg., 31:282-289, 1971.
|Bovey, et al., Emulsion Polymerization , Interscience Publishers, Inc., 1, 1955.
|Bovey, et al., Emulsion Polymerization, Interscience Publishers, Inc., 1, 1955.
|Cameron, et al., J. Biomed. Materials Res ., 11:179 186, 1977.
|Cameron, et al., J. Biomed. Materials Res., 11:179-186, 1977.
|Corbridge, "Phosphorous: an outline of its chemistry, biochemistry and technology," Elsevier, 224, 1990.
|Corbridge, Phosphorous: an outline of its chemistry, biochemistry and technology, Elsevier, 224, 1990.
|Cutright, et al., Oral Surg ., 33:850 856, 1972.
|Cutright, et al., Oral Surg., 33:850-856, 1972.
|deGroot, J. Biomaterials , 1:47 50, 1980.
|deGroot, J. Biomaterials, 1:47-50, 1980.
|Ferraro, et al., J. Dent. Res ., 58 A:410, 1979.
|Ferraro, et al., J. Dent. Res., 58-A:410, 1979.
|German, Powder Injection Molding , Metal Powder Industrial Federation, 1990.
|German, Powder Injection Molding, Metal Powder Industrial Federation, 1990.
|Hattori, et al., J. Am. Ceram. Soc ., 73(6):1803, 1990.
|Hattori, et al., J. Am. Ceram. Soc., 73(6):1803, 1990.
|Hill, et al., Amer. J. Sci ., 242:457 477, 542 562, 1944.
|Hill, et al., Amer. J. Sci., 242:457-477, 542-562, 1944.
|Holmes, Plast. Rec. Surg ., 63:626 633, 1979.
|Holmes, Plast. Rec. Surg., 63:626-633, 1979.
|Hulbert et al., "History of Bioceramics," Ceramics in Surgery, 3-27, 1983.
|Hulbert et al., History of Bioceramics, Ceramics in Surgery , 3 27, 1983.
|Jarcho, et al., J. Bioeng ., 1:79 92, 1977.
|Jarcho, et al., J. Bioeng., 1:79-92, 1977.
|Jarcho, et al., J. Materials Science , 11:2027 2035, 1976.
|Jarcho, et al., J. Materials Science, 11:2027-2035, 1976.
|Koster, et al., Langenbeck s Arch. Chir ., 341:77 86, 1976.
|Koster, et al., Langenbeck s Arch. Chir ., 343:172 181, 1977.
|Koster, et al., Langenbeck's Arch. Chir., 341:77-86, 1976.
|Koster, et al., Langenbeck's Arch. Chir., 343:172-181, 1977.
|Lee, et al., "Selective Laser Sintering of Bioceramic Materials for Implants," Solid Freeform Fabrication Proceedings, 376-380, 1993.
|Lee, et al., Selective Laser Sintering of Bioceramic Materials for Implants, Solid Freeform Fabrication Proceedings , 376 380, 1993.
|Lefebvre, Atomization and Sprays , Hemisphere Publishing, 1989.
|Lefebvre, Atomization and Sprays, Hemisphere Publishing, 1989.
|Levy, et al., Am J. Of Neuroradiology , 15:473 477, 1994.
|Levy, et al., Am J. Of Neuroradiology, 15:473-477, 1994.
|Levy, et al., Solid Freeform Fabrication Symposium Proceedings , 3:161 173, 1992.
|Levy, et al., Solid Freeform Fabrication Symposium Proceedings, 3:161-173, 1992.
|McIntosh, et al., Anal. Chem ., 28(9):1424 1427, 1956.
|McIntosh, et al., Anal. Chem., 28(9):1424-1427, 1956.
|Nelson, et al., J. Oral & Maxillofacial Surg ., 51:1363 1371, 1993.
|Nelson, et al., J. Oral & Maxillofacial Surg., 51:1363-1371, 1993.
|Nielson, Acta Chir. Scandanav ., 91:17 27, 1944.
|Nielson, Acta Chir. Scandanav., 91:17-27, 1944.
|PCT Search Report US95/10017 issued Dec. 20, 1995.
|Peltier, et al., Ann. Surg ., 146:61 64, 1957.
|Peltier, et al., Ann. Surg., 146:61-64, 1957.
|Vail, et al., "Development of a Poly(Methyl Methacrylate-co-n-Butyl Methacrylate) Copolymer Binder System," J. Appl. Polym. Sci., 52:789-812, 1994.
|Vail, et al., "Silicon Carbide Preforms for Metal Infiltration by Selective Laser Sintering™ of Polymer Encapsulated Powders," Solid Freeform Fabrication Proceeding, 204-214, 1993.
|Vail, et al., Development of a Poly(Methyl Methacrylate co n Butyl Methacrylate) Copolymer Binder System, J. Appl. Polym. Sci ., 52:789 812, 1994.
|Vail, et al., Silicon Carbide Preforms for Metal Infiltration by Selective Laser Sintering of Polymer Encapsulated Powders, Solid Freeform Fabrication Proceeding , 204 214, 1993.
|Vail, et al., Solid Freeform Fabrication Symposium Proceedings , 2:195 205, 1991.
|Vail, et al., Solid Freeform Fabrication Symposium Proceedings , 3:124 130, 1992.
|Vail, et al., Solid Freeform Fabrication Symposium Proceedings, 2:195-205, 1991.
|Vail, et al., Solid Freeform Fabrication Symposium Proceedings, 3:124-130, 1992.
|Van Wazer, "Phosphorous and Its Compounds," Interscience Publisher, 1, 517-522, 1958.
|Van Wazer, Phosphorous and Its Compounds , Interscience Publisher, 1, 517 522, 1958.
|Yoshihiro, Shika Rikogaku Zasshi , 16:196 202, 1975.
|Yoshihiro, Shika Rikogaku Zasshi, 16:196-202, 1975.
|Citing Patent
|Filing date
|Publication date
|Jul 24, 1995
|Feb 16, 1999
|Julie Cougoulic
|Method for preparing a material for medical or veterinary use, resulting material, and uses thereof
|Aug 15, 1997
|Mar 30, 1999
|Gibbs; David
|Dental implant
|Sep 4, 1996
|May 11, 1999
|Z Corporation
|Method of three dimensional printing
|Sep 18, 1998
|Feb 8, 2000
|Johnson & Johnson Professional, Inc.
|Precision powder injection molded implant with preferentially leached texture surface and method of manufacture
|May 15, 1997
|Jun 20, 2000
|Kandel; Rita
|Resorbable implant biomaterial made of condensed calcium phosphate particles
|Dec 19, 1997
|Jul 25, 2000
|Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno
|Method for manufacturing a fiber-reinforced bioactive ceramic implant
|Apr 4, 1997
|Feb 6, 2001
|Board Of Regents, The University Of Texas System
|Artificial bone implants
|Jun 12, 2000
|May 15, 2001
|University Of Utah Research Foundation
|Rapid prototyping method
|Sep 22, 1999
|Jun 19, 2001
|Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Ondersoek Tno
|Method for manufacturing a fiber-reinforced bioactive ceramic implant
|Nov 24, 1998
|Jun 26, 2001
|David Gibbs
|Resorbable implant
|Jun 5, 2000
|Aug 7, 2001
|Rensselaer Polytechnic Institute
|Nanostructured ceramics and composite materials for orthopaedic-dental implants
|Jan 29, 1999
|Jul 9, 2002
|Z Corporation
|Three dimensional printing materials system
|Jan 19, 2001
|Apr 1, 2003
|Board Of Regents, The University Of Texas System
|Artificial bone implants
|Apr 10, 2001
|Aug 26, 2003
|Z Corporation
|Three dimensional printing material system and method
|May 29, 2002
|Nov 23, 2004
|The Boeing Company
|Thermocouple control system for selective laser sintering part bed temperature control
|Nov 15, 1999
|Dec 20, 2005
|Wright Medical Technology Inc.
|Process for producing rigid reticulated articles
|Sep 23, 2001
|Feb 28, 2006
|Ingo Ederer
|Device for manufacturing models layer by layer
|Sep 25, 2002
|Aug 8, 2006
|Z Corporation
|Three dimensional printing material system and method
|Aug 26, 2002
|Sep 26, 2006
|Pentax Corporation
|Implant forming method
|Apr 12, 2002
|Oct 17, 2006
|Therics, Llc
|Method and apparatus for engineered regenerative biostructures such as hydroxyapatite substrates for bone healing applications
|Dec 28, 2005
|Nov 21, 2006
|Ingo Ederer
|Device for pattern building in layers
|Nov 26, 1997
|Dec 12, 2006
|Bernard Francis Grisoni
|Monolithic implants with openings
|Sep 23, 2001
|Apr 17, 2007
|Ingo Ederer
|Interchangeable container
|Oct 22, 2004
|Jul 31, 2007
|Wright Medical Technology, Inc.
|Synthetic bone substitute material
|Feb 22, 2006
|Mar 11, 2008
|Chemat Technology, Inc.
|Coated implants and methods of coating
|Jun 15, 2005
|Oct 14, 2008
|Hewlett-Packard Development Company, L.P.
|Cement system including a binder for use in freeform fabrication
|Oct 10, 2002
|Mar 24, 2009
|The Regents Of The University Of Michigan
|Solid freeform fabrication of structurally engineered multifunctional devices
|May 20, 2003
|May 12, 2009
|Ingo Ederer
|Method for constructing patterns in a layered manner
|Sep 10, 2004
|Dec 22, 2009
|Honda Giken Kogyo Kabushiki Kaisha
|Method of producing composite material
|Mar 6, 2008
|Jan 19, 2010
|Chemat Technology, Inc.
|Coated implants and methods of coating
|Jun 25, 2007
|Jun 15, 2010
|Ingo Ederer
|Method for the construction of a laminated compound
|Oct 6, 2005
|Jun 22, 2010
|Wright Medical Technology, Inc.
|Process for producing rigid reticulated articles
|Apr 8, 2003
|Jul 6, 2010
|Voxeljet Technology Gmbh
|Method and device for applying fluids
|Sep 8, 2006
|Jul 13, 2010
|Wright Medical Technology, Inc.
|Composite bone graft substitute cement and articles produced therefrom
|Jul 2, 2007
|Aug 3, 2010
|Wright Medical Technology, Inc.
|Synthetic, malleable bone graft substitute material
|May 24, 2005
|Aug 3, 2010
|Voxeljet Technology Gmbh
|Method and device for production of a three-dimensional article
|Nov 13, 2006
|Aug 10, 2010
|Biomet 3l, LLC
|Deposition of discrete nanoparticles on an implant surface
|May 24, 2006
|Sep 14, 2010
|Z Corporation
|Material systems and methods of three-dimensional printing
|Jun 11, 2004
|Oct 5, 2010
|Voxeljet Technology Gmbh
|Methods and systems for the manufacture of layered three-dimensional forms
|May 12, 2005
|Oct 19, 2010
|Massachusetts Institute Of Technology
|Manufacturing process, such as three-dimensional printing, including solvent vapor filming and the like
|Mar 26, 2002
|Feb 1, 2011
|Ingo Ederer
|Method and device for applying fluids
|Dec 7, 2007
|Mar 15, 2011
|Z Corporation
|Three dimensional printing material system and method using peroxide cure
|Jun 9, 2010
|Apr 19, 2011
|Ingo Ederer
|Method for the construction of a laminated compound
|Jul 7, 2009
|Jun 7, 2011
|Ingo Ederer
|Method for constructing patterns in a layered manner
|Feb 22, 2008
|Jun 28, 2011
|Z Corporation
|Three dimensional printing material system and method using plasticizer-assisted sintering
|Jul 31, 2008
|Jul 19, 2011
|Errcive, Inc.
|Porous bodies and methods
|Jun 9, 2005
|Sep 6, 2011
|Synthes Usa, Llc
|Flexible bone composite
|Jun 14, 2004
|Sep 20, 2011
|Hoechsmann Rainer
|Method for the layered construction of models
|Feb 13, 2007
|Sep 27, 2011
|Wright Medical Technology, Inc.
|Composite bone graft substitute cement and articles produced therefrom
|Jun 3, 2011
|Jan 10, 2012
|Errcive, Inc.
|Porous bodies and methods
|Feb 11, 2005
|Jan 17, 2012
|Ingo Ederer
|Method and device for applying fluids
|Jun 3, 2011
|Jan 17, 2012
|Errcive, Inc.
|Porous bodies and methods
|Aug 18, 2011
|Feb 28, 2012
|Rainer Hochsmann
|Method for the layered construction of models
|Jan 28, 2011
|Apr 17, 2012
|3D Systems, Inc.
|Three dimensional printing material system and method using peroxide cure
|Jan 10, 2008
|May 1, 2012
|3D Systems, Inc.
|Three-dimensional printing material system with improved color, article performance, and ease of use
|Dec 11, 2011
|Jul 17, 2012
|Errcive, Inc.
|Porous bodies and methods
|Apr 8, 2010
|Oct 2, 2012
|Errcive, Inc.
|Substrate fabrication
|Jan 26, 2009
|Nov 13, 2012
|Biomet 3I, Llc
|Implant surface with increased hydrophilicity
|Jul 31, 2009
|Dec 4, 2012
|United States Gypsum Company
|Method for preparing three-dimensional plaster objects
|Oct 1, 2008
|Jan 8, 2013
|Voxeljet Gmbh
|Material system and method for changing properties of a plastic component
|Jun 25, 2010
|Jan 29, 2013
|Ramberg Charles E
|Powertrain controls
|Jun 12, 2012
|Jan 29, 2013
|Errcive, Inc.
|Porous bodies and methods
|Jul 31, 2008
|Jan 29, 2013
|Errcive, Inc.
|Porous bodies and methods
|Jul 2, 2012
|Apr 16, 2013
|Synthes Usa, Llc
|Flexible bone composite
|Mar 20, 2007
|Jul 2, 2013
|Bowling Green State University
|Ceramic article and method of manufacture
|Nov 5, 2010
|Jul 9, 2013
|Ormco Corporation
|Method of manufacturing an orthodontic bracket having a laser shaped green body
|Nov 13, 2006
|Jul 16, 2013
|Biomet 3I, Llc
|Deposition of discrete nanoparticles on an implant surface
|Feb 2, 2011
|Aug 13, 2013
|3D Systems, Inc.
|Three dimensional printing material system and method using plasticizer-assisted sintering
|Jun 10, 2008
|Aug 13, 2013
|Voxeljet Technology Gmbh
|Methods of manufacturing layered three-dimensional forms
|Feb 3, 2010
|Oct 8, 2013
|Errcive, Inc.
|Porous bodies and methods
|Mar 20, 2007
|Oct 29, 2013
|Bowling Green State University
|Three-dimensional printer, ceramic article and method of manufacture
|Apr 2, 2003
|Dec 10, 2013
|DePuy Synthes Products, LLC
|Kneadable and pliable bone replacement material
|Nov 15, 2011
|Dec 24, 2013
|Zimmer Orthobiologics, Inc.
|Bone void fillers
|Dec 15, 2011
|Jan 7, 2014
|Errcive, Inc.
|Porous bodies and methods
|Mar 29, 2011
|Feb 4, 2014
|Biomet 3I, Llc
|Titanium nano-scale etching on an implant surface
|Dec 13, 2007
|Mar 4, 2014
|Said G. Osman
|Biologic artificial bone
|Aug 24, 2012
|Mar 25, 2014
|Errcive, Inc.
|Substrate fabrication
|Jan 18, 2007
|Apr 1, 2014
|Agnovos Healthcare, Llc
|Composite bone graft substitute cement and articles produced therefrom
|Aug 29, 2011
|Apr 1, 2014
|Agnovos Healthcare, Llc
|Composite bone graft substitute cement and articles produced therefrom
|Aug 3, 2010
|Apr 8, 2014
|Zimmer Orthobiologics, Inc.
|Composition and process for bone growth and repair
|Nov 2, 2009
|May 6, 2014
|Voxeljet Ag
|Method for the layered construction of plastic models
|Oct 6, 2008
|May 20, 2014
|Voxeljet Ag
|Method and device for conveying particulate material during the layer-wise production of patterns
|Sep 25, 2000
|Jun 3, 2014
|Voxeljet Ag
|Method for producing a part using a depostion technique
|Mar 29, 2010
|Jun 3, 2014
|Zimmer Orthobiologics, Inc.
|Bone growth particles and osteoinductive composition thereof
|Mar 15, 2013
|Jul 8, 2014
|DePuy Synthes Products, LLC
|Flexible bone composite
|Dec 25, 2012
|Sep 2, 2014
|Errcive, Inc.
|Porous bodies and methods
|Jul 20, 2012
|Sep 23, 2014
|Biomet Manufacturing, Llc
|Metallic structures having porous regions from imaged bone at pre-defined anatomic locations
|Aug 7, 2013
|Sep 30, 2014
|Tethon Corporation
|Three-dimensional printer, ceramic article and method of manufacture
|Oct 10, 2012
|Oct 7, 2014
|Biomet 3I, Llc
|Implant surface with increased hydrophilicity
|Mar 5, 2009
|Oct 28, 2014
|Ormco Corporation
|Methods for shaping green bodies and articles made by such methods
|Apr 11, 2011
|Dec 16, 2014
|Voxeljet Ag
|Device for producing three-dimensional models
|Jul 8, 2013
|Jan 13, 2015
|Ormco Corporation
|Method of manufacturing an orthodontic bracket having a laser shaped green body
|Jul 10, 2011
|Feb 17, 2015
|Voxeljet Ag
|Apparatus for producing three-dimensional models by means of a layer build up technique
|Feb 1, 2011
|Feb 17, 2015
|Voxeijet AG
|Device for producing three-demensional models
|Oct 6, 2008
|Mar 31, 2015
|Voxeijet AG
|Device for the layer-wise production of patterns
|Oct 9, 2013
|May 19, 2015
|Biomet 3I, Llc
|Titanium nano-scale etching on an implant surface
|Dec 9, 2013
|Jun 9, 2015
|DePuy Synthes Products, LLC
|Kneadable and pliable bone replacement material
|Dec 17, 2014
|Aug 18, 2015
|Ormco Corporation
|Method of manufacturing an orthodontic bracket having a laser shaped green body
|Mar 11, 2013
|Sep 15, 2015
|Biomet 3I, Llc
|Surface treatment for an implant surface
|Nov 19, 2014
|Oct 6, 2015
|Voxeljet Ag
|Device for producing three-dimensional models by a layering technique
|Dec 28, 2010
|Nov 3, 2015
|DePuy Synthes Products, Inc.
|Integrated multi-material implants and methods of manufacture
|Mar 28, 2011
|Nov 3, 2015
|Voxeljet Ag
|Device for producing three-dimensional models
|Jun 18, 2010
|Nov 3, 2015
|Voxeljet Ag
|Method and device for switching a particulate material flow in the construction of models in layers
|Jun 11, 2010
|Nov 10, 2015
|Agnovos Healthcare, Llc
|Composite bone graft substitute cement and articles produced therefrom
|Aug 27, 2014
|Dec 1, 2015
|Biomet 3I, Llc
|Implant surface with increased hydrophilicity
|Mar 30, 2006
|Dec 8, 2015
|The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc.
|Light as a replacement for mitogenic factors on progenitor cells
|Oct 14, 2011
|Jan 26, 2016
|Voxeljet Ag
|Device and method for constructing a laminar body comprising at least one position adjustable body defining the working area
|Apr 15, 2015
|Mar 15, 2016
|Biomet 3I, Llc
|Titanium nano-scale etching on an implant surface
|Jan 21, 2014
|May 3, 2016
|Amendia, Inc.
|Biologic artificial bone
|Mar 29, 2011
|May 10, 2016
|Voxeljet Ag
|Device and method for producing three-dimensional models
|Jun 2, 2014
|Aug 2, 2016
|Voxeljet Ag
|Method for producing a part using a deposition technique
|Dec 12, 2014
|Sep 20, 2016
|Agnovos Healthcare, Llc
|Multiphasic bone graft substitute material
|Dec 16, 2011
|Oct 11, 2016
|Voxeljet Ag
|Method for applying particle material including a metering system and leveling element
|Apr 11, 2014
|Oct 18, 2016
|Voxeljet Ag
|Method and device for conveying particulate material during the layer-wise production of patterns
|Jul 1, 2008
|Nov 29, 2016
|Voxeljet Ag
|Method for producing three-dimensional components
|Mar 20, 2014
|Dec 6, 2016
|Errcive, Inc.
|Substrate fabrication
|Sep 24, 2014
|Jan 10, 2017
|Ormco Corporation
|Methods for shaping green bodies and articles made by such methods
|Aug 6, 2007
|May 9, 2017
|Voxeljet Ag
|Self-hardening material and process for layerwise formation of models
|Dec 21, 2015
|May 16, 2017
|Voxeljet Ag
|Device and method for constructing a laminar body comprising at least one position-adjustable body defining the working area
|Nov 2, 2015
|May 23, 2017
|Voxeljet Ag
|Device and method for producing three-dimensional models
|Aug 19, 2010
|Jun 6, 2017
|Smith & Nephew, Inc.
|Porous implant structures
|Aug 2, 2013
|Jun 13, 2017
|Voxeljet Ag
|Self-hardening material and process for layerwise formation of models
|Mar 10, 2016
|Sep 12, 2017
|Biomet 3I, Llc
|Titanium nano-scale etching on an implant surface
|Feb 27, 2015
|Sep 12, 2017
|Voxeljet Ag
|Methods for assembling a device for the layer-wise production of patterns
|Jul 3, 2013
|Sep 19, 2017
|Biomet 3I, Llc
|Deposition of discrete nanoparticles on an implant surface
|Mar 17, 2016
|Sep 26, 2017
|Voxeljet Ag
|Method and material system for building models in layers
|Apr 16, 2002
|Nov 14, 2002
|Cerabio, L.L.C.
|Dense porous structures for use as bone substitutes
|Aug 26, 2002
|Mar 6, 2003
|Asahi Kogaku Kogyo Kabushiki Kaisha
|Implant forming method
|Apr 12, 2002
|Apr 3, 2003
|Beam Heather Ann
|Method and apparatus for engineered regenrative biostructures such as hydroxyapatite substrates for bone healing applications
|Oct 10, 2002
|Apr 17, 2003
|Suman Das
|Solid freeform fabrication of structurally engineered multifunctional devices
|Oct 4, 2001
|Feb 12, 2004
|Ingo Ederer
|Method for unpacking shaped bodies embedded inside unbound particle material
|Sep 23, 2001
|Feb 12, 2004
|Ingo Ederer
|Interchangeable container
|Sep 23, 2001
|Feb 26, 2004
|Ingo Ederer
|Device for manufacturing models layer by layer
|Sep 25, 2002
|Mar 25, 2004
|Bredt James F.
|Three dimensional printing material system and method
|Mar 26, 2002
|Sep 2, 2004
|Ingo Ederer
|Method and device for applying fluids
|Jun 11, 2004
|Jan 27, 2005
|Voxeljet Gmbh
|Methods and systems for the manufacture of layered three-dimensional forms
|Sep 10, 2004
|Mar 10, 2005
|Honda Giken Kogyo Kabushiki Kaisha
|Method of producing composite material
|Aug 25, 2004
|Mar 17, 2005
|Z Corporation
|Absorbent fillers for three-dimensional printing
|Oct 18, 2004
|Apr 21, 2005
|Shappley Ben R.
|Shaped filler for implantation into a bone void and methods of manufacture and use thereof
|Apr 2, 2003
|Jun 9, 2005
|Mathys Medizinaltechnik Ag
|Kneadable and pliable bone replacement material
|May 20, 2003
|Aug 4, 2005
|Tatsuo Tsubaki
|Method for constructing patterns in a layered manner
|Oct 18, 2004
|Aug 11, 2005
|Ben Shappley
|Spinal cage insert, filler piece and method of manufacturing
|Feb 28, 2005
|Sep 8, 2005
|Z Corporation
|Compositions for three-dimensional printing of solid objects
|Jun 15, 2005
|Oct 20, 2005
|Christopher Oriakhi
|Cement system including a binder for use in freeform fabrication
|Jun 9, 2005
|Jan 12, 2006
|Sean Kerr
|Flexible bone composite
|Oct 22, 2004
|Apr 27, 2006
|Wright Medical Technology, Inc.
|Synthetic bone substitute material
|Oct 6, 2005
|May 4, 2006
|Marx Jeffrey G
|Process for producing rigid reticulated articles
|Apr 8, 2003
|May 18, 2006
|Rainer Hochsmann
|Method and device for applying fluids
|Dec 28, 2005
|May 25, 2006
|Ingo Ederer
|Device for pattern building in layers
|Feb 22, 2006
|Jun 29, 2006
|Jiankai Liu
|Coated implants and methods of coating
|Jul 29, 2005
|Jul 27, 2006
|Norbert Abels
|Methods for shaping green bodies and articles made by such methods
|Jul 29, 2005
|Jul 27, 2006
|Norbert Abels
|Laser shaping of green metal body used in manufacturing an orthodontic bracket
|Jun 14, 2004
|Oct 26, 2006
|Voxelet Gmbh
|Method for the layered construction of models
|May 15, 2006
|Nov 2, 2006
|Thorne Kevin J
|Composition and Process for Bone Growth and Repair
|May 12, 2005
|Jan 11, 2007
|Serdy James G
|Manufacturing process, such as three dimensional printing, including binding of water-soluble material followed by softening and flowing and forming films of organic-solvent-soluble material
|Nov 13, 2006
|May 17, 2007
|Berckmans Bruce Iii
|Deposition of discrete nanoparticles on an implant surface
|Nov 13, 2006
|May 17, 2007
|Berckmans Bruce Iii
|Deposition of discrete nanoparticles on an implant surface
|Apr 28, 2005
|Oct 4, 2007
|Kunio Nishimoto
|Biocompatible Membrane and Process for Producing the Same
|Jul 2, 2007
|Jan 17, 2008
|Wright Medical Technology, Inc.
|Synthetic Bone Substitute Material
|May 12, 2005
|Feb 7, 2008
|Massachusetts Institute Of Technology
|Manufacturing Process, Such as Three-Dimensional Printing, Including Solvent Vapor Filming and the Like
|Mar 6, 2008
|Jun 26, 2008
|Jiankai Liu
|Coated implants and methods of coating
|May 24, 2005
|Sep 25, 2008
|Technische Universit�t Berlin
|Method and Device for Production of a Three-Dimensional Article
|Jun 10, 2008
|Oct 2, 2008
|Rainer Hochsmann
|Methods and systems for manufacturing the manufacture of layered three-dimensional forms
|Dec 13, 2007
|Jun 18, 2009
|Osman Said G
|Biologic Artificial Bone
|Mar 5, 2009
|Jul 2, 2009
|Ormco Corporation
|Methods for shaping green bodies and articles made by such methods
|Jan 26, 2009
|Jul 30, 2009
|Biomet 3I, Llc
|Implant surface with increased hydrophilicity
|Oct 13, 2009
|Feb 4, 2010
|Bego Bremer Goldschlagerei Wilh. Herbst Gmbh & Co. Kg
|Method for Producing Tooth Replacements and Auxiliary Dental Parts
|Feb 3, 2010
|Jun 3, 2010
|Ramberg Charles E
|Porous Bodies and Methods
|Oct 6, 2008
|Aug 26, 2010
|Voxeljet Technology Gmbh
|Device for the layer-wise production of patterns
|Jun 9, 2010
|Sep 30, 2010
|Voxeljet Technology Gmbh
|Method for the construction of a laminated compound
|Oct 1, 2008
|Sep 30, 2010
|Voxeljet Technology Gmbh
|Material system and method for changing properties of a plastic component
|Oct 6, 2008
|Oct 28, 2010
|Voxeljet Technology Gmbh
|Method and device for conveying particulate material during the layer-wise production of patterns
|Aug 6, 2007
|Nov 18, 2010
|Voxeljet Technology
|Self-hardening material and process for layerwise formation of models
|Jul 31, 2009
|Feb 3, 2011
|United States Gypsum Company
|Method for preparing three-dimensional plaster objects
|Nov 5, 2010
|Mar 3, 2011
|Ormco Corporation
|Laser shaped green metal body and orthodontic bracket
|Dec 28, 2010
|Aug 4, 2011
|Beat Lechmann
|Integrated multi-material implants and methods of manufacture
|Nov 2, 2009
|Sep 15, 2011
|Voxeljet Technology Gmbh
|Method for the layered construction of plastic models
|Jul 2, 2012
|Oct 25, 2012
|Synthes Usa, Llc
|Flexible Bone Composite
|Apr 8, 2013
|Apr 30, 2015
|Limacorporate Spa
|Prosthetic Element for Bone Extremities Such as Fingers or Toes, or for Teeth, and Corresponding Production Method
|Sep 24, 2014
|May 21, 2015
|Ormco Corporation
|Methods for shaping green bodies and articles made by such methods
|Feb 16, 2016
|Jun 9, 2016
|Ormco Corporation
|Methods for shaping green bodies and articles made by such methods
|Dec 18, 2003
|Nov 21, 2007
|Hewlett-Packard Development Company, L.P.
|A cement system including a binder for use in freeform fabrication
|Jul 1, 1998
|Jan 14, 1999
|University Of Utah Research Foundation
|Improved rapid prototyping method
|Jul 1, 1998
|Mar 25, 1999
|Univ Utah Res Found
|Improved rapid prototyping method
|Nov 12, 2010
|Sep 29, 2011
|Smith & Nephew, Inc.
|Controlled randomized porous structures and methods for making same
|Dec 28, 2010
|Jul 7, 2011
|Synthes Usa, Llc
|Intergrated multi-material implants and methods of manufacture
|Jan 9, 2015
|Jul 16, 2015
|United Technologies Corporation
|Material and processes for additively manufacturing one or more parts
|U.S. Classification
|264/6, 264/482, 264/430, 264/497, 264/434
|International Classification
|Cooperative Classification
|European Classification
|Oct 24, 1994
Owner name: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM,
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BARLOW, JOEL W.;LEE, GOONHEE;CRAWFORD, RICHARD H.;AND OTHERS;REEL/FRAME:007173/0915
Effective date: 19941006
|Jul 31, 1997
Owner name: NAVY, SECRETARY OF THE, UNITED STATES OF AMERICA,
Free format text: CONFIRMATORY INSTRUMENT;ASSIGNOR:TEXAS, UNIVERSITY OF, AT AUSTIN;REEL/FRAME:008626/0980
Effective date: 19950824
|Nov 21, 2000
|Fee payment
Year of fee payment: 4
|Dec 14, 2004
|Fee payment
Year of fee payment: 8
|Dec 5, 2008
|Fee payment
Year of fee payment: 12
|Apr 6, 2009
Owner name: CROSS ATLANTIC PARTNERS IV, K/S, AS ADMINISTRATIVE
Free format text: SECURITY AGREEMENT;ASSIGNOR:BIOMEDICAL ENTERPRISES, INC.;REEL/FRAME:022510/0127
Effective date: 20090406
|Jun 2, 2009
Owner name: CROSS ATLANTIC PARTNERS IV, K/S AS ADMINISTRATIVE
Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:BIOMEDICAL ENTERPRISES, INC.;REEL/FRAME:022764/0679
Effective date: 20090406
|Jun 5, 2009
Owner name: BIOMEDICAL ENTERPRISES, INC., TEXAS
Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE IDENTITY OF THE ASSIGNOR AND THE ASSIGNEE. PREVIOUSLY RECORDEDON REEL 022764 FRAME 0679;ASSIGNOR:CROSS ATLANTIC PARTNERS IV, K/S;REEL/FRAME:022783/0734
Effective date: 20090602


text:
We know what you're thinking: Is Mott Haven really worth the trek out to the Bronx? The answer is a simple, and colorful, yes.
The neighborhood, located in the South Bronx, is home to numerous historical churches, authentic eats and vibrant street art.
If you're coming from midtown, you'll want to hop on the 6 train to get to Mott Haven in just under one hour.
Here's how to spend the day in the area.
Enjoy breakfast at Nick's Blue Diner
Repair your soul (and sole) at Shoe Repair & Botanica
On Sundays, opt for brunch at Charlies Bar & Kitchen
Admire St. Jerome's Church
Walk the historic Bertine Block
Search for the secret passageway at St. Ann's
Go for a stroll through the park
Dine at Mott Haven's Mexican jewels

subset: commoncrawl