Claims
- 1. A method of producing a bone-polymer composite, comprising:
providing a plurality of bone particles; combining the bone particles with a precursor of a biocompatible polymer; and polymerizing the polymer precursor.
- 2. The method of claim 1, wherein polymerizing the polymer precursor comprises one or more of cross-linking the polymer precursor, increasing the molecular weight of the polymer precursor, and creating covalent bonds linking the polymerized polymer precursor with the bone particles.
- 3. The method of claim 1, wherein the polymer precursor is selected from a monomer, a prepolymer, a flowable polymer, and a partially polymerized polymer.
- 4. The method of claim 1, further comprising infiltrating the polymer precursor into the vascular and interstitial structures of the bone particles.
- 5. The method of claim 1, wherein the bone particles are selected from the group consisting of nondemineralized bone particles, demineralized bone particles, and mixtures thereof.
- 6. The method of claim 1, wherein the bone particles are obtained from a member of the group consisting of cortical bone, cancellous bone, cortico-cancellous bone, and mixtures thereof.
- 7. The method of claim 1, wherein the bone particles are obtained from a member of the group consisting of autogenous bone, allogenic bone, xenogeneic bone, and mixtures thereof.
- 8. The method of claim 1, wherein the bone particles are about 1% to about 25% by weight of the composite.
- 9. The method of claim 1, wherein the bone particles are about 26% to about 50% by weight of the composite.
- 10. The method of claim 1, wherein the bone particles are about 51% to about 75% by weight of the composite.
- 11. The method of claim 1, wherein the bone particles are about 76% to about 99% by weight of the composite.
- 12. The method of claim 1, wherein at least about 60% of the bone particles are elongate.
- 13. The method of claim 1, further comprising modifying a surface of the bone particles.
- 14. The method of claim 13, wherein modifying a surface comprises attaching a silane coupling agent to the bone particles, wherein the silane coupling agent comprises an active group that is incorporated into the polymerized polymer precursor.
- 15. The method of claim 14, wherein the active group is monofunctional or multifunctional.
- 16. The method of claim 13, wherein the step of modifying comprises attaching a attaching a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic material, a mineral, and any combination of the above to the bone particles.
- 17. The method of claim 13, wherein modifying a surface comprises attaching a silane coupling agent to the bone particles and attaching a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic material, a mineral, and any combination of the above to the silane coupling agent.
- 18. The method of claim 17, wherein the silane coupling agent includes a non-biocompatible leaving group.
- 19. The method of claim 16 or 17, wherein the moiety is incorporated into the polymerized polymer precursor or linked to the polymerized polymer precursor by a member of covalent and non-covalent interactions.
- 20. The method of claim 13, wherein modifying the surface comprises exposing collagen fibers at the surface of the bone particles.
- 21. The method of claim 20, further comprising fraying the exposed collagen fibers.
- 22. The method of claim 20, further comprising cross-linking the exposed collagen fibers.
- 23. The method of claim 20, further comprising derivatizing the exposed collagen fibers with a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic material, a mineral, and any combination of the above.
- 24. The method of claim 13, wherein modifying a surface comprises washing the bone particles in phosphoric acid.
- 25. The method of claim 1, wherein the polymerized polymer precursor is a polymer selected from the group consisting of biodegradable, non-biodegradable, co-polymers of biodegradable polymers, co-polymers of non-biodegradable polymers, and co-polymers of biodegradable and non-biodegradable polymers.
- 26. The method of claim 1, wherein the monomer or prepolymer forms a polymer selected from the group consisting of poly(phosphoesters), polysulfones, polyfumarates, polyphosphazines, poly(alkylene oxides), poly(arylates), poly(anhydrides), poly(hydroxy acids), polyesters, poly(ortho esters), polycarbonates, poly(propylene fumerates), poly(caprolactones), polyamides, polyamino acids, polyacetals, polylactides, polyglycolides, poly(dioxanones), polyhydroxybutyrate, polyhydroxyvalyrate, poly(vinyl pyrrolidone), biodegradable polycyanoacrylates, biodegradable polyurethanes, polysaccharides, tyrosine-based polymers, poly(pyrrole), poly(aniline), poly(thiophene), polystyrene, non-biodegradable polyurethanes, polyureas, poly(ethylene vinyl acetate), polypropylene, polymethacrylate, polyethylene, poly(ethylene oxide), and mixtures, adducts, and co-polymers thereof.
- 27. The method of claim 1, further comprising placing the bone particle/polymer precursor mixture in a mold before polymerization.
- 28. The method of claim 1, further comprising:
partially polymerizing the polymer precursor; charging a mold with the partially polymerized material; and completing polymerization to form the bone-polymer composite.
- 29. The method of claim 1, further comprising shaping the bone particle/polymer precursor mixture in a shape selected from the group consisting of a bone, a section of a bone, sheet, plate, particle, sphere, strand, coiled strand, capillary network, film, fiber, mesh, disk, cone, pin, screw, tube, cup, tooth, tooth root, strut, wedge, portion of wedge, cylinder, threaded cylinder, and rod.
- 30. The method of claim 1, further comprising partially polymerizing the polymer precursor, putting the partially polymerized mixture in an implant site and completing polymerization.
- 31. The method of claim 1, further comprising putting the polymer precursor-particle mixture in an implant site before polymerization.
- 32. The method of claim 1, further comprising modifying a surface of the composite after polymerization.
- 33. The method of claim 32, wherein the step of modifying a surface comprises a member of the group consisting of oxidizing at least a portion of the surface, roughening at least a portion of the surface, etching at least a portion of the surface, retaining a biomolecule on the surface, retaining a small molecule on the surface, retaining a bioactive agent on the surface, retaining an inorganic material on the surface, retaining a mineral on the surface, and any combination of the above.
- 34. The method of claim 1, further comprising machining the composite into a shape following the step of polymerization.
- 35. The method of claim 34, wherein the shape is selected from the group consisting of a bone, a section of a bone, sheet, particle, sphere, strand, coiled strand, capillary network, film, fiber, mesh, plate, disk, cone, pin, screw, tube, cup, tooth, tooth root, strut, wedge, portion of wedge, cylinder, threaded cylinder, and rod.
- 36. The method of claim 34, further comprising fastening a plurality of machined pieces of composite together.
- 37. The method of claim 36, wherein the machined pieces are fastened together with a member of an adhesive, a mechanical fastener, ultrasonic bonding, and any combination of the above.
- 38. The method of claim 1, further comprising machining the composite into particles after polymerization and compressing the particles to form an osteoimplant.
- 39. The method of claim 38, wherein the composite particles are compressed with a force greater than about 1000 psi.
- 40. The method of claim 38, wherein the composite particles are compressed with a force between about 2500 and about 60,000 psi.
- 41. The method of claim 38, wherein the compressed composite particles have a void volume not greater than 32%.
- 42. The method of claim 38, further comprising combining the composite particles with a member of a wetting agent, biocompatible binder, filler, fiber, plasticizer, biostatic/biocidal agent, surface active agent, biomolecule, small molecule, bioactive agent, and any combination of the above before compressing.
- 43. The method of claim 38, wherein the compressed composite particles have a shape selected from the group consisting of a bone, a section of a bone, sheet, plate, particle, sphere, strand, coiled strand, capillary network, film, fiber, mesh, disk, cone, pin, screw, tube, cup, tooth, tooth root, strut, wedge, portion of wedge, cylinder, threaded cylinder, and rod.
- 44. The method of claim 1, further comprising machining the composite into particles and wet-laying the particles to form an osteoimplant.
- 45. The method of claim 1, further comprising heating at least a portion of the composite to a temperature at which the polymer flows.
- 46. The method of claim 45, further comprising implanting the at least partially melted composite into an implant site before allowing the composite to cool.
- 47. The method of claim 1, further comprising compressing the plurality of bone particles together in a predetermined shape after combining them with the polymer precursor.
- 48. The method of claim 47, wherein the compressed bone particles have a void volume not greater than 32%.
- 49. The method of claim 47, further comprising combining the bone particles with a member of a wetting agent, biocompatible binder, filler, fiber, plasticizer, biostatic/biocidal agent, surface active agent, biomolecule, small molecule, bioactive agent, and any combination of the above before compressing.
- 50. The method of claim 47, wherein the compressed bone particles have a shape selected from the group consisting of a bone, a section of a bone, sheet, plate, particle, sphere, strand, coiled strand, capillary network, film, fiber, mesh, disk, cone, pin, screw, tube, cup, tooth, tooth root, strut, wedge, portion of wedge, cylinder, threaded cylinder, and rod.
- 51. A composition, comprising:
a plurality of bone particles; and a polymer precursor selected from a monomer, a prepolymer, a flowable biocompatible polymer, and a partially-polymerized biocompatible polymer, wherein: the composition is adapted and constructed such that, when the polymer precursor is polymerized, at least a portion of the bone particles are covalently attached to the polymerized polymer precursor, at least a portion of the interstitial and vascular structure of the bone particles is infiltrated by the polymerized polymer precursor, or both.
- 52. The composition of claim 51, wherein at least a portion of the bone particles are covalently linked to the polymer precursor.
- 53. The composition of claim of claim 51, wherein at least a portion of the interstitial and vascular structure of the bone particles are infiltrated with the polymer precursor.
- 54. The composition of claim 51, wherein the bone particles are selected from the group consisting of nondemineralized bone particles, demineralized bone particles, and mixtures thereof.
- 55. The composition of claim 51, wherein the bone particles are obtained from a member of the group consisting of cortical bone, cancellous bone, cortico-cancellous bone, and mixtures thereof.
- 56. The composition of claim 51, wherein the bone particles are obtained from a member of the group consisting of autogenous bone, allogenic bone, xenogeneic bone, and mixtures thereof.
- 57. The composition of claim 51, wherein the bone particles are about 1% to about 25% by weight of the composite.
- 58. The composition of claim 51, wherein the bone particles are about 26% to about 50% by weight of the composite.
- 59. The composition of claim 51, wherein the bone particles are about 51% to about 75% by weight of the composite.
- 60. The composition of claim 51, wherein the bone particles are about 76% to about 99% by weight of the composite.
- 61. The composition of claim 51, wherein at least about 60% of the bone particles are elongate.
- 62. The composition of claim 51, wherein surfaces of the bone particles are modified.
- 63. The composition of claim 62, wherein the surfaces of the bone particles are derivatized with a silane coupling agent to the bone particles, wherein the silane coupling agent comprises an active group that is incorporated into the polymerized polymer precursor.
- 64. The composition of claim 63, wherein the active group is monofunctional or multifunctional.
- 65. The composition of claim 62, wherein the surfaces of the bone particles are derivatized with a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic material, a mineral, and any combination of the above to the bone particles.
- 66. The composition of claim 62, wherein the surfaces of the bone particles are derivatized with a silane coupling agent and wherein the silane coupling agent is derivatized with a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic material, a mineral, and any combination of the above.
- 67. The composition of claim 65 or 66, wherein the moiety is incorporated into the polymerized polymer precursor and linked to the polymerized polymer precursor by a member of covalent interactions, non-covalent interactions, and any combination of the above.
- 68. The composition of claim 62 wherein collagen fibers are exposed at the surface of the bone particles.
- 69. The composition of claim 68, wherein the exposed collagen fibers are frayed.
- 70. The composition of claim 68, wherein the exposed collagen fibers are cross-linked.
- 71. The composition of claim 68, wherein the exposed collagen fibers are derivatized with a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic molecule, a mineral, and any combination of the above.
- 72. The composition of claim 62 wherein the bone particles comprise a coating of calcium phosphate.
- 73. The composition of claim 51, wherein the polymerized polymer precursor is a polymer selected from the group consisting of biodegradable, non-biodegradable, co-polymers of biodegradable polymers, co-polymers of non-biodegradable polymers, and co-polymers of biodegradable and non-biodegradable polymers.
- 74. The composition of claim 73, wherein the polymer is selected from the group consisting of poly(phosphoesters), polysulfones, polyfumarates, polyphosphazines, poly(alkylene oxides), poly(arylates), poly(anhydrides), poly(hydroxy acids), polyesters, poly(ortho esters), polycarbonates, poly(propylene fumerates), poly(caprolactones), polyamides, polyamino acids, polyacetals, polylactides, polyglycolides, poly(dioxanones), polyhydroxybutyrate, polyhydroxyvalyrate, poly(vinyl pyrrolidone), biodegradable polycyanoacrylates, biodegradable polyurethanes, polysaccharides, tyrosine-based polymers, poly(pyrrole), poly(aniline), poly(thiophene), polystyrene, non-biodegradable polyurethanes, polyureas, poly(ethylene vinyl acetate), polypropylene, polymethacrylate, polyethylene, poly(ethylene oxide), and mixtures, adducts, and co-polymers thereof.
- 75. The composition of claim 51, wherein the plurality of bone particles are compressed together in a predetermined shape.
- 76. The composition of claim 75, wherein the compressed particles have a void volume not greater than 32%
- 77. The composition of claim 75, further comprising a member of a biocompatible binder, filler, fiber, plasticizer, biostatic/biocidal agent, surface active agent, biomolecule, small molecule, bioactive agent, and any combination of the above.
- 78. The composition of claim 75, wherein the shape is selected from a shape selected from the group consisting of a bone, a section of a bone, sheet, particle, sphere, strand, coiled strand, capillary network, film, fiber, mesh, plate, disk, cone, pin, screw, tube, cup, tooth, tooth root, strut, wedge, portion of wedge, cylinder, threaded cylinder, and rod.
- 79. A load-bearing osteoimplant, comprising:
a composite comprising a biocompatible polymer and bone particles, wherein: at least a portion of the bone particles are covalently linked to the polymer, and the biocompatible polymer is not a silane-modified aromatic polymer.
- 80. A load-bearing osteoimplant produced by the steps of:
providing a plurality of bone particles; combining the bone particles with a precursor of a biocompatible polymer; and polymerizing the polymer precursor to form a composite of a polymer and the bone particles.
- 81. The osteoimplant of claim 80, wherein polymerizing the polymer precursor comprises one or more of cross-linking the polymer precursor, increasing the molecular weight of the polymer precursor, and creating covalent bonds linking the polymerized polymer precursor with the bone particles.
- 82. The osteoimplant of claim 80, wherein the polymer precursor is selected from a monomer, a prepolymer, a flowable polymer, and a partially polymerized polymer.
- 83. The osteoimplant of claim 80, wherein, before the polymer precursor is polymerized, the ate least a portion of the vascular and interstitial structure of the bone particles are infiltrated with the polymer precursor.
- 84. The osteoimplant of claim 79 or 80, wherein the bone particles are selected from the group consisting of nondemineralized bone particles, demineralized bone particles, and mixtures thereof.
- 85. The osteoimplant of claim 79 or 80, wherein the bone particles are obtained from a member of the group consisting of cortical bone, cancellous bone, cortico-cancellous bone, and mixtures thereof.
- 86. The osteoimplant of claim 79 or 80, wherein the bone particles are obtained from a member of the group consisting of autogenous bone, allogenic bone, xenogeneic bone, and mixtures thereof.
- 87. The osteoimplant of claim 79 or 80, wherein the bone particles are about 1% to about 25% by weight of the composite.
- 88. The osteoimplant of claim 79 or 80, wherein the bone particles are about 26% to about 50% by weight of the composite.
- 89. The osteoimplant of claim 79 or 80, wherein the bone particles are about 51% to about 75% by weight of the composite.
- 90. The osteoimplant of claim 79 or 80, wherein the bone particles are about 76% to about 99% by weight of the composite.
- 91. The osteoimplant of claim 79 or 80, wherein at least about 60% of the bone particles are elongate.
- 92. The osteoimplant of claim 79 or 80, wherein surfaces of the bone particles are modified.
- 93. The osteoimplant of claim 92, wherein the surfaces of the bone particles are derivatized with a silane coupling agent to the bone particles, wherein the silane coupling agent comprises an active group that is incorporated into the polymer.
- 94. The osteoimplant of claim 93, wherein the active group is monofunctional or multifunctional.
- 95. The osteoimplant of claim 92, wherein the surfaces of the bone particles are derivatized with a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic material, a mineral, and any combination of the above to the bone particles.
- 96. The osteoimplant of claim 92, wherein the surfaces of the bone particles are derivatized with a silane coupling agent and wherein the silane coupling agent is derivatized with a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic material, a mineral, and any combination of the above.
- 97. The osteoimplant of claim 95 or 96, wherein the moiety is a member of incorporated into the polymerized polymer precursor and linked to the polymer by a member of covalent interactions, non-covalent interactions, and both of the above.
- 98. The osteoimplant of claim 92, wherein collagen fibers are exposed at the surface of the bone particles.
- 99. The osteoimplant of claim 98, wherein the exposed collagen fibers are frayed.
- 100. The osteoimplant of claim 98, wherein the exposed collagen fibers are cross-linked.
- 101. The osteoimplant of claim 98, wherein the exposed collagen fibers are derivatized with a moiety selected from the group consisting of a biomolecule, a small molecule, a bioactive agent, a non-biologically active material, an inorganic material, a mineral, and any combination of the above.
- 102. The osteoimplant of claim 92, wherein the bone particles comprise a coating of calcium phosphate.
- 103. The osteoimplant of claim 79 or 80, wherein the polymer is selected from the group consisting of biodegradable, non-biodegradable, co-polymers of biodegradable polymers, co-polymers of non-biodegradable polymers, and co-polymers of biodegradable and non-biodegradable polymers.
- 104. The osteoimplant of claim 103, wherein the polymer is selected from the group consisting of poly(phosphoesters), polysulfones, polyfumarates, polyphosphazines, poly(alkylene oxides), poly(arylates), poly(anhydrides), poly(hydroxy acids), polyesters, poly(ortho esters), polycarbonates, poly(propylene fumerates), poly(caprolactones), polyamides, polyamino acids, polyacetals, polylactides, polyglycolides, poly(dioxanones), polyhydroxybutyrate, polyhydroxyvalyrate, poly(vinyl pyrrolidone), biodegradable polycyanoacrylates, biodegradable polyurethanes, polysaccharides, tyrosine-based polymers, poly(pyrrole), poly(aniline), poly(thiophene), polystyrene, non-biodegradable polyurethanes, polyureas, poly(ethylene vinyl acetate), polypropylene, polymethacrylate, polyethylene, poly(ethylene oxide), and mixtures, adducts, and co-polymers thereof.
- 105. The osteoimplant of claim 79 or 80, wherein the composite has a shape selected from the group consisting of a bone, a section of a bone, sheet, plate, disk, cone, pin, particle, sphere, strand, coiled strand, capillary network, film, fiber, mesh, screw, tube, cup, tooth, tooth root, strut, wedge, portion of wedge, cylinder, threaded cylinder, and rod.
- 106. The osteoimplant of claim 79 or 80, wherein at least a portion of a surface of the composite is modified.
- 107. The osteoimplant of claim 106, wherein the portion of the surface is a member of the group consisting of oxidized, roughened, etched, associated with a biomolecule, associated with a small molecule, associated with a bioactive agent, associated with an inorganic material, associated with a mineral, and any combination of the above.
- 108. The osteoimplant of claim 79 or 80, wherein the osteoimplant comprises a plurality of pieces of composite fastened together in a predetermined shape.
- 109. The osteoimplant of claim 108, wherein the pieces of composite are fastened together with a member of an adhesive, a mechanical fastener, ultrasonic bonding, and any combination of the above.
- 110. The osteoimplant of claim 79 or 80, wherein the composite is shaped as particles, and wherein the particles are compressed in a predetermined shape.
- 111. The osteoimplant of claim 110, wherein the compressed composite particles have a void volume not greater than 32%
- 112. The osteoimplant of claim 110, further comprising a member of a biocompatible binder, filler, fiber, plasticizer, biostatic/biocidal agent, surface active agent, biomolecule, small molecule, bioactive agent, and any combination of the above before the step of compressing.
- 113. An osteoimplant, comprising:
a plurality of bone particles; and a biocompatible polymer, wherein the bone-polymer interface comprises at least a portion of the surfaces of the interstitial and vascular structure of the bone particles.
- 114. A composition, comprising:
at least one individual bone particle coated with a polymer precursor selected from a monomer, a flowable biocompatible polymer, a prepolymer, and a partially polymerized biocompatible polymer.
- 115. The composition of claim 114, wherein the bone particle is covalently linked to the polymer precursor.
- 116. The composition of claim 114, wherein the interstitial and vascular structure of the bone particle is at least partially infiltrated with the polymer precursor.
- 117. A method of preparing a bone particle composition, comprising coating at least one individual bone particle with a first polymer precursor.
- 118. The method of claim 117, further comprising combining a plurality of bone particles with a second polymer precursor and polymerizing the first and second polymer precursors to form a composite.
- 119. The method of claim 117, wherein the polymer precursor is selected from a monomer, a flowable biocompatible polymer, a prepolymer, and a partially polymerized biocompatible polymer
- 120. The method of claim 117, wherein coating comprises spray coating, tumbling, dipping, or using a fluidized bed.
- 121. The method of claim 117, further comprising infiltrating at least a portion of the interstitial and vascular structure of the bone particle with the polymer precursor.
Parent Case Info
[0001] This application claims the priority of U.S. Provisional application No. 60/402,998, filed Aug. 12, 2002, the entire contents of which are incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60402998 |
Aug 2002 |
US |