Claims
- 1. A composite biomaterial comprising:
(a) a matrix including (i) a calcium phosphate composition that can cure in vivo, (ii) a thermoplastic polymer, or (iii) any combination of (i) and/or (ii); and (b) anisometric calcium phosphate reinforcement particles dispersed within the matrix, wherein the particles are aligned within the matrix.
- 2. The composite of claim 1, wherein the reinforcement particles have a mean aspect ratio (length along c-axis/length along a-axis) of from about 5 to about 50.
- 3. The composite of claim 2, wherein the mean aspect ratio is from about 10 to about 20.
- 4. The composite of claim 1, wherein at least some of the reinforcement particles are shaped like whiskers.
- 5. The composite of claim 1, wherein at least some of the reinforcement particles are shaped like platelets.
- 6. The composite of claim 1, wherein the reinforcement particles are present in an amount of from about 1% by volume of the composite to about 60% by volume of the composite.
- 7. The composite of claim 6, wherein the reinforcement particles are present in an amount of from about 40% by volume of the composite to about 60% by volume of the composite.
- 8. The composite of claim 1, wherein the reinforcement particles have dimensions of from about 1 micrometer to about 500 micrometers along the taxis and from about 0.02 micrometers to about 20 micrometers along the a-axis.
- 9. The composite of claim 8, wherein the reinforcement particles have a length of from about 5 micrometers to about 50 micrometers along the c-axis and from about 0.1 micrometers to about 10 micrometers along the a-axis.
- 10. The composite of claim 1, wherein the matrix includes at least one thermoplastic that is non-bioresorbable.
- 11. The composite of claim 10, wherein the non-bioresorbable thermoplastic is selected from the group consisting of polyethylene, high density polyethylene (HDPE), ultra high molecular weight polyethylene (UHMWPE), low density polyethylene (LDPE), polybutylene, polystyrene, polyurethane, polyacrylates, polymethacrylates, polypropylene, copolymers thereof, and blends thereof.
- 12. The composite of claim 1, wherein the matrix includes at least one thermoplastic that is bioresorbable.
- 13. The composite of claim 12, wherein the bioresorbable thermoplastic is selected from the group consisting of poly(DL-lactide) (DLPLA), poly(L-lactide) (LPLA), poly(glycolide) (PGA), poly(e-caprolactone) (PCL), poly(dioxanone) (PDO), poly(glyconate), poly(hydroxybutyrate) (PHB), poly(hydroxyvalerate (PHV), poly(orthoesters), poly(carboxylates), poly(propylene fumarate), poly(phosphates), poly(carbonates), poly(anhydrides), poly(iminocarbonates), poly(phosphazenes), copolymers or blends thereof, and combinations thereof.
- 14. The composite of claim 1, wherein the composite includes at least one non-bioresorbable thermoplastic and at least one bioresorbable thermoplastic.
- 15. The composite of claim 14, wherein the bioresorbable thermoplastic is graded from a surface of the matrix to an inner core of the matrix.
- 16. The composite of claim 1, wherein the matrix includes at least one calcium phosphate compound.
- 17. The composite of claim 16, wherein the matrix includes particulate or dissolved bioresorbable or non-bioresorbable thermoplastic.
- 18. The composite of claim 1, wherein at least some of the reinforcement particles are bioresorbable.
- 19. The composite of claim 18, wherein the bioresorbable reinforcement particles are graded from a surface of the matrix to an inner core of the matrix.
- 20. The composite of claim 1, wherein the matrix includes the calcium phosphate composition, and wherein the calcium phosphate composition is selected from the group consisting of amorphous calcium phosphate, biphasic calcium phosphate, calcium phosphate, dicalcium phosphate, dicalcium phosphate dihydrate, calcium hydroxyapatite. carbonated calcium hydroxyapatite, monocalcium phosphate, monocalcium phosphate monohydrate, octacalcium phosphate, tricalcium phosphate, alpha-tricalcium phosphate, beta-tricalcium phosphate, tetracalcium phosphate, and combinations thereof.
- 21. The composite of claim 20, wherein the calcium phosphate composition includes at least one dopant.
- 22. The composite of claim 1, wherein the anisometric calcium phosphate reinforcement particles are selected from the group consisting of amorphous calcium phosphate, biphasic calcium phosphate, calcium phosphate, dicalcium phosphate, dicalcium phosphate dihydrate, calcium hydroxyapatite, carbonated calcium hydroxyapatite, monocalcium phosphate, monocalcium phosphate monohydrate, octacalcium phosphate, tricalcium phosphate, alpha-tricalcium phosphate, beta-tricalcium phosphate, tetracalcium phosphate, and combinations thereof.
- 23. The composite of claim 22, wherein at least some of the anisometric calcium phosphate reinforcement particles include at least one dopant.
- 24. The composite of claim 1, further comprising at least one surface-active agent.
- 25. The composite of claim 1, further comprising at least one additive selected from the group consisting of growth factors, transcription factors, matrix metalloproteinases, peptides, proteins, and combinations thereof.
- 26. A prosthesis for replacement of bone comprising the composite of claim 1.
- 27. A method of preparing a composite biomaterial comprising (a) a matrix including at least one calcium phosphate composition that can be cured in vivo and (b) anisometric calcium phosphate reinforcement particles arranged within the matrix, said method comprising:
providing the anisometric calcium phosphate reinforcement particles; preparing the calcium phosphate composition from at least one calcium- containing compound and at least one phosphate-containing compound, wherein at least one of the calcium-containing compound and phosphate-containing compound is derived by a hydrothermal reaction; and combining the anisometric calcium phosphate reinforcement particles with the calcium phosphate composition or with at least one of the calcium-containing compound or phosphate-containing compound prior to formation of the calcium phosphate composition.
- 28. The method of claim 27, wherein the anisometric calcium phosphate reinforcement particles are provided via a hydrothermal reaction.
- 29. The method of claim 29, wherein at least one of the calcium-containing compound or phosphate-containing compound is in the form of particles having a mean diameter of less than about 1 micrometer.
- 30. The method of claim 29, wherein at least one of the calcium-containing compound or phosphate-containing compound is in the form of particles having a mean diameter of from about 1 nanometers to about 500 nanometers.
- 31. The method of claim 27, wherein each of said calcium-containing compound and phosphate-containing compound is derived by a hydrothermal reaction.
- 32. The method of claim 27, wherein the anisometric calcium phosphate reinforcement particles are mixed with at least one of the calcium-containing compound or phosphate-containing compound prior to formation of the calcium phosphate composition.
- 33. The method of claim 27, wherein the anisometric calcium phosphate reinforcement particles are added after the calcium phosphate composition is formed.
- 34. The method of claim 27, wherein the calcium containing compound is selected from the group consisting of calcium hydroxide, calcium nitrate, calcium chloride, calcium carbonate, calcium lactate, calcium acetate, calcium citrate, calcium sulfate, calcium fluoride, calcium oxalate, amorphous calcium phosphate, biphasic calcium phosphate, calcium phosphate, dicalcium phosphate, dicalcium phosphate dihydrate, calcium hydroxyapatite, carbonated calcium hydroxyapatite, monocalcium phosphate, monocalcium phosphate monohydrate, octacalcium phosphate, tricalcium phosphate, alpha-tricalcium phosphate, beta-tricalcium phosphate, tetracalcium phosphate, and combinations thereof.
- 35. The method of claim 27, wherein the phosphate-containing compound is selected from the group consisting of phosphoric acid, fluorophosphoric acid, sodium orthophosphate, potassium orthophosphate, ammonium orthophosphate, amorphous calcium phosphate, biphasic calcium phosphate, calcium phosphate, dicalcium phosphate, dicalcium phosphate dihydrate, calcium hydroxyapatite, carbonated calcium hydroxyapatite, monocalcium phosphate, monocalcium phosphate monohydrate, octacalcium phosphate, tricalcium phosphate, alpha-tricalcium phosphate, beta-tricalcium phosphate, tetracalcium phosphate, and combinations thereof.
- 36. A method of preparing a composite biomaterial comprising (a) a matrix including at least one thermoplastic polymer and (b) anisometric calcium phosphate reinforcement particles arranged within the matrix, said method comprising:
providing the anisometric calcium phosphate reinforcement particles; providing the polymer; co-processing the polymer and the calcium phosphate reinforcement particles to obtain a substantially uniform mixture thereof; and deforming and/or densifying the mixture to form the composite biomaterial.
- 37. The method of claim 36, wherein the anisometric calcium phosphate reinforcement particles are provided via a hydrothermal reaction.
- 38. The method of claim 36, wherein said providing the polymer includes providing particles of the polymer in a suspension, wherein said providing the anisometric calcium phosphate reinforcement particles includes providing the reinforcement particles in the suspension or in a second suspension, and wherein said co-processing includes wet co-consolidation of the calcium phosphate reinforcement particles and the polymer particles to form a preform.
- 39. The method of claim 38, wherein the polymer particles are produced by dissolving the polymer in a solvent under mixing, followed by precipitation or gelation of the polymer from the solution, followed by solvent removal.
- 40. The method of claim 39, wherein the solvent removal is by way of vacuum oven drying, distillation and collection, or freeze drying.
- 41. The method of claim 36, wherein said providing the polymer includes providing a foam of polymer having continuous open porosity, and wherein said co-processing includes infiltrating the polymer foam with a suspension of the calcium phosphate reinforcement particles to form a preform.
- 42. The method of claim 41, wherein the polymer foam is produced by dissolving the polymer in a solvent under mixing, followed by precipitation or gelation of the polymer from the solution, followed by solvent removal.
- 43. The method of claim 42, wherein the solvent removal is by way of vacuum oven drying, distillation and collection, or freeze drying.
- 44. The method of claim 36, wherein said providing the anisometric calcium phosphate reinforcement particles includes providing a porous compact of the calcium phosphate reinforcement particles, said providing the polymer includes providing a molten or solvated polymer or as a polymerizing mixture comprising monomer and initiator, and, optionally polymer powder, co-initator, and/or stabilizer, and wherein said co-processing includes infiltrating the porous compact of the calcium phosphate reinforcement particles with the polymer.
- 45. The method of claim 44, wherein the porous compact of the calcium phosphate reinforcement particles is produced by dry pressing calcium phosphate particles and sintering the dry pressed particles to form the compact.
- 46. The method of claim 45, wherein the sintering is at a temperature of from about 600° C. to about 1000° C.
- 47. The method of claim 36, wherein said providing the polymer includes mixing monomer with an initiator, and, optionally, polymer powder and co-initiator, to form a polymer-forming mixture, and wherein said co-processing includes polymerizing and hardening the mixture in situ.
- 48. The method of claim 47, wherein said initiator and/or co-initiator is selected from the group consisting of benzoyl peroxide, dimethylaniline, ascorbic acid, cumene hydroperoxide, tributylborane, sulfinic acid, 4-cyanovaleric acid, potassium persulfate, dimethoxybenzoine, benzoic-acid-phenylester, N,N-dimethyl p-toluidine, dihydroxy-ethyl-p-toluidinebenzoyl peroxide, and any combination thereof.
- 49. The method of claim 47, wherein said monomer is selected from the group consisting of methylmethacrylate (MMA), 2,2′-bis(methacryloylethoxyphenyl) propane (bis-MEEP), bisphenol a polyethylene glycol diether dimethacrylate (bis-EMA), urethane dimethacrylate (UDMA), diphenyloxymethacrylate (DPMA), n-butylmethacrylate, tri(ethylene glycol) dimethacrylate (TEG-DMA), bisphenol a hydroxypropylmethacrylate (bis-GMA), and any combination thereof.
- 50. The method of claim 47, wherein said providing the polymer includes adding a stabilizer to prevent premature polymerization of the polymer.
- 51. The method of claim 50, wherein said stabilizer is selected from hydroquinone, 2-hydroxy-4-methoxy-benzophenone, or combinations thereof.
- 52. The method of claim 47, wherein said co-processing comprises combining said anisometric calcium phosphate reinforcement particles with said polymer-forming mixture prior to mixing the components thereof.
- 53. The method of claim 47, wherein said co-processing comprises combining said anisometric calcium phosphate reinforcement particles with said polymer-forming mixture during polymerization.
- 54. The method of claim 36, wherein the deforming and/or densifying includes aligning the calcium phosphate reinforcement particles morphologically and/or crystallographically.
- 55. The method of claim 36, wherein the deforming and/or densifying occurs thermo-mechanically or mechanically.
- 56. The method of claim 56, wherein the thermo-mechanically deforming and/or densifying includes channel die forging.
- 57. The method of claim 56, wherein the thermo-mechanically or mechanically deforming and/or densifying includes compression molding or die pressing.
- 58. The method of claim 56, wherein the thermo-mechanically deforming and/or densifying includes injection molding.
- 59. The method of claim 56, wherein the thermo-mechanically deforming and/or densifying includes extrusion or pultrusion.
- 60. The method of claim 56, wherein the mechanically deforming and/or densifying includes the viscous flow of a molten or polymerizing polymer matrix.
- 61. The method of claim 60, wherein the viscous flow is achieved by percutaneous or surgical injection, channel die forging, compression molding, injection molding, or extrusion.
- 62. The method of claim 36, further comprising adding a surface-active agent.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of U.S. application No. 60/179,238, filed on Jan. 31, 2000, which is hereby incorporated in its entirety by reference.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US01/03219 |
1/31/2001 |
WO |
|