Claims
- 1. A bonelike composite, comprising:
a. a hydrogel polymer scaffold,
wherein said polymer comprises a polymerized compound, —CH2—CR2—COOR1)n— wherein R1 is H or lower alkyl, R2 is H or a lower alkyl having from 1-20 carbon atoms and n is 10 to 100,000; b. a mineral deposit on the surface and the interior of the hydrogel polymer, said mineral deposit bound by ionic charges between calcium ions and polymer groups remaining after hydrolytic cleavage of R1, said mineral layer forming a nanocrystalline layer.
- 2. The composite of claim 1, wherein the hydrogel polymer scaffold has a water content between 20% and 100%.
- 3. The composite of claim 2, wherein said polymerized compound is pHEMA.
- 4. The composite of claim 2, wherein said polymer scaffold further comprising 0.1% to 50% a crosslinker.
- 5. The composite of claim 4, wherein said crosslinker is a compound of R3C(CH2)—C(O)—X—R4—X—C(O)-C(CH2)R3′, wherein R3 and R3′ can be identical or different and can be H or a lower alkyl, wherein the number of alkyl groups is less than 10; R4 is an alkyl chain, [—(CH2)n—Y—(CH2)n′—]m, wherein n and n′ are independently from 1 to 10, wherein m=1 to 500,000, X is O, S or N and Y is absent or O, S or NH.
- 6. The composite of claim 5, wherein said crosslinker is selected from the group consisting of diacrylates, diacrylamides, dimethacrylates or dimethacrylamides.
- 7. The composite of claim 6, wherein said crosslinker has a length varied from 1 to 500,000 repeating units.
- 8. The composite of claim 7, wherein said crosslinker bears a functional group which is selected from the group consisting of anionic groups, heteroatoms, polar ligands, aldehydes, ketones, phosphates, nucleic acids, amino acids, modified amino acids, glycosylated amino acids, phosphorylated amino acids, sulfated amino acids, peptides, proteins, carbohydrates, sugars, collagens, laminins, extracellular matrix components, biodegradable motifs and polyethylene glycols.
- 9. The composite of claim 8, wherein said crosslinker is ethylene glycol dimethacrylate, ethylene glycol dimethacrylamide or compound of CH3C(CH2)—CO—O—CH2CH3—O—CO—(CH2)CCH3 or CH3C(CH2)—CO—N—CH2CH3—N—CO—(CH2)CCH3.
- 10. The composite of claim 1, wherein said polymer scaffold further comprising 0.1% to 50% a co-monomer.
- 11. The composite of claim 10, wherein said co-monomer is a methacrylate or a methacrylamide.
- 12. The composite of claim 11, wherein said co-monomer bears a functional group which is selected from the group consisting of anionic groups, polar ligands, aldehydes, ketones, phosphates, nucleic acids, amino acids, modified amino acids, glycosylated amino acids, phosphorylated amino acids, sulfated amino acids, peptides, proteins, carbohydrates, collagens, laminins, extracellular matrix components, biodegradable motifs and polyethylene glycols.
- 13. The composite of claim 1, wherein said mineralization mixture is comprised of inorganic components selected from the group consisting of Ca2+, PO43−, OH−, CO32−, Cl− and other trace inorganic elements.
- 14. The composite of claim 13, wherein the ratio of Ca2+ to PO43− ions is between 0.5 and 4.
- 15. The composite of claim 14, wherein the ratio of Ca2+ to PO43− ions is between 1 and 2.
- 16. The composite of claim 15, wherein said mineralization mixture is selected from the group consisting of crystalline, nanocrystalline or amorphous hydroxyapatite (Ca10(PO4)6(OH)2), calcium carbonate, dicalcium phosphate, tricalcium phosphate, octacalcium phosphate, calcium phosphates having a stoichiometry that ranges from CaO-2P2O5 to 4CaO—P2O5 and solubility behavior, under acidic and basic conditions, similar to that of hydroxyapatite.
- 17. The composite of claim 13, wherein the hydrolysis of R1 is mediated by contacting the hydrogel polymer with a solution comprising said mineralization mixture and a mild base capable of modulating a slow increase in pH.
- 18. The composite of claim 17, wherein said initial mineral deposition is a nanocrystalline or amorphous mineral deposit.
- 19. The composite of claim 18, wherein said extended mineral layer is about 1 to 7 μm in thickness.
- 20. The composite of claim 19, attached to a bone in a vertebrate subject, or deposited upon an implant, or deposited upon organic-inorganic hybrid materials.
- 21. A composite structure prepared from:
a base monomer, —(CH2—CR2—COOR1)n—, wherein R1 is selected from the group consisting of H or lower alkyl; R2 is selected from the group consisting of H or lower alkyl; and n is 10 to 100,000; a cross linking agent selected from the group consisting of diacrylates, diacrylamides, methacrylates and methacrylamides; and a mineralization mixture of calcium and phosphate, wherein said calcium and phosphate are in a ratio of 1Ca to 2P.
- 22. A method for preparing a bonelike composite, comprising:
a. forming a crosslinked hydrogel polymer, having a surface and an interior, comprised of a polymerized base monomer having ester-containing side chains, b. hydrolyzing a percentage of the ester side chains to form reactive acidic groups on the surface and the interior of the hydrogel; and c. contacting said reactive acidic groups with a mineral to form a nanocrystalline or amorphous mineral deposit on said acidic surface and interior of the hydrogel.
- 23. The method according to claim 22, wherein said base monomer has a structure, —CH2—CR2—COOR1)n—, wherein R1 is a lower alkyl group, wherein R2 can be H or any lower alkyl group, wherein n is 10 to 100,000.
- 24. The method according to claim 23, wherein said base monomer is 2-hydroxyethyl methacrylate.
- 25. The method according to claim 22, wherein said crosslinking is 0.1% to 50%.
- 26. The method according to claim 25, wherein said crosslinker has a structure, R3C(CH2)—C(O)—X—R4—X—C(O)—(CH2)CR3, wherein R3 and R3′ can be H or a lower alkyl, wherein the number of alkyl groups is less than 10; R4 is [—(CH2)n—Y—(CH2)n′—]m, wherein n and n′ are independently from 1 to 10, wherein m=1 to 500,000, wherein each R4 alkyl group can be independently the same or different; wherein X is O, S or N and Y is absent or O, S or NH.
- 27. The method according to claim 26, wherein said crosslinker is selected from the group consisting of dimethacrylate, dimethacrylamide, di acrylate or diacrylamide.
- 28. The method according to claim 27, wherein said crosslinker is ethylene glycol dimethacrylate, ethylene glycol dimethacrylamide or a compound of R3C(CH2)—C(O)—X—R4—X—C(O)—(CH2)CR3, wherein R3 and R3′ are both CH3, R4 is CH2CH3 and X is O.
- 29. The method according to claim 22, wherein said polymer further comprises 0.1% to 50% a co-monomer.
- 30. The method according to claim 29, wherein said co-monomer is a methacrylate or a methacrylamide.
- 31. The method according to claim 30, wherein said co-monomer bears a functional group which is selected from the group consisting of anionic groups, polar ligands, aldehydes, ketones, phosphates, nucleic acids, amino acids, modified amino acids, phosphorylated amino acids, glycosylated amino acids, sulfated amino acids, peptides, proteins, carbohydrates, sugars, collagens, laminins, extracellular matrix components, biodegradable motifs and polyethylene glycols.
- 32. The method of claim 22, wherein said hydrolysis of R1 groups is catalyzed by the gradual addition or in situ generation of an acid, base or an esterase enzyme that will thermally or aqueously degrade to release acid or base in a mild fashion in the interior and on the surface of the hydrogel.
- 33. The method of claim 32, wherein said base is selected from the group consisting of ammonia, ammonium hydroxide, urea, piperidine, imidazole, potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate,and pyridine.
- 34. The method of claim 33, wherein said acid is selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, formic acid, citric acid, carboxylic acid, and organic acids miscible with water.
- 35. The method according to claim 34, wherein said hydrolysis of R1 groups is caused by gradual heating of urea in water.
- 36. The method according to claim 35, wherein said gradual heating of urea is from room temperature to 95° C. at a heating rate between 0.1° C./min and 1° C./min.
- 37. The method according to claim 36, wherein said heating rate is a constant heating rate between 0.2 and 0.5° C./min.
- 38. The method according to claim 37, wherein said heating of urea is without agitation or stirring.
- 39. The method according to claim 22, wherein said mineral deposited into and on the surface of the hydrogel is a calcium phosphate.
- 40. The method according to claim 39, wherein the ratio of calcium to phosphate in said mineral is between 0.5 and 4.
- 41. The method according to claim 40, wherein said mineral is nanocrystalline or amorphous hydroxyapatite (Ca10(PO4)6(OH)2).
- 42. A method for preparing a bonelike composite, comprising:
a. contacting a hydrogel scaffold with a solution comprised of urea and a mineral, wherein said hydrogel scaffold is comprised of a crosslinker and a monomer, wherein said monomer is a substituted or unsubstituted polyacrylate derivative having ester-containing side chains and said crosslinker is selected from the group consisting of dimethacrylate, dimethacrylamide, diacrylate or diacrylamide; b. heating said solution to decompose urea and increase pH to hydrolyze said ester-containing side chains to form reactive acidic groups on the surface and in the interior of the hydrogel scaffold; and c. forming a mineral deposit on the surface and interior of the hydrogel, wherein mineral deposition occurs as a result of nucleation at the acidic groups on the surface and interior of the hydrogel.
- 43. The method of claim 42, wherein said mineral is selected from the group consisting of: hydroxyapatite, calcium carbonate, calcium phosphates, dicalcium phosphate, tricalcium phosphate, and octacalcium phosphate.
- 44. The method of claim 43, wherein the ratio of calcium to phosphate in the mineral deposit is between 0.5 and 4, preferably from 1 to 2, wherein the calcium phosphate stoichiometry can range from CaO-2P2O5 to 4CaO—P2O5.
- 45. The method of claim 44, wherein the hydrogel is formed from HEMA monomer and a crosslinker selected from the group consisting of ethylene glycol dimethacrylate or ethylene glycol dimethacrylamide.
- 46. The method of claim 45, wherein the pH is increased from about 1-3 to about 7-9.
- 47. The method according to claim 46, wherein said gradual heating of said solution is from room temperature to 95° C. at a heating rate between 0.1° C./min and 1° C./min.
- 48. The method according to claim 47, wherein said heating rate is a constant heating rate between 0.2 and 0.5° C./min.
- 49. The method according to claim 47, wherein said heating of solution is without agitation or stirring.
- 50. The method according to claim 49, wherein said heating of said solution is extended to about 10 to 12 hours to form an extended mineral layer upon said mineral deposit.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from U.S. Provisional Patent Application No. 60/434,596, filed on Dec. 18, 2002, which is hereby incorporated by reference in its entirety.
STATEMENT OF GOVERNMENTAL SUPPORT
[0002] This invention was made during work supported by U.S. Department of Energy under Contract No. DE-AC03-76SF00098. The government has certain rights in this invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60434596 |
Dec 2002 |
US |