Polymer composite compositions

• US 20020037940A1
• Filed: 06/01/2001
• Published: 03/28/2002
• Est. Priority Date: 06/01/2000
• Status: Active Grant

• Current Assignee: Shriners Hospitals For Children (Shriner's International Headquarters Incorporated)
• Original Assignee: Shriners Hospitals For Children (Shriner's International Headquarters Incorporated)
• Inventors: Koob, Thomas J., Hernandez, Daniel J.
• Granted Patent: US 6,565,960 B2
• Time in Patent Office: Days
• US Class Current: 521/55
• CPC Class Codes: C08H 1/06 derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: D06M 13/152 having a hydroxy group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: D06M 2101/14 Collagen fibres
• CPC Class Codes: Y10T 428/24994 Fiber embedded in or on the surface of a polymeric matrix
• CPC Class Codes: Y10T 428/249953 Composite having voids in a component [e.g., porous, cellular, etc.]
• CPC Class Codes: Y10T 428/249986 Void-containing component contains also a solid fiber or solid particle
• CPC Class Codes: Y10T 428/249987 With nonvoid component of specified composition
• CPC Class Codes: Y10T 428/249999 Differentially filled foam, filled plural layers, or filled layer with coat of filling material
• CPC Class Codes: Y10T 428/31826 Of natural rubber

Abstract

The invention relates to methods of treating mixtures containing polymeric materials, e.g., collagen, to form a polymer that intercalates into the polymeric material. The treatment provides greater tensile strength to the mixture, among other advantages. The polymer is formed of a monomeric unit having at least one catechol group that is oxidized to a quinone upon polymerization.

Claims

1. A method of treating a polymeric material, the method comprising

providing a mixture comprising the polymeric material and a monomer comprising a first catechol group and a reactive group;

oxidizing the mixture; and

polymerizing the monomer via the first catechol group and the reactive group to form a polymer in which the first catechol group has been oxidized to a quinone group, wherein the polymer intercalates into the polymeric material.

2. The method of claim 1, wherein the reactive group is the second catechol group.

3. The method of claim 2, wherein the polymer is a homopolymer of the monomer.

4. The method of claim 1, wherein the polymeric material is collagen.

5. The method of claim 4, further comprising digesting the collagen with a protease before the oxidizing and polymerizing steps.

6. The method of claim 4, wherein the collagen is in a form selected from the group consisting of microfibrils, fibrils, natural fibers, and synthetic fibers.

7. The method of claim 1, wherein, in the oxidizing step, oxygen is introduced into the mixture in the form of dissolved molecular oxygen.

8. The method of claim 1, wherein, in the oxidizing step, the oxygen is introduced into the mixture in the form of periodate.

9. The method of claim 8, wherein the periodate is sodium meta-periodate.

10. The method of claim 1, wherein the reactive group is an aldehyde group.

11. The method of claim 1, wherein the monomer is selected from the group consisting of 2,3-dihydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, rosemarinic acid, nordihydroguaiaretic acid, and the compound having the following structure.

12. The method of claim 11, wherein the monomer is nordihydroguaiaretic acid.

13. The method of claim 1, wherein the reactive group is a second catechol group and the monomer further comprises two additional catechol groups.

14. The method of claim 4, wherein the collagen is at least 50% by weight of the mixture.

15. The method of claim 14, wherein the collagen is at least 90% by weight of the mixture.

16. The method of claim 1, wherein the compound further comprises a 2,3-dimethylbutylene group between the first catechol group and the reactive group.

17. The method of claim 1, further comprising removing unpolymerized monomer from the mixture after the polymerizing step.

18. A method of increasing the tensile strength of a composition comprising collagen, the method comprising adding a monomer comprising a first catechol group and a reactive group selected from the group consisting of a second catechol group and an aldehyde group to the composition to form a mixture;

and treating the mixture using the method of claim 1.

19. A method of increasing the protease resistance of a composition comprising collagen, the method comprising adding a monomer comprising a first catechol group and a reactive group selected from the group consisting of a second catechol group and an aldehyde group to the composition to form a mixture;

and treating the mixture using the method of claim 1.

29. The method of claim 1 wherein:

the polymeric material is collagen; and

the monomer further comprises a linker of at least three carbon atoms between the first catechol group and the reactive group, wherein no more than one peptide bond separates the first catechol group from the reactive group.

32. The method of claim 1, wherein

the polymeric material is collagen;

and

the reactive group of the monomer is not a carboxyl group or a primary amine.

36. The method of claim 1, wherein

the polymeric material is collagen;

and

the reactive group is selected from the group consisting of a second catechol group and an aldehyde group.

20. A composition comprising collagen and a polymer that intercalates into the collagen, the polymer comprising monomers, each monomer comprising a first quinone group, a second quinone group, and a linker of at least three carbon atoms between the first quinone group and the second quinone group, wherein no more than one peptide bond separates the first quinone group from the second quinone group.

21. The composition of claim 20, wherein the polymer is a homopolymer of the monomers, each monomer attached to at least one other monomer via a covalent bond formed between a ring carbon of a quinone group of one monomer and a ring carbon of a quinone group of another monomer.

22. The composition of claim 20, wherein the monomer further comprises a 2,3-dimethylbutylene group between the first quinone group and the second quinone group.

23. The composition of claim 20, wherein the monomer further comprises two additional quinone groups.

24. The composition of claim 20, wherein the collagen is selected from the group consisting of sea cucumber dermis collagen, bovine tendon collagen, and gelatin.

25. The composition of claim 20, wherein the collagen is in a form selected from the group consisting of microfibrils, fibrils, natural fibers, and synthetic fibers.

26. The composition of claim 20, wherein the collagen is at least 50% by weight of the composition.

27. The composition of claim 26, wherein the collagen is at least 90% by weight of the composition.

28. The composition of claim 20, wherein the composition is in the form of a synthetic fiber having a tensile strength of at least 80 MPa.

30. A compound comprising three catechol groups and a linker, wherein each catechol group resides at a terminal carbon of the linker.

31. The compound of claim 30, wherein the compound has the following structure.

33. A composition comprising collagen and a polymer that intercalates into the collagen, the polymer comprising monomers, each monomer comprising a first quinone group, and a second reacted group, provided that the reacted group is not an amino or carbonyl group participating in a peptide bond within the monomer.

35. The method of claim 34, wherein the reactive group is a catechol group.

37. The method of claim 36, wherein the reactive group is a second catechol group.

38. The method of claim 36, wherein the collagen is selected from the group consisting of sea cucumber dermis collagen, bovine tendon collagen, and gelatin.

40. The composition of claim 39, wherein the catechol-containing monomer is a monomer comprising a first catechol group and a reactive group selected from the group consisting of a second catechol group and an aldehyde group.

41. The composition of claim 39, wherein the catechol-containing monomer is nordihydroguaiaretic acid, 2-Arm, 3-Arm, 4-Arm, or 9-Arm.

34. A method of making a polymer composition comprising combining collagen and a polymer that intercalates into the collagen, the polymer comprising monomers, each monomer comprising a catechol group, a reactive group, and a linker of at least three carbon atoms between the catechol group and the reactive group.

39. A composition comprising a polymeric material and a polymer made by the polymerization of a catechol-containing monomer.

42. A composition comprising:

a catechol-containing monomer treated collagen fiber; and

a catechol-containing monomer treated collagen foam.

43. The composition of claim 42, wherein the fiber is surrounded by the foam.

44. The composition of claim 42, wherein the foam comprises pores of a size to allow infiltration of cells into the foam.

45. The composition of claim 44, wherein the composition further comprises cells.

46. The composition of claim 45, wherein the cells are fibroblasts, mesenchymal stem cells, chondrocytes, or molecularly engineered cells.

47. The composition of claim 42, wherein the catechol-containing monomer is nordihydroguaiaretic acid, 2-Arm, 3-Arm, 4-Arm, or 9-Arm.

48. A method of engineering tissue comprising use of the composition of claim 42.

49. The method of claim 48, wherein the tissue is tendon.

50. A method of making a composition of claim 42, comprising combining a catechol-containing monomer treated collagen fiber;

and a catechol-containing monomer treated collagen foam.

51. The method of claim 50, wherein the catechol-containing monomer treated collagen fiber is combined with collagen foam, and the resulting composition is treated with a catechol-containing monomer.