Tissue matrix system

• US 20060008530A1
• Filed: 07/11/2005
• Published: 01/12/2006
• Est. Priority Date: 07/12/2004
• Status: Active Grant

• Current Assignee: Isto Technologies Ii LLC
• Original Assignee: ISTO Technologies, Inc. (Isto Biologics, Inc.)
• Inventors: Spiro, Robert, Seyedin, Mitchell S.
• Granted Patent: US 8,192,759 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: C08L 5/00 Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present application discloses matrix compositions to support the repair of tissue defects such as an osteochondral injury. A matrix described herein comprises a polyester polymer entangled with a polysaccharide polymer. Also disclosed are methods of preparing a matrix, and methods of using a matrix in the repair of tissue. In certain configurations, a matrix can comprise a polyester cross-linked with a polysaccharide, which can be an oxidized polysaccharide. In some configurations, a matrix can further comprise one or more additional components, such as a growth factor.

Claims

1. A matrix for supporting repair of a tissue, the matrix comprising a polyester entangled with a polysaccharide.

2. A matrix in accordance with claim 1, wherein the polyester is selected from the group consisting of polylactic acid, polyglycolic acid, and a co-polymer comprising polylactic acid and polyglycolic acid.

3. A matrix in accordance with claim 1, wherein the polyester is a co-polymer comprising polylactic acid and polyglycolic acid.

4. A matrix in accordance with claim 3, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of about 5:

1 to about 2;

1.

5. A matrix in accordance with claim 4, wherein the weight ratio of polylactic acid to polyglycolic acid is about 3:

1.

6. A matrix in accordance with claim 1, wherein the polysaccharide is selected from the group consisting of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate, dextran, dextran sulfate, alginate, and a combination thereof.

7. A matrix in accordance with claim 6, wherein the polysaccharide is hyaluronic acid.

8. A matrix in accordance with claim 1, wherein the polysaccharide is an oxidized polysaccharide.

9. A matrix in accordance with claim 1, wherein the polysaccharide is covalently crosslinked.

10. A matrix in accordance with claim 1, wherein the polyester and the polysaccharide are in a weight ratio of from 99:

1 to 1;

99.

11. A matrix in accordance with claim 10, wherein the weight ratio of the polyester to the polysaccharide is from about 9:

1 to about 1;

9.

12. A matrix in accordance with claim 1, further comprising at least one growth factor.

13. A matrix in accordance with claim 12, wherein the at least one growth factor is selected from the group consisting of a TGF-β

, a bone morphogenetic protein, a growth differentiation factor, ADMP-1, a fibroblast growth factor, a hedgehog protein, an insulin-like growth factor, a platelet-derived growth factor, an interleukin, a colony-stimulating factor, and an activin.

14. A matrix in accordance with claim 12, wherein the at least one growth factor is a bone morphogenetic protein.

15. A matrix in accordance with claim 1, further comprising at least one collagen.

16. A method for preparing a matrix for repairing a tissue, the method comprising entangling in a mixture a polyester and a polysaccharide.

17. A method for preparing a matrix in accordance with claim 16, wherein the polyester is selected from the group consisting of polylactic acid, polyglycolic acid, and a co-polymer comprising polylactic acid and polyglycolic acid.

18. A method for preparing a matrix in accordance with claim 16, wherein the polyester is a co-polymer comprising polylactic acid and polyglycolic acid.

19. A method for preparing a matrix in accordance with claim 18, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of about 5:

1 to about 2;

1.

20. A method for preparing a matrix in accordance with claim 19, wherein the weight ratio of the polylactic acid to the polyglycolic acid is about 3:

1.

21. A method for preparing a matrix in accordance with claim 16, wherein the polysaccharide is selected from the group consisting of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate, dextran, dextran sulfate, alginate, and a combination thereof.

22. A method for preparing a matrix in accordance with claim 16, wherein the polysaccharide is hyaluronic acid.

23. A method for preparing a matrix in accordance with claim 16, further comprising oxidizing the polysaccharide.

24. A method for preparing a matrix in accordance with claim 16, further comprising covalently cross-linking the polysaccharide.

25. A method for preparing a matrix in accordance with claim 16, wherein the polyester and the polysaccharide are in a weight ratio of from 99:

1 to 1;

99.

26. A method for preparing a matrix in accordance with claim 25, wherein the weight ratio of the polyester to the polysaccharide is from about 9:

1 to about 1;

9.

27. A method for preparing a matrix in accordance with claim 16, further comprising adding to the mixture at least one growth factor.

28. A method for preparing a matrix in accordance with claim 27, wherein the at least one growth factor is selected from the group consisting of a TGF-β

, a bone morphogenetic protein, a growth differentiation factor, ADMP-1, a fibroblast growth factor, a hedgehog protein, an insulin-like growth factor, a platelet-derived growth factor, an interleukin, a colony-stimulating factor, and an activin.

29. A method for preparing a matrix in accordance with claim 27, wherein the at least one growth factor is a bone morphogenetic protein.

30. A method for preparing a matrix in accordance with claim 16, further comprising adding to the mixture at least one at least one collagen.

31. A method for preparing a matrix in accordance with claim 16, the method further comprising freezing and lyophilizing the mixture.

32. A method for preparing a matrix in accordance with claim 16, the method further comprising wet laying and air drying the mixture.

33. A method for promoting tissue growth in a mammal, the method comprising implanting in the mammal, at a site in need of tissue growth, a matrix comprising a polyester entangled with a polysaccharide.

34. A method for promoting tissue growth in accordance with claim 33, wherein the polyester is selected from the group consisting of polylactic acid, polyglycolic acid, and a co-polymer comprising polylactic acid and polyglycolic acid.

35. A method for promoting tissue growth in accordance with claim 33, wherein the polyester is a co-polymer comprising polylactic acid and polyglycolic acid.

36. A method for promoting tissue growth in accordance with claim 35, wherein the polylactic acid and the polyglycolic acid are in a weight ratio of about 5:

1 to about 2;

1.

37. A method for promoting tissue growth in accordance with claim 36, wherein the weight ratio of the polylactic acid to polyglycolic acid is about 3:

1.

38. A method for promoting tissue growth in accordance with claim 33, wherein the polysaccharide is selected from the group consisting of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate, dextran, dextran sulfate, alginate, and a combination thereof.

39. A method for promoting tissue growth in accordance with claim 33, wherein the polysaccharide is hyaluronic acid.

40. A method for promoting tissue growth in accordance with claim 33, wherein the polysaccharide is an oxidized polysaccharide.

41. A method for promoting tissue growth in accordance with claim 33, wherein the polysaccharide is covalently crosslinked.

42. A method for promoting tissue growth in accordance with claim 33, wherein the polyester and the polysaccharide are in a weight ratio of from 99:

1 to 1;

99.

43. A method for promoting tissue growth in accordance with claim 42, wherein the weight ratio of the polyester to the polysaccharide is from about 9:

1 to about 1;

9.

44. A method for promoting tissue growth in accordance with claim 33, wherein the matrix further comprises at least one growth factor.

45. A method for promoting tissue growth in accordance with claim 44, wherein the at least one growth factor is selected from the group consisting of a TGF-β

, a bone morphogenetic protein, a growth differentiation factor, ADMP-1, a fibroblast growth factor, a hedgehog protein, an insulin-like growth factor, a platelet-derived growth factor, an interleukin, a colony-stimulating factor, and an activin.

46. A method for promoting tissue growth in accordance with claim 44, wherein the at least one growth factor is a bone morphogenetic protein.

47. A method for promoting tissue growth in accordance with claim 33, wherein the matrix further comprises at least one collagen.

48. A method for promoting tissue growth in accordance with claim 33, wherein the tissue is selected from the group consisting of bone, cartilage, soft tissue and a combination thereof.

49. A method for promoting tissue growth in accordance with claim 33, wherein the mammal is a human in need of treatment.