Collagen scaffolds, medical implants with same and methods of use

• US 20080020012A1
• Filed: 06/22/2007
• Published: 01/24/2008
• Est. Priority Date: 06/22/2006
• Status: Abandoned Application

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Ju, Young, Koob, Thomas, Moussy, Francis
• Application Number:
  US11/821,320
• Publication Number:
  US 20080020012A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61L 2400/02 Treatment of implants to prevent calcification or mineralisation in vivo
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/044 Collagen
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/129 containing macromolecular fillers
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

The subject invention concerns non-degradable three dimensional porous collagen scaffolds and coatings. These scaffolds can be prepared around sensors for implantation into a body. A specific embodiment of the invention concerns implantable glucose sensors. Sensors comprising a collagen scaffold of the invention have improved biocompatibility by minimizing tissue reactions while stimulating angiogenesis. The subject invention also concerns methods for preparing collagen scaffolds of the invention. The subject invention also concerns sensors that have a collagen scaffold of the invention around the exterior of the sensor.

Claims

1. A biocompatible collagen scaffold and/or coating for use with a device implantable in the body or tissue of a person or animal, wherein said collagen scaffold or coating is embedded within a polymer matrix.

2. The collagen scaffold according to claim 1, wherein said collagen scaffold is treated with a cross-linking compound comprising a reactive catechol at a pH sufficient to produce a reactive quinone.

3. The collagen scaffold according to claim 2, wherein said reactive catechol is a di-catechol.

4. The collagen scaffold according to claim 1, wherein said collagen scaffold is embedded in a nordihydroguaiaretic acid (NDGA) bisquinone polymer matrix.

5. The collagen scaffold according to claim 1, wherein said device comprises a sensor.

6. The collagen scaffold according to claim 5, wherein said sensor is a glucose sensor.

7. The collagen scaffold according to claim 1, wherein said collagen scaffold comprises open pores of between about 10 μ

m to about 200 μ

m in diameter (mean).

8. The collagen scaffold according to claim 7, wherein the mean pore size of said collagen scaffold is about 60 μ

m or less in diameter.

9. The collagen scaffold according to claim 7, wherein the mean pore size of said collagen scaffold is between about 40 μ

m and about 80 μ

m in diameter.

10. The collagen scaffold according to claim 1, wherein said scaffold comprises at least one of an antimicrobial, anti-inflammatory, and/or angiogenic compound, drug or growth factor.

11. A method for preparing a device for implantation into the body or tissue of a person or animal, said method comprising placing a biocompatible collagen scaffold or coating on said device, wherein said collagen scaffold or coating is embedded within a polymer matrix.

12. The method according to claim 11, wherein said method comprises:

a) contacting said device with a collagen containing solution;

b) drying said collagen solution on said device; and

c) embedding said collagen on said device in a polymer matrix.

13. The method according to claim 12, wherein said collagen is embedded in said matrix using a reactive catechol at a pH sufficient to produce a reactive quinone.

14. The method according to claim 13, wherein said reactive catechol is a dicatechol.

15. The method according to claim 14, wherein said dicatechol is NDGA.

16. The method according to claim 12, wherein steps (a) and (b) of said method are repeated at least one time.

17. The method according to claim 12, wherein steps (a) and (b) of said method are repeated at least two to four times.

18. The method according to claim 12, wherein said drying step comprises freeze-drying.

19. The method according to claim 12, wherein said collagen embedded in said matrix is subsequently freeze-dried.

20. The method according to claim 12, wherein said collagen containing solution of step (a) comprises about 1% (w/v) collagen.

21. The method according to claim 12, wherein said collagen scaffold comprises open pores of about 10 μ

m to about 200 μ

m in diameter (mean).

22. The method according to claim 21, wherein the mean pore size of the collagen scaffold is about 60 μ

m or less in diameter.

23. The method according to claim 21, wherein the mean pore size of the collagen scaffold is between 40 μ

m and 80 μ

m in diameter.

24. A method for providing an implantable device with a biocompatible collagen coating or scaffold, wherein said collagen scaffold or coating is embedded within a polymer matrix, said method comprising:

a) contacting an implantable device structure with a collagen containing solution;

b) drying said collagen solution on said structure; and

c) embedding said collagen of said structure in a polymer matrix.

25. The method according to claim 24, wherein said collagen is embedded in said matrix using a reactive catechol at a pH sufficient to produce a reactive quinone.

26. The method according to claim 25, wherein said reactive catechol is a dicatechol.

27. The method according to claim 26, wherein said dicatechol is NDGA.

28. The method according to claim 24, wherein steps (a) and (b) of said method are repeated at least one time.

29. The method according to claim 24, wherein steps (a) and (b) of said method are repeated a plurality of times.

30. The method according to claim 24, wherein said drying step is freeze-drying.

31. The method according to claim 24, wherein said collagen embedded in said matrix is subsequently freeze-dried.

32. The method according to claim 24, wherein said collagen containing solution of step (a) comprises about 1% (w/v) collagen.

33. The method according to claim 24, wherein said collagen scaffold comprises open pores of about 10 μ

m to about 200 μ

m in diameter (mean).

34. The method according to claim 33, wherein the mean pore size of the collagen scaffold is about 60 μ

m or less in diameter.

35. The method according to claim 33, wherein the mean pore size of the collagen scaffold is between 40 μ

m and 80 μ

m in diameter.

36. A device having enhanced biocompatibility for implantation into the body or tissue of a person or animal, wherein said device comprises a biocompatible collagen scaffold or coating embedded within a polymer matrix.

37. The device according to claim 36, wherein said scaffold and/or coating is treated with a cross-linking compound comprising a reactive catechol at a pH sufficient to produce a reactive quinone.

38. The device according to claim 37, wherein said reactive catechol is a di-catechol.

39. The device according to claim 36, wherein said collagen scaffold and/or coating is embedded in a nordihydroguaiaretic acid (NDGA) bisquinone polymer matrix.

40. The device according to claim 36, wherein said device is a sensor.

41. The device according to claim 36, wherein said device is a glucose sensor.

42. The device according to claim 36, wherein said device comprises an epoxy coating underneath said collagen scaffold and/or coating.

43. The device according to claim 42, wherein said epoxy coating is an epoxy-polyurethane coating.

44. The device according to claim 36, wherein said scaffold comprises open pores of about 10 μ

m to about 200 μ

m in diameter (mean).

45. The device according to claim 44, wherein the mean pore size of said collagen scaffold is about 60 μ

m or less in diameter.

46. The device according to claim 44, wherein the mean pore size of said collagen scaffold is between about 40 μ

m and about 80 μ

m in diameter.

47. The device according to claim 36, wherein said scaffold comprises an antimicrobial, anti-inflammatory, and/or angiogenic compound, drug or growth factor.