Self-supporting, shaped, three-dimensional biopolymeric materials and methods

• US 6,921,412 B1
• Filed: 05/12/2000
• Issued: 07/26/2005
• Est. Priority Date: 05/18/1999
• Status: Expired due to Fees

• Current Assignee: Cryolife Incorporated
• Original Assignee: Cryolife Incorporated
• Inventors: Trygstad, Aaron J., Yuksel, K. Umit, Black, Kirby S.
• Primary Examiner(s): Izaguirre, Ismael
• Application Number:
  US09/570,600
• Time in Patent Office: 1,901 Days
• Field of Search: 606/213, 606/214
• US Class Current: 606/213
• CPC Class Codes: A61L 24/0089 containing inorganic fillers not covered by groups A61L24/0078 or A61L24/0084
• CPC Class Codes: A61L 24/10 Polypeptides; Proteins A61L24/043 takes precedence

Abstract

Self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymeric materials that may be implanted in vivo, and methods of making such materials are disclosed. The biopolymeric materials most preferably include reinforcing media, such as biocompatible fibrous or particulate materials. In use, the preformed, shaped biopolymeric materials may be applied to tissue in need of repair and then sealed around its edges with a liquid bioadhesive. In such a manner, repaired tissue which is capable of withstanding physiological pressures may be provided.

Claims

1. A biomaterial structure which includes a biopolymeric member consisting of a pre-formed, self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymeric material.

2. The biomaterial structure of claim 1, which further includes a fibrous and/or particulate reinforcing medium adhered to said biopolymeric member.

3. The biomaterial structure of claim 2, wherein said fibrous reinforcing medium includes natural or synthetic fibers.

4. The biomaterial structure of claim 2, wherein said fibrous reinforcing medium includes a fabric formed of natural or synthetic fibers.

5. The biomaterial structure of claim 4, wherein the fabric is a woven fabric.

6. The biomaterial structure of claim 4, wherein the fabric is nonwoven.

8. The biomaterial structure of claim 1 or 7, wherein said biopolymeric member is porous.

7. A biomaterial structure which includes:

(i) a biopolymeric member consisting of a pre-formed, self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymeric material;

(ii) a particulate reinforcing medium adhered to said biopolymeric member, said particulate reinforcing medium having a nominal particle size of between about 1 μ

m to about 7 mm, and optionally

(iii) a fibrous reinforcing medium.

9. A biomaterial structure which includes:

(i) a biopolymeric member consisting of a pre-formed, self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymer which is the cross-linked reaction product of human or animal-derived protein material and a di- or polyaldehyde, and

(ii) a fibrous and/or particulate reinforcing medium embedded in said biopolymeric member.

10. The biomaterial structure of claim 9, wherein said fibrous reinforcing medium includes natural or synthetic fibers.

11. The biomaterial structure of claim 10, wherein said fibrous reinforcing medium includes a fabric formed of natural or synthetic fibers.

12. The biomaterial structure of claim 11, wherein the fabric is a woven fabric.

13. The biomaterial structure of claim 11, wherein the fabric is nonwoven.

14. A biomaterial structure which includes:

(i) a biopolymeric member consisting of a pre-formed, self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymer, and

(ii) a particulate reinforcing medium embedded within said biopolymeric member, wherein the particulate reinforcing medium has a nominal particle size of between about 1 μ

m to about 7 mm.

15. The biomaterial structure of claim 14, wherein said biopolymer is the cross-linked reaction product of human or animal-derived protein material and a di- or polyaldehyde.

16. The biomaterial structure of claim 9 or 15, wherein the protein is bovine or human serum albumin or hemoglobin.

17. The biomaterial structure of claim 16, wherein the aldehyde is glutaraldehyde.

18. A method of making a biomaterial structure comprising forming a biopolymeric member which consists of a self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymeric material, and embedding within said biopolymeric material a fibrous and/or particulate reinforcing medium.

19. The method of claim 18, which includes placing the fibrous and/or particulate reinforcing material onto a casting surface, and then casting the biopolymeric material as a liquid onto the casting surface to form the bioplymeric member as a sheet of reinforced biomaterial.

20. The method of claim 19, which includes moving a doctor blade over the mass of liquid biopolymeric material to achieve a predetermined sheet thickness.

21. The method of claim 19, which includes forming the sheet of reinforced biomaterial into a generally conically or cylindrically shaped structure.

22. The method of claim 21, wherein said step of forming the sheet of reinforced biomaterial into a generally conically or cylindrically shaped structure includes overlapping edge portions of the sheet, and fixing said overlapped edge portions to one another.

23. The method of claim 22, wherein said step of forming the sheet of reinforced biomaterial into a generally conically or cylindrically shaped structure includes applying a liquid bioadhesive to said overlapped edges.

24. The method of claim 18, wherein said reinforcing medium is particulate, and wherein the method further comprises dissolving the particulate reinforcing medium to obtain a porous biopolymeric member.

25. The method of claim 18, which further comprises subjecting the biopolymeric member to an aftertreatment sufficient to obtain desired physical and/or chemical properties.

26. The method of claim 25, wherein the aftertreatment includes bringing the biopolmeric member into contact with a treatment liquid.

27. The method of claim 26, wherein the treatment liquid includes water or an organic liquid.

28. The method of claim 27, wherein the organic liquid includes alcohol, urea or glutaraldehyde solutions.

29. The method of claim 26, wherein the treatment liquid includes an aqueous solution of sodium chloride.

30. The method of claim 29, wherein the sodium chloride solution is between about 0.5 molar to 5.0 molar.

31. A method of making a porous biomaterial structure comprising the steps of (i) forming a biopolymeric member which consists of a self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymeric material, (ii) incorporating a dissolvable particulate medium within the biopolymeric material, and thereafter (iii) dissolving the particulate medium from the biopolymeric material to thereby render the biomaterial structure porous.

32. The method of claim 31, wherein said step of dissolving the particulate medium from the biopolymeric material includes bringing the biomaterial structure into contact with a liquid solvent for said particulate medium for a time sufficient to dissolve an amount of said particulate material to render the biomaterial structure porous.

33. The method of claim 32, wherein the particulate material includes calcium carbonate.

34. The method of claim 33, wherein the calcium carbonate is present in an amount between about 2 wt. % to about 65 wt. %.

35. The method of any one of claims 31-34, which comprises bringing the biomaterial structure in which the particulate material is dispersed into contact with an acid.

36. The method of claim 35, wherein the acid is hydrochloric acid.

37. A porous biomaterial made according to the method of claim 31.

38. A method of repairing damaged human or animal tissue in vivo, which comprises positioning a biomaterial structure which includes a biopolymeric member consisting of a preformed, self-supporting, three-dimensionally shaped biopolymer onto a tissue site in need of repair, and thereafter sealing edges of the biomaterial structure to the tissue by application of a bioadhesive.

39. The method of claim 38, wherein the biomaterial structure is in the form of a sheet, ring, tube, cylinder and/or cone.

40. The method of claim 38, wherein the biomaterial structure includes a fibrous or particulate reinforcing medium.

41. The method of claim 40, wherein the biomaterial structure is in the form of a sheet.

42. The method of claim 40, wherein the biomaterial structure is in the form of a tube, cylinder or cone.

43. The method of claim 40, wherein the biomaterial structure is in the form of a tube having a substantially constant outside diameter, and a variably stepped inside diameter.

44. The method of claim 40, further comprising placing at least one tack suture into the biomaterial structure to initially positionally fix the biomaterial structure to the tissue in need of repair.

45. The method of claim 38, wherein the biomaterial structure is porous.

46. A biomaterial structure which includes a biopolymeric member consisting of a pre-formed, self-supporting, shaped, three-dimensional cross-linked proteinaceous biopolymeric material which is the cross-linked reaction product of human or animal-derived protein material and a di- or polyaldehyde.

47. The biomaterial structure of claim 46, wherein the protein is bovine or human serum albumin or hemoglobin.

48. The biomaterial structure of claim 46, wherein the aldehyde is glutaraldehyde.

49. The biomaterial structure of claim 46, which includes a fibrous and/or particulate reinforcing medium adhered to said biopolymeric member.

50. The biomaterial structure of claim 49, wherein said fibrous reinforcing medium includes natural or synthetic fibers.

51. The biomaterial structure of claim 49, wherein said fibrous reinforcing medium includes a fabric formed of natural or synthetic fibers.

52. The biomaterial structure of claim 51, wherein the fabric is a woven fabric.

53. The biomaterial structure of claim 51, wherein the fabric is nonwoven.

54. The biomaterial structure of claim 49, wherein the particulate reinforcing medium has a nominal particle size of between about 1 μ

m to about 7 mm.

55. The biomaterial structure of claim 46, wherein said biopolymeric member is porous.

56. A method of making a reinforced biomaterial which comprises (i) embedding a fibrous and/or particulate reinforcing medium within a mass of liquid cross-linkable biopolymeric material, thereafter (ii) allowing the biopolymeric material to cross-link and thereby cure to form a sheet of self-supporting, fibrous and/or particulate reinforced biomaterial, (iii) forming the sheet of reinforced biomaterial into a generally conically or cylindrically shaped structure by overlapping edge portions of the sheet and fixing said overlapped edge portions to one another.

57. The method of claim 56, wherein step (iii) includes applying a liquid bioadhesive to said overlapped edges.