Methods of making expandable foam-like biomaterials

• US 8,057,818 B2
• Filed: 01/26/2005
• Issued: 11/15/2011
• Est. Priority Date: 11/07/2000
• Status: Active Grant

• Current Assignee: Cryolife Incorporated
• Original Assignee: Cryolife Incorporated
• Inventors: Yüksel, K. Umit, Bird, Ana T., Black, Kirby S.
• Primary Examiner(s): Woodward; Cherie M
• Assistant Examiner(s): Kassa; Tigabu
• Application Number:
  US11/042,181
• Publication Number:
  US 20050158364A1
• Time in Patent Office: 2,484 Days
• Field of Search: None
• US Class Current: 424/444
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges

Abstract

Liquid, injectable, aqueous solutions are transformed in situ to an expandable foam-like, space filling, and adherent biomaterial. Preferably, the foam-like biomaterial is the reaction product of a two-part liquid system to achieve the in situ formation thereof. The liquid system is generally comprised of a protein solution and a cross linker solution which may either be premixed and then applied to a site in need of the biomaterial, or simultaneously mixed and delivered through an in-line mixing/dispensing tip directly to the site. In especially preferred embodiments, an expandable foam-like biomaterial includes the reaction product of human or animal-derived protein material and a di- or polyaldehyde in the presence of a bicarbonate and an acidic titrant amounts sufficient to impart a cellular foam structure to the material.

Claims

1. A method of making a biopolymeric material having a cellular foam structure comprising:

combining a proteinaceous pre-polymeric liquid material and a cross linker solution to produce a mixture, wherein the proteinaceous pre-polymeric liquid material comprises a water soluble or plasma protein;

introducing or producing a gaseous blowing agent into the proteinaceous pre-polymeric liquid material or the mixture; and

allowing the mixture to cross-link and solidify simultaneously with the introduction or production of the gaseous blowing agent to thereby form the biopolymeric material having a cellular foam structure.

2. The method of claim 1, wherein the proteinaceous pre-polymeric liquid material comprises an aqueous solution of human or animal-derived protein material and the cross linker solution comprises an aqueous solution of a di- or polyaldehyde.

3. The method of claim 2, wherein the aqueous solution of human or animal-derived protein material further comprises a bicarbonate and the aqueous solution of said di- or polyaldehyde further comprises an acidic titrant.

4. The method of claim 2 or 3, wherein the biopolymeric material has a volume which is greater than combined volumes of the aqueous solutions.

5. The method of claim 2, wherein the aqueous solution of human or animal-derived protein material is neutral or slightly alkaline.

6. The method of claim 5, wherein the aqueous solution of di- or polyaldehyde is acidic.

7. The method of claim 2, wherein the human or animal-derived protein material comprises albumin.

8. The method of claim 7, wherein the human or animal-derived protein material comprises serum albumin.

9. The method of claim 2, wherein the aqueous solution of a di- or polyaldehyde comprises glutaraldehyde.

10. The method of claim 1, wherein the biopolymeric material is adhesive to human or animal tissue.

11. The method of claim 1, wherein the step of combining comprises:

expelling the proteinaceous pre-polymeric liquid material from a first chamber and expelling the cross linker solution from a second chamber, and

passing the expelled materials into a mixing tip comprising static mixing elements that cause the proteinaceous pre-polymeric liquid material and the cross linker solution to combine to form the mixture.

23. The biomaterial of claim 22, which is made by the method of claim 2.

12. A method of making a biopolymeric material having a cellular foam structure comprising:

combining a proteinaceous pre-polymeric liquid material and an aqueous solution of a di- or polyaldehyde to produce a mixture;

introducing or producing a gaseous blowing agent into the mixture; and

then allowing the mixture to solidify to thereby form the biopolymeric material having a cellular foam structure, wherein the biopolymeric material has a volume which is greater than the sum of the volumes of the proteinaceous pre-polymeric liquid material and aqueous solution.

13. The method of claim 12, wherein the biopolymeric material is adhesive to human or animal tissue.

14. The method of claim 12, wherein the proteinaceous pre-polymeric liquid material comprises human or bovine serum albumin.

15. The method of claim 12, wherein the aqueous solution of a di- or polyaldehyde comprises glutaraldehyde.

16. A method of making a biopolymeric material having a cellular foam structure comprising:

preparing a two-part mixture which comprises a Part A and a Part B, wherein the Part A includes an aqueous solution of a human- or animal-derived protein material and a bicarbonate compound, and the Part B includes an aqueous solution of a di- or polyaldehyde and a titrant, and wherein the bicarbonate compound and the titrant react to evolve a gas into the two-part mixture; and

allowing the two-part mixture to react and solidify, thereby forming a biopolymeric material having a cellular foam structure which has a volume that is greater than the sum of the volumes of the aqueous solutions of Parts A and B.

17. The method of claim 16, wherein the bicarbonate compound comprises sodium bicarbonate, potassium bicarbonate, or ammonium bicarbonate.

18. The method of claim 16, wherein the titrant comprises phosphoric acid, sulfuric acid, hydrochloric acid, citric acid, or acetic acid.

19. The method of claim 16, wherein the human- or animal-derived protein material comprises albumin.

20. The method of claim 19, wherein the albumin is human or bovine serum albumin.

21. The method of claim 16, wherein the di- or polyaldehyde comprises a glutaraldehyde.

22. A foam biomaterial comprising:

a human- or animal-derived plasma or water-soluble protein material crosslinked with a di- or polyaldehyde, wherein the di- or polyaldehyde comprises glutaraldehyde, wherein the biomaterial comprises a solid cellular foam structure comprising albumin, and wherein the foam biomaterial is sterilized.

24. The biomaterial of claim 22, wherein the albumin comprises human or bovine serum albumin.

25. The biomaterial of claim 22, wherein the cellular foam structure comprises both open and closed cells.

26. The biomaterial of claim 22, which is adhesive to human or animal tissue.