Methods of making expandable foam-like biomaterials
View Patent ↗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.
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.
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.
23. The biomaterial of claim 22 , which is made by the method of claim 2 .
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.