Biodegradable, porous structures useful for growing living tissue, and methods of manufacture

• US 20030215946A1
• Filed: 12/05/2002
• Published: 11/20/2003
• Est. Priority Date: 12/06/2001
• Status: Active Grant

• Current Assignee: University of Washington, Georgia Tech Research Corporation (University System of Georgia)
• Original Assignee: University of Washington, Georgia Tech Research Corporation (University System of Georgia)
• Inventors: Ratner, Buddy D., Vogel, Viola, Nair, Prabha D., Nerem, Robert M.
• Granted Patent: US 7,105,580 B2
• Time in Patent Office: Days
• US Class Current: 435/395
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body

Abstract

In one aspect the present invention provides biodegradable, porous structures that each include a structural framework, wherein the structural framework includes: (a) a solidified mixture of polymer molecules and amino acid molecules, wherein at least some of the amino acid molecules are linked to other amino acid molecules within the framework; and (b) a multiplicity of interconnected spaces defined by the structural framework. In some embodiments, the porous structures of the invention are adapted to physically support the growth of living cells in vitro or in vivo, and can be used to grow living tissue and/or living organs. The present invention also provide methods for making the biodegradable, porous structures of the invention.

Claims

1. A porous structure comprising a structural framework, wherein said porous structure is biodegradable, and wherein said framework comprises:

(a) a solidified mixture of polymer molecules and amino acid molecules, wherein at least some of the amino acid molecules are linked to other amino acid molecules within said framework; and

(b) a multiplicity of interconnected spaces defined by the structural framework.

2. The porous structure of claim 1 wherein the porous structure is adapted to physically support the growth of living cells.

3. The porous structure of claim 1 wherein at least some of the polymer molecules are biodegradable.

4. The porous structure of claim 1 wherein none of the polymer molecules are biodegradable.

5. The porous structure of claim 1 wherein some of the polymer molecules are biodegradable and some of the polymer molecules are not biodegradable.

6. The porous structure of claim 1 wherein the polymer molecules comprise biodegradable polymer molecules selected from the group consisting of collagen, proteins, polysaccharide, fibrin, chitosan, poly(lactic acid), poly(glycolic acid), poly(lactic acid-glycolic acid copolymers), polyglycolides, aliphatic polyesters, poly(esteramides), polyamides, polyanhydrides, polyorthoesters, polyurethanes, and polyphosphazenes.

7. The porous structure of claim 1 wherein the polymer molecules comprise non-biodegradable polymer molecules selected from the group consisting of polyethylene glycol, polyethylenoxide, polyvinyl alcohol, polyethylene oxide-polypropylene oxide copolymer, polyvinyl pyrrolidone, polyhydroxy ethyl methacrylate, polysiloxanes, polycarbonates, and polyacrylates.

8. The porous structure of claim 1 wherein the amino acid molecules are selected from the group consisting of aspartic acid, isoleucine, threonine, leucine, serine, tyrosine, glutamic acid, phenylalanine, proline, histidine, glycine, lysine, alanine, arginine, cysteine, tryptophan, valine, glutamine, methionine, and asparagine.

9. The porous structure of claim 1 wherein some of the amino acid molecules within the structural framework are covalently linked to other amino acids within the structural framework.

10. The porous structure of claim 1 wherein the average diameter of the interconnected spaces is from 1 μ

m to 300 μ

m.

11. The porous structure of claim 1 wherein the average diameter of the interconnected spaces is from 1 μ

m to 100 μ

m.

12. The porous structure of claim 1 further comprising biologically active molecules attached to said structural framework.

13. The porous structure of claim 1 wherein the ratio of polymer molecules to amino acid molecules is at least 25:

75.

14. The porous structure of claim 1 wherein the ratio of polymer molecules to amino acid molecules is from 25:

75 to 100;

1.

15. A method of making a biodegradable, porous structure comprising a multiplicity of interconnected spaces defined by a structural framework, the method comprising the steps of:

(a) making an aphron from a population of molecules, wherein said population comprises molecules selected from the group consisting of (1) biodegradable polymer molecules, and (2) a mixture of amino acid molecules and polymer molecules;

(b) freezing the aphron in a mold to yield a frozen, porous, structure comprising a multiplicity of interconnected spaces defined by a structural framework; and

(c) lyophilizing the frozen, porous, structure to yield a lyophilized, biodegradable, porous structure comprising a multiplicity of interconnected spaces defined by a structural framework.

16. The method of claim 15 further comprising the step of covalently linking at least some of the amino acid molecules present in the lyophilized structure to other amino acid molecules present in the lyophilized structure.

17. The method of claim 15 wherein the biodegradable, porous structure is adapted to physically support the growth of living cells.

18. The method of claim 15 wherein the polymer molecules are selected from the group consisting of collagen, proteins, polysaccharide, fibrin, chitosan, poly(lactic acid), poly(glycolic acid), poly(lactic acid-glycolic acid copolymers), polyglycolides, aliphatic polyesters, poly(esteramides), polyamides, polyanhydrides, polyorthoesters, polyurethanes, and polyphosphazenes.

19. The method of claim 15 wherein the amino acid molecules are selected from the group consisting of aspartic acid, isoleucine, threonine, leucine, serine, tyrosine, glutamic acid, phenylalanine, proline, histidine, glycine, lysine, alanine, arginine, cysteine, tryptophan, valine, glutamine, methionine, and asparagine.

20. The method of claim 15 wherein the average diameter of the interconnected spaces is from 1 μ

m to 300 μ

m.

21. The method of claim 15 wherein the average diameter of the interconnected spaces is from 1 μ

m to 100 μ

m.

22. The method of claim 15 wherein the ratio of polymer molecules to amino acid molecules within the lyophilized, porous, structure is at least 25:

75.

23. The method of claim 15 wherein the ratio of polymer molecules to amino acid molecules within the lyophilized, porous, structure is from 25:

75 to 100;

1.

24. The method of claim 15 wherein the lyophilized, porous, structure further comprises biologically active molecules attached to said structural framework.

25. The method of claim 15 wherein the aphron is made from a population of molecules comprising a mixture of amino acid molecules and polymer molecules;

the aphron is frozen in a mold to yield a frozen, porous, structure that comprises a structural framework, wherein the framework comprises;

(1) a solidified mixture of polymer molecules and amino acid molecules, wherein at least some of the amino acid molecules are linked to other amino acid molecules; and

(2) a multiplicity of interconnected spaces defined by the structural framework.

26. A method for growing a living tissue or a living organ, the method comprising the steps of:

(a) introducing living cells into a biodegradable, porous structure, said structure comprising a structural framework, wherein the structural framework comprises;

(1) a solidified mixture of polymer molecules and amino acid molecules, wherein at least some amino acid molecules are linked to other amino acid molecules within the structural framework; and

(2) a multiplicity of interconnected spaces defined by the structural framework; and

(b) culturing the cells within the porous structure under conditions that promote formation of a living tissue or a living organ.

27. The method of claim 26 wherein said method is practiced in vitro.

28. The method of claim 26 wherein said method is practiced in vivo.