Biopolymer foams for use in tissue repair and reconstruction

• US 5,891,558 A
• Filed: 11/21/1996
• Issued: 04/06/1999
• Est. Priority Date: 11/22/1994
• Status: Expired due to Fees

• Current Assignee: TEI Biosciences, Inc. (Integra LifeSciences Holdings Corporation)
• Original Assignee: Tissue Engineering, Inc. (Integra LifeSciences Holdings Corporation)
• Inventors: Bell, Eugene, Fofonoff, Timothy W., Sioussat, Tracy M.
• Primary Examiner(s): Bell, James J.
• Assistant Examiner(s): Copenheaver, Blaine R
• Application Number:
  US08/754,818
• Time in Patent Office: 866 Days
• Field of Search: 428/305.5, 428/316.6, 428/317.9, 428/323, 428/218, 424/423, 424/425, 424/426, 623/1, 623/12, 623/15, 433/201.1, 442/370
• US Class Current: 428/218
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 2430/10 for reconstruction of tendons or ligaments
• CPC Class Codes: A61L 2430/12 for dental implants or prostheses
• CPC Class Codes: A61L 2430/28 for liver reconstruction
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3826 Muscle cells, e.g. smooth muscle cells
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/0068 : General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: Y10S 623/924 : Material characteristic
• CPC Class Codes: Y10T 428/24992 : Density or compression of components
• CPC Class Codes: Y10T 428/249954 : With chemically effective material or specified gas other than air, N, or carbon dioxide in void-containing component
• CPC Class Codes: Y10T 428/249979 : Specified thickness of void-containing component [absolute or relative] or numerical cell dimension
• CPC Class Codes: Y10T 428/249981 : Plural void-containing components
• CPC Class Codes: Y10T 428/249986 : Void-containing component contains also a solid fiber or solid particle
• CPC Class Codes: Y10T 428/249999 : Differentially filled foam, filled plural layers, or filled layer with coat of filling material
• CPC Class Codes: Y10T 428/25 : Web or sheet containing structurally defined element or component and including a second component containing structurally defined particles
• CPC Class Codes: Y10T 442/15 : Including a foam layer
• CPC Class Codes: Y10T 442/3325 : Including a foamed layer or component
• CPC Class Codes: Y10T 442/647 : Including a foamed layer or component

Abstract

Single and double density biopolymer foams, composite biopolymer foams including both single and double density foams, and methods of preparing these foams and composite foams are described. Also described are biocompatible constructs which include single or double density biopolymer foams and extracellular matrix particulates and methods of preparing these constructs. The foams, composite foams, and biocompatible constructs of the invention can be used in tissue repair and reconstruction.

Claims

1. A composite biopolymer foam comprising:

a double density biopolymer foam comprising a network of communicating microcompartments having biopolymer molecules and/or biopolymer filaments interspersed within the walls of the microcompartments, wherein the microcompartments;

have dimensions of length, width, and height, wherein two of the volume dimensions are substantially equal and the third is decreased by a factor of at least about ten compared to the other volume dimensions and range from about 1 μ

m to about 300 μ

m, and have an average wall thickness of less than about 10 μ

m; and

a second biopolymer in the form of a fiber-based reinforcing material or a foam.

2. The composite foam of claim 1, wherein the second biopolymer comprises a single density foam comprising a network of communicating microcompartments having biopolymer molecules and/or biopolymer filaments interspersed within the walls of the microcompartments, wherein the microcompartments:

have dimensions of length, width, and height, are substantially equal, and range from about 1 μ

m to about 300 μ

m, and have an average wall thickness of less than about 10 μ

m.

3. The composite foam of claim 2, wherein the single and double density biopolymer foams include or are conditioned with cells.

4. A skin dressing comprising the composite foam of claim 3, wherein the single density biopolymer foam is conditioned with human dermal fibroblasts and the double density biopolymer foam is conditioned with human keratinocytes such that a stratum corneum is formed.

5. The skin dressing of claim 4, wherein the single density and double density biopolymer foams containing cells are freeze-dried after cell conditioning.

6. The composite foam of claim 2, wherein the single density biopolymer foam includes or is conditioned with cells.

7. The composite foam of claim 1, wherein the double density biopolymer foam includes or is conditioned with cells.

8. The composite foam of claim 1, wherein the biopolymer in the double density biopolymer foam comprises collagen.

9. The composite foam of claim 1, wherein the biopolymer in the double density biopolymer foam or the second biopolymer is selected from the group consisting of collagen, alginic acid, polyvinyl alcohol, chondroitin sulfate, laminin, elastin, fibronectin, and fibrinogen.

10. The composite foam of claim 9, wherein the biopolymer in the double density biopolymer foam or the second biopolymer is collagen.

11. The composite foam of claim 10, wherein the collagen is fetal porcine collagen.

12. The composite foam of claim 10, wherein the collagen is polymerized.

13. The composite foam of claim 10, wherein the collagen is crosslinked.

14. The composite foam of claim 13, wherein the collagen is crosslinked through lysyl oxidase priming.

15. The composite foam of claim 1, wherein the biopolymer in the double density biopolymer foam or the second biopolymer comprises a mixture of at least two different biopolymers.

16. The composite foam of claim 1, further comprising extracellular matrix particulates.

17. The composite foam of claim 16, which is coated with extracellular matrix particulates.

18. The composite foam of claim 16, wherein the extracellular matrix particulates are dispersed in the double density biopolymer foam or in the second biopolymer.

19. The composite foam of claim 1, further comprising cells.

20. The composite foam of claim 1, wherein the second biopolymer comprises a double density biopolymer foam comprising a network of communicating microcompartments having biopolymer molecules and/or biopolymer filaments interspersed within the walls of the microcompartments, wherein the microcompartments:

have dimensions of length, width, and height, wherein two of the volume dimensions are substantially equal and the third is decreased by a factor of at least about ten compared to the other volume dimensions and range from about 1 μ

m to about 300 μ

m, and have an average wall thickness of less than about 10 μ

m.

21. The composite foam of claim 1, wherein the second biopolymer comprises a fiber-based reinforcing material.

22. The composite foam of claim 21, wherein the fiber-based reinforcing material comprises collagen.

23. The composite foam of claim 21, wherein the fiber-based reinforcing material comprises a biopolymer fiber.

24. The composite foam of claim 23, wherein the biopolymer fiber comprises collagen.

25. The composite foam of claim 23, wherein the biopolymer fiber is a braided biopolymer fiber.

26. A vascular prosthesis comprising the composite foam of claim 23, wherein the double density biopolymer foam is in the form of a tube.

27. The vascular prosthesis of claim 26, wherein the biopolymer fiber is wound around the tube.

28. The vascular prosthesis of claim 27, wherein a second double density biopolymer foam comprising a network of communicating microcompartments having biopolymer molecules and/or biopolymer filaments interspersed within the walls of the microcompartments, wherein the microcompartments:

have dimensions of length width, and height, wherein two of the volume dimensions are substantially equal and the third is decreased by a factor of at least about ten compared to the other volume dimensions and range from about 1 μ

m to about 300 μ

m, and have an average wall thickness of less than about 10 μ

m is cast around the biopolymer fiber.

29. The vascular prosthesis of claim 28, further comprising endothelial cells on its luminal surface and smooth muscle cells throughout and on its abluminal surface.

30. The vascular prosthesis of claim 29, wherein the tubular double density biopolymer foam containing the cells is freeze-dried after cell conditioning.

31. The vascular prosthesis of claim 30, wherein the tubular double density biopolymer foam further comprises a layer of adventitial cells on the smooth muscle cells.

32. The vascular prosthesis of claim 31, wherein the tubular double density biopolymer foam containing the cells is freeze-dried after cell conditioning.

33. The composite foam of claim 21, wherein the fiber-based reinforcing material comprises a fabric.

34. The composite foam of claim 33, wherein the fabric comprises a nonwoven fabric.

35. A vascular prosthesis comprising the composite biopolymer foam of claim 1, the composite foam being in the form of a tube.

36. A dental implant capable of promoting periodontal ligament repair and bone rebuilding comprising the composite biopolymer foam of claim 1 which is apron shaped.

37. The dental implant of claim 36, wherein the second biopolymer of the composite biopolymer foam is a double density biopolymer foam comprising a network of communicating microcompartments having biopolymer molecules and/or biopolymer filaments interspersed within the walls of the microcompartments, wherein the microcompartments:

have dimensions of length, width, and height, wherein two of the volume dimensions are substantially equal and the third is decreased by a factor of at least about ten compared to the other volume dimensions and range from about 1 μ

m to about 300 μ

m, and have an average wall thickness of less than about 10 μ

m.

38. The dental implant of claim 37, which includes an outpocketing capable of holding a bone rebuilding material.

39. The dental implant of claim 37, further comprising periodontal ligament cells.

40. The dental implant of claim 37, further comprising extracellular matrix particulates derived from dental tissue.