Tissue-equivalent and method for preparation thereof

• US 4,485,096 A
• Filed: 05/26/1982
• Issued: 11/27/1984
• Est. Priority Date: 02/26/1982
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Bell, Eugene
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US06/381,978
• Time in Patent Office: 916 Days
• Field of Search: 424/95, 424/177, 435/240
• US Class Current: 424/532
• CPC Class Codes: A61F 2/00 Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents as cosmetic articles, see the relevant subclasses, e.g. wigs, hair pieces, A41G3/00, A41G5/00; artificial nails A45D31/00; dental prostheses A61C13/00; materials for prostheses A61L27/00; artificial hearts A61M60/00; artificial kidneys A61M1/14
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• 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 27/24 Collagen
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/365 Bones
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: Y10S 623/915 Method or apparatus for preparing biological material
• CPC Class Codes: Y10S 623/917 Collagen

Abstract

A tissue-equivalent, useful in the treatment of burns or other skin wounds and in the fabrication of prostheses, is disclosed which is prepared from a hydrated collagen lattice contracted by a contractile agent, such as fibroblast cells or blood platelets, to form tissue-equivalent. In one embodiment, a skin-equivalent can be fabricated by growing a layer of keratinocyte cells thereon. Both the keratinocyte cells and contractile agent may be derived from the potential recipient of the skin-equivalent.

Claims

1. A method of producing a tissue-equivalent, comprising:

a. combining a collagen solution with a contractile agent under conditions to form a gel mixture having said contractile agent dispersed within said gel mixture; and

then

b. maintaining the gel mixture prepared in step (a) under conditions which permit the contraction of said gel mixture to form a tissue-equivalent.

2. A method of claim 1 additionally including adding living tissue cells into or onto said tissue-equivalent.

3. A method of claim 1 or 2 wherein said contractile agent comprises fibroblast cells.

4. A method of claim 1 or 2 wherein said contractile agent comprises blood platelets.

5. A method of claim 1 or 2 wherein said contractile agent comprises smooth muscle cells.

6. A method of claim 1 or 2 wherein said contractile agent comprises striated muscle cells.

7. A method of claim, 1 or 2 wherein said contractile agent comprises heart muscle cells.

8. A tissue-equivalent formed according to the method of claim 1.

9. A tissue-equivalent formed according to the method of claim 2.

10. A method of preparing a living tissue-equivalent, comprising:

a. forming an acidic solution of collagen;

b. combining contractile cells and nutrient medium with said acidic solution of collagen;

c. raising the pH of said solution of collagen to a level sufficient to precipitate collagen fibrils into a hydrated collagen lattice containing said contractile cells; and

d. maintaining said lattice and said contractile cells under conditions sufficient for said cells to contract said collagen lattice thereby forming a living tissue-equivalent.

11. A method of claim 10 wherein steps b and c are done simultaneously.

12. A living tissue-equivalent formed by the method of claim 11.

13. A method of forming skin-equivalent, comprising:

a. forming a hydrated collagen lattice incorporating a living cellular contractile agent therein;

b. maintaining said lattice and said contractile agent under conditions sufficient for said agent to contract said collagen lattice to form living dermal-equivalent;

c. plating keratinocyte cells upon said dermal-equivalent; and

d. maintaining said dermal equivalent under conditions sufficient for growth of said living cellular contractile agent and said keratinocyte cells to thereby produce a skin-equivalent.

14. A skin-equivalent, comprising:

a. a hydrated collagen lattice contracted with a contractile agent; and

b. keratinocyte cells supported upon said contracted hydrated collagen lattice.

15. A method of treating a wound to the skin of a donor, comprising:

a. culturing fibroblast cells, in vitro, said fibroblast cells being derived from the donor;

b. forming a hydrated collagen lattice incorpotating said cultured fibroblast cells and maintaining said lattice and said cells under conditions whereby said fibroblast cells attach to said collagen lattice and contract it into a living tissue-equivalent; and

c. transplanting said living tissue-equivalent as a graft at the wound site of said donor.

16. A method of claim 15 additionally including growing a layer of keratinocytes upon said living tissue-equivalent prior to transplanting it.

17. A method of forming a biocompatible prosthesis for a potential recipient, comprising:

a. forming a hydrated collagen lattice incorporating a contractile agent obtained from said potential recipient; and

b. maintaining said lattice and contractile agent under conditions sufficient to contract the hydrated collagen lattice into biocompatible prosthesis.

20. A method of claim 17 or claim 19 wherein said contractile agent comprises fibroblast cells.

21. A method of claim 17 or claim 19 wherein said contractile agent comprises blood platelets.

22. A method of claim 17 or claim 19 wherein said contractile agent comprises smooth muscle cells.

23. A method of claim 17 or claim 19 wherein said contractile agent comprises striated muscle cells.

24. A method of claim 17 or claim 19 wherein said contractile agent comprises heart muscle cells.

18. A method of forming a biocompatible prosthesis for a potential recipient, comprising:

a. forming a hydrated collagen lattice incorporating a contractile agent obtained from a donor other than said potential recipient; and

b. maintaining said lattice and contractile agent under conditions sufficient for the agent to contract the hydrated collagen lattice into a biocompatible prosthesis.

19. A method of claim 18 wherein said contractile agent comprises fibroblast cells maintained under conditions which eliminate immune response in said potential recipient.

25. An organ-equivalent, comprising:

a. a hydrated collagen lattice contracted with fibroblast cells incorporated therein; and

b. living organ cells thereon or therein.

26. An organ-equivalent of claim 25 wherein said organ cells comprise heart cells.

27. An organ-equivalent of claim 25 wherein said organ cells comprise liver cells.

28. A gland-equivalent, comprising:

a. a hydrated collagen lattice contracted with fibroblast cells incorporated therein; and

b. living glandular cells thereon or therein.

29. A gland-equivalent of claim 28 wherein said glandular cells comprise insulin-producing pancreatic cells.