In vivo synthesis of connective tissues

• US 20050112173A1
• Filed: 09/14/2004
• Published: 05/26/2005
• Est. Priority Date: 09/19/2003
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Mao, Jeremy Jian
• Granted Patent: US 7,375,077 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• 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 27/3843 Connective tissue
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/066 Tenocytes; Tendons, Ligaments

Abstract

The in vivo synthesis of connective tissue by fibroblast or fibroblast precursor cells ensconced within a biocompatible scaffold is disclosed. The cells are preferably present in a biocompatible scaffold such as gelatin and placed between two other biocompatible scaffolds such as collagen sponges soaked with a collagenic amount of a member of the TGF-β family of proteins. This composition is then implanted in a host to produce cranial sutures, periodontal ligament or other fibrous tissue structures in vivo.

Claims

1. A composition construct that comprises precursor cells that are seeded in a biocompatible scaffold.

2. The composition according to claim 1 wherein said precursor cells are fibroblast-like cells, stem cells or a mixture thereof.

3. The composition according to claim 1 wherein the biocompatible scaffold is comprised of a plurality of layers.

4. The composition according to claim 3 wherein the biocompatible scaffold has multiple layers.

5. The composition according to claim 4 wherein the biocompatible scaffold is comprised of a gelatin layer that is sandwiched between two collagen sponge layers or one collagen layer sandwiched between two gelatin layers.

6. The composition according to claim 5 wherein one or both collagen sponge layers contains growth factor protein(s).

7. The composition according to claim 6 wherein said growth factor is a member of the TGF-β

family of proteins.

18. A method of producing connective tissue comprising the steps:

(a) providing a composition according to claim 1;

and

(b) implanting the composition into an animal host.

19. The method of claim 18 wherein the connective tissue is a cranial suture or periodontal ligament.

8. A composition that comprises precursor cells that are seeded in a biocompatible scaffold comprised of a gelatin layer sandwiched between two collagen sponge layers, wherein one or both collagen sponge layers contains an effective mount of a growth factor protein that is a member of the TGF-β

family of proteins.

9. The composition according to claim 8 wherein both collagen sponge layers contain rhBMP-2 as the member of the TGF-β

family of proteins.

10. The composition according to claim 9 wherein said precursor cells are autologous fibroblastic cells or fibroblast-like cells.

11. The composition according to claim 8 wherein said precursor cells are stem cells.

12. The composition according to claim 11 wherein said stem cells are adult stem cells.

13. The composition according to claim 12 wherein said adult stem cells are adult mesenchymal stem cells.

14. The composition according to claim 11 that also includes an effective amount of a osteogenic agent.

15. The composition according to claim 8 wherein the biocompatible scaffold comprises a material selected from the group consisting of polylactic acid, polyglycolic acid, polyelthylene glycol, polyethylene glycol and mixtures thereof.

16. The composition according to claim 8 wherein the biocompatible scaffold comprises a natural material selected from the group consisting of alginate, chitosan, coral, agarose, fibrin, collagen, gelatin, bone, silicone, cartilage, hydroxyapatite, calcium phosphate, and mixtures thereof.

17. A composition that comprises fibroblastic cells that are seeded in a biocompatible scaffold comprised of a gelatin layer that is sandwiched between two collagen sponge layers, wherein one or both collagen sponge layers contains a collagenic amount of a member of the TGF-β

family of proteins.