Enhanced Submucosal Tissue Graft Constructs

• US 20110165126A1
• Filed: 08/09/2010
• Published: 07/07/2011
• Est. Priority Date: 02/10/1995
• Status: Abandoned Application

• Current Assignee: Clarian Health Partners, Inc., Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: Clarian Health Partners, Inc., Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Boder, George B., Voytik-Harbin, Sherry, Lindberg, Kristina, Badylak, Stephen F.
• Application Number:
  US12/852,897
• Publication Number:
  US 20110165126A1
• Time in Patent Office: Days
• US Class Current: 424/93.2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/38 Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3629 Intestinal tissue, e.g. small intestinal submucosa
• CPC Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• 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 27/3808 Endothelial cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2500/32 Amino acids
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2533/92 Amnion; Decellularised dermis or mucosa
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: C12N 5/0679 Cells of the gastro-intestinal tract

Abstract

An improved tissue graft construct comprising submucosa of a warm-blooded vertebrate and a preselected group of eukaryotic cells are described. The improved tissue graft constructs can be used in accordance with the present invention to enhance the repair of damaged or diseased tissues in vivo.

Claims

1. An improved tissue graft construct comprising

vertebrate submucosa delaminated from both the external smooth muscle layers and the luminal portions of the tunica mucosa and

added primary epithelial cells.

2. The improved tissue graft construct of claim 1 wherein the vertebrate submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue.

3. The improved tissue graft construct of claim 1 wherein the primary epithelial cells are selected from the group consisting of primary gingiva epithelial cells and primary esophageal epithelial cells.

4. The improved tissue graft construct of claim 2, wherein the submucosa is fluidized submucosa.

5. The improved tissue graft construct of claim 4, wherein the fluidized submucosa comprises submucosa digested with an enzyme for a period of time sufficient to solubilize the submucosa.

6. A composition for the repair of articular cartilage defects, said composition comprising

tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue and

added primary chondrocyte cells.

7. The composition of claim 6, wherein the submucosal tissue is fluidized submucosal tissue.

8. The composition of claim 7, wherein the fluidized submucosal tissue comprises submucosal tissue digested with an enzyme for a period of time sufficient to solubilize the tissue.

9. A method for enhancing the capabilities of a vertebrate submucosa graft construct to repair articular cartilage defects, said method comprising the step of seeding the vertebrate submucosa graft construct with chondrocytes prior to implanting or injecting the vertebrate submucosa graft construct into a host.

10. The method of claim 9 further comprising the step of subjecting the seeded vertebrate submucosa graft construct to conditions conducive to the proliferation of the cells prior to implanting or injecting the vertebrate submucosa graft material into the host.

11. The method of claim 10 wherein the vertebrate submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue.

12. A method for enhancing the capabilities of a vertebrate submucosa graft construct to repair periodontal defects, said method comprising the step of seeding the vertebrate submucosa graft construct with primary gingiva epithelial cells prior to implanting or injecting the vertebrate submucosa graft construct into a host.

13. The method of claim 12 further comprising the step of subjecting the seeded vertebrate submucosa graft construct to conditions conducive to the proliferation of the cells prior to implanting or injecting the vertebrate submucosa graft material into the host.

14. The method of claim 12 wherein the vertebrate submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue.

15. An improved tissue graft construct comprising

vertebrate submucosa delaminated from both the external smooth muscle layers and the luminal portions of the tunica mucosa and

added primary cells.

16. The improved tissue graft construct of claim 15 wherein the vertebrate submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue.

17. The improved tissue graft construct of claim 15 wherein the primary cells are selected from the group consisting of endothelial cells, keratinocytes, chondrocytes, epithelial cells and mesenchymal cells.

18. The improved tissue graft construct of claim 16 wherein the submucosa is fluidized submucosa.

19. The improved tissue graft construct of claim 18 wherein the fluidized submucosa comprises submucosa digested with an enzyme for a period of time sufficient to solubilize the submucosa.

20. An improved tissue graft construct comprising

tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue, and

a population of cells selected from the group consisting of endothelial cells, keratinocytes and mesenchymal cells.

21. The improved tissue graft construct of claim 20 wherein the preselected cell type comprises cells that have been genetically modified.

22. The improved tissue graft construct of claim 20 wherein the submucosa tissue is fluidized submucosal tissue.

23. The improved tissue graft construct of claim 21 wherein the fluidized submucosal tissue comprises submucosal tissue digested with an enzyme for a period of time sufficient to solubilize the tissue.

24. A method for enhancing the capabilities of a submucosa graft construct to repair epithelial defects, said method comprising the step of seeding the submucosa with primary epithelial cells prior to implanting or injecting the graft construct into a host.

25. The method of claim 24 further comprising the step of subjecting the seeded graft construct to conditions conducive to the proliferation of the cells prior to injecting the graft material into the host.

26. The method of claim 24 wherein the submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue.