Biomaterial derived from vertebrate liver tissue

• US 6,379,710 B1
• Filed: 06/10/1999
• Issued: 04/30/2002
• Est. Priority Date: 12/10/1996
• Status: Expired due to Term

• Current Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Badylak, Stephen F.
• Primary Examiner(s): Witz, Jean C.
• Application Number:
  US09/319,781
• Time in Patent Office: 1,055 Days
• Field of Search: 424/553
• US Class Current: 424/553
• 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: A61K 35/407 Liver; Hepatocytes
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

A tissue graft composition comprising liver basement membrane is described. The graft composition can be implanted to replace or induce the repair of damaged or diseased tissues.

Claims

1. A composition comprising liver basement membrane of a warm-blooded vertebrate, wherein the liver basement membrane is substantially free of cells of said warm-blooded vertebrate and the liver basement membrane is retained in its natural three dimensional shape.

2. A composition prepared from liver tissue of a warm-blooded vertebrate, wherein said composition is useful as a non-immunogenic tissue graft capable of inducing endogenous tissue growth when implanted in warm-blooded vertebrates, said composition comprising an extracellular matrix consisting essentially of liver basement membrane retained in its natural three dimensional shape and devoid of endogenous cells associated with said liver tissue.

3. A method for inducing the formation of endogenous connective tissue at a site in need of endogenous tissue growth in a warm blooded vertebrate, said method comprising implanting a graft composition comprising an extracellular matrix consisting essentially of basement membrane of liver tissue of a warm-blooded vertebrate in an amount effective to induce endogenous tissue growth at the site the graft composition is administered, said liver basement membrane being devoid of endogenous cells associated with said liver tissue.

4. The method of claim 3, wherein the graft composition is fluidized and is administered by injection into the warm-blooded vertebrate.

5. The method of claim 3, wherein the graft composition is administered by surgically implanting the composition into the warm-blooded vertebrate.

6. A method for preparing a tissue graft composition comprising extracellular matrix components of vertebrate liver tissue, said method comprising the steps of

treating warm-blooded vertebrate liver tissue having both cellular and extracellular components with a cell dissociation solution for a period of time sufficient to release the cellular components of the liver tissue from the extracellular matrix components without substantial disruption of the extracellular matrix components, and

separating the extracellular matrix components from the cellular components wherein said extracellular components are used to form the tissue graft composition.

7. The method of claim 6 wherein the cell dissociation solution comprises a chaotropic agent.

8. The method of claim 6 wherein the cell dissociation solution comprises a protease.

9. The method of claim 6 wherein the cell dissociation solution compnses EDTA and trypsin.

10. The method of claim 6 wherein the liver tissue is sliced into sheets or strips of liver tissue before the liver tissue is treated with the dissociation solution.

11. The method of claim 10 where the liver tissue is sliced into sheets or strips having a thickness of up to abut 500 μ

.

14. The method of claim 6 further comprising the step of comminuting the extracellular matrix components to form a fluidized tissue graft composition.

15. The method of claim 14 further comprising the step of enzymatically digesting the extracellular matrix material to form a fluidized tissue graft composition.

16. The method of claim 14 further comprising the step of drying the fluidized tissue graft composition to the form of a dry powder.

17. The method of claim 15 further comprising the step of drying the fluidized tissue graft composition to the form of a dry powder.

12. A liver tissue derived composition for supporting the growth of a cell population, said composition comprising isolated liver basement membrane retained in its natural three dimensional shape and devoid of source liver tissue endogenous cells;

and

added nutrients to support the growth of said cell population in vitro.

13. A liver tissue derived composition for supporting the growth of a cell population, said composition comprising

culture-ware coated with a matrix consisting essentially of liver basement membrane devoid of source liver tissue endogenous cells.