Stabilization of implantable bioprosthetic tissue

• US 6,824,970 B2
• Filed: 05/15/2002
• Issued: 11/30/2004
• Est. Priority Date: 02/09/2000
• Status: Expired due to Fees

• Current Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation)
• Original Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation)
• Inventors: Vyavahare, Narendra, Levy, Robert J., Alferiev, Ivan
• Primary Examiner(s): Saucier, Sandra E.
• Application Number:
  US10/145,038
• Publication Number:
  US 20020172706A1
• Time in Patent Office: 930 Days
• Field of Search: 435/1.1, 600/36, 623/901, 623/915, 623/920, 623/925, 623/2.13, 623/1.1
• US Class Current: 435/1.1
• 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 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062

Abstract

The invention relates to implantable bioprostheses (e.g. implantable biological tissues) and to compositions and methods for stabilizing them. Implantable bioprostheses stabilized as described herein exhibit improved mechanical properties and reduced post-implantation calcification. The implantable bioprosthesis is made by contacting a bioprosthesis (e.g. a tissue obtained from an animal or an article comprising a tissue and a synthetic material) with a polyepoxy amine compound.

Claims

1. A method of manufacturing an implantable bioprosthesis, the method comprising:

providing the bioprosthesis comprising proteins;

providing a first stabilizing reagent which is a polyepoxy amine compound; and

contacting the bioprosthesis and the polyepoxy amine compound, whereby the bioprosthesis is manufactured.

2. An implantable bioprosthesis manufactured by the method of claim 1, wherein the bioprosthesis comprises the proteins cross-linked by contacting the bioprosthesis with the polyepoxy amine compound.

3. The implantable bioprosthesis of claim 2, wherein the bioprosthesis is contacted with the polyepoxy amine compound in an aqueous liquid having a pH of about 6 to 10.

4. The implantable bioprosthesis of claim 2, wherein the proteins are cross-linked by contacting the bioprosthesis with the polyepoxy amine compound in an aqueous liquid having a pH of about 7 to 10.

5. The implantable bioprosthesis of claim 2, wherein the proteins are cross-linked by contacting the bioprosthesis with the polyepoxy amine compound in an aqueous liquid having a pH of about 7.0 to 7.4.

6. The implantable bioprosthesis of claim 2, wherein the polyepoxy amine compound is triglycidyl amine.

7. The implantable bioprosthesis of claim 2, wherein the proteins are cross-linked by contacting the polyepoxy amine compound with moieties of the proteins which are members independently selected from the group consisting of a methylthio moiety, a primary amine moiety, a phenolic hydroxyl moiety, a phosphate moiety, and a carboxyl moiety.

8. The implantable bioprosthesis of claim 2, wherein the implantable bioprosthesis is treated with a second stabilization reagent.

9. The implantable bioprosthesis of claim 8, wherein the second stabilization reagent is a cross-linking reagent.

10. The implantable bioprosthesis of claim 8, wherein the second stabilization reagent is a calcification inhibitor.

11. The implantable bioprosthesis of claim 10, wherein the calcification inhibitor is aluminum chloride.

12. The implantable bioprosthesis of claim 8, wherein the second stabilization reagent is a glycosaminoglycan-stabilizing reagent.

13. The implantable bioprosthesis of claim 12, wherein the glycosaminoglycan-stabilizing reagent is a carbodiimide.