Method of treating a synthetic naturally occurring surface with a collagen laminate to support microvascular endothelial cell growth, and the surface itself

• US 5,131,907 A
• Filed: 03/06/1991
• Issued: 07/21/1992
• Est. Priority Date: 04/04/1986
• Status: Expired due to Term

• Current Assignee: Thomas Jefferson University (Main Line Health System)
• Original Assignee: Thomas Jefferson University (Main Line Health System)
• Inventors: Williams, Stuart K., Jarrell, Bruce E.
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): Low, Christopher S. F.
• Application Number:
  US07/666,475
• Time in Patent Office: 503 Days
• Field of Search: 435/240.241, 623/1, 424/93, 427/40, 427/41, 600/36
• US Class Current: 600/36
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: Y10S 623/921 Blood vessel

Abstract

A novel implantable prosthesis for implantation in human patients is disclosed which comprises a synthetic substrate and a Type IV/V collagen surface layer seeded with a confluent monolayer of autologous endothelial cells. In the preferred embodiment, a base layer of interstitial collagen is adhered to the substrate. The Type IV/V collagen surface layer is provided in a laminate comprising an intermediate layer of interstitial collagen which is covalently bound to the aforementioned base layer. A cross linking agent, such as glutaraldehyde, is utilized to covalently bind the interstitial collagen base layer to the substrate, and the collagen intermediate layer to the base layer. The cross linking agent is subsequently deactivated with a soluble peptide, such as lysine. Autologous endothelial cells, such as microvascular endothelial cells derived from adipose tissue, are then seeded at high densities on the pretreated graft material. Those cells adhere in suitable percentage within times compatible with most vascular surgical procedures, and, even more importantly, flatten on that surface to assume the appearance of a natural, cobblestone morphology. The subject surface is resistant to shear stress, and yields good results when tested as a vena cava implant in a dog.

Claims

1. A method for treating an intravascular implant prior to implantation in a human patient comprising the steps of:

(a) treating an implant comprising a synthetic substrate material by subjecting the implant to glow discharge etching for a period of time sufficient to improve the adherence of microvascular endothelial cells; and

(b) applying freshly isolated microvascular endothelial cells obtained from tissue having a high content of microvascular endothelial cells to provide about 50% or more confluence of said cells on the surface of said implant.

2. The method of claim 1 wherein said synthetic substrate is selected to a polyester material.

3. The method of claim 2 wherein said polyester material is a fibrous material.

4. The method of claim 3 wherein said polyester material is a woven material.

5. The method of claim 1 wherein said endothelial cells are isolated from fat tissue.

6. The method of claim 5 wherein said fat tissue is subcutaneous fat.

7. The method of claim 5 wherein said fat tissue is perinephric fat.

8. The method of claim 5 wherein said fat tissue is omentum.

9. The method of claim 5 wherein said fat tissue is intrathoracic fat.

10. The method of claim 5 wherein said fat tissue is intraperitoneal fat.