Treated tissue for implantation and methods of preparation

• US 5,899,936 A
• Filed: 06/05/1995
• Issued: 05/04/1999
• Est. Priority Date: 03/14/1994
• Status: Expired due to Term

• Current Assignee: Cryolife Incorporated
• Original Assignee: Cryolife Incorporated
• Inventors: Goldstein, Steven
• Primary Examiner(s): Clarke, Robert A.
• Application Number:
  US08/463,171
• Time in Patent Office: 1,429 Days
• Field of Search: 623/2, 623/11, 435/240.1, 435/240.2, 435/325, 435/366, 435/371, 424/422, 424/423
• US Class Current: 128/898
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• 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 27/3625 Vascular tissue, e.g. heart valves
• 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 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• 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 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: Y10S 623/92 Method or apparatus for preparing or treating prosthetic
• CPC Class Codes: Y10S 623/921 Blood vessel

Abstract

This disclosure includes a method for generating a functional hybrid bioprosthesis. Tissue formed naturally of interstitial collagens is treated to kill native cells and remove potentially immunologically active soluble molecules. Then it may be treated sequentially with extracellular matrix adhesion factor, extracellular matrix glycosaminoglycan, and growth factor appropriate to the cell type required to function within the matrix, and incubating the transplant tissue matrix with cells that are either allogeneic or autologous for the recipient thereby imparting to the matrix the characteristics of the cell type and tissue selected. Tissues with a variety of functional bioactivities can thus be formed in vitro prior to graft transplantation or implantation which will exhibit reduced or no stimulation of an immunological response in the recipient.

Claims

1. A process for treating bodily tissue which has been harvested from a donor to improve its compatibility with the immune system of an implant recipient to which said tissue in untreated form is xenogeneic, comprising the steps of

treating said bodily tissue to form a decellularized tissue matrix;

applying to a decellularized tissue matrix an amount of one or more cellular adhesion factors effective to promote the subsequent adhesion of cultured cells within the tissue matrix, wherein the cellular adhesion factor comprises one or more extracellular proteins ordinarily associated with the tissue in a liquid vehicle;

and then repopulating the tissue matrix with cells which are autologous or allogeneic to said recipient to provide a substantially non-immunogenic and biomechanically acceptable implant or graft which is vitalized by the cellular repopulation and is otherwise histologically and biochemically similar to the untreated tissue.

2. The process of claim 1 wherein the tissue treated is connective tissue, heart tissue or collagenous or vascular tissue.

3. The process of claim 2 wherein the adhesion factors include a glycoprotein and a glycosaminoglycan.

4. The process of claim 3 wherein the tissue matrix is repopulated with fibroblast cells immunologically compatible with the implant recipient.

5. The process of claim 4 wherein the fibroblast cells are modified genetically by techniques of stable transfection with exogenous genetic material.

6. The process of claim 4 wherein the fibroblast cells are of human origin and are modified to be substantially non-immunogenic upon implantation.

7. The process of claim 4 wherein the fibroblast cells are of human origin and are modified by genetic manipulation to express specific proteins.

8. The process of claim 4 wherein the adhesion factor is comprised of fibronectin and a glycosaminoglycan selected from the group consisting of dermatin, dermatin sulfate, chondroitin, chondroitin sulfate, heparin sulfate and heparin.

9. The process of claim 8 wherein the tissue is porcine heart valve tissue, and wherein the cellular repopulation step is conducted by incubating the tissue matrix in a nutrient environment and in the presence of fibroblast cells and an effective amount of fibroblast growth factor.