Enhancement of xenogeneic tissue

• US 4,798,611 A
• Filed: 10/14/1986
• Issued: 01/17/1989
• Est. Priority Date: 10/14/1986
• Status: Expired due to Term

• Current Assignee: HJL LLC
• Original Assignee: Hancock Jaffe Laboratories, Inc.
• Inventors: Freeman, Donald C. Jr.
• Primary Examiner(s): Apley, Richard J.
• Assistant Examiner(s): PREBILIC, PAUL B
• Application Number:
  US06/918,280
• Time in Patent Office: 826 Days
• Field of Search: 8/94.11, 8/94.1, 8/94.19 R, 8/94.20, 128/1 R, 128/DIG. 8, 623/1, 623/2, 623/11, 623/13, 623/66
• US Class Current: 600/36
• CPC Class Codes: A61L 2/0035 Gamma radiation
• 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: Y10S 128/08 Collagen

Abstract

Xenogeneic tissue implants prepared by precrosslinking proteins in xenogeneic tissue using, for example, glutaraldehyde, and thereafter irradiating the crosslinked tissue with high energy radiation, e.g. gamma radiation, to sterilize, reduce the immunogenicity and improve the compliance and physical properties of the tissue are disclosed.

Claims

1. The method of preparing a xenogeneic tissue from animal tissue structures such as tendons, ligaments, pericardial membrane, skin, umbilical cord, and the like, without disintegration or comminution and reconstitution, for implantation comprising the steps of:

(a) removing excess tissue and fat from a tissue structure of an animal;

(b) cutting the tissue structure to a desired size and configuration;

(c) treating the tissue structure resulting from the preceding steps (a) and (b) with a chemical cross-linking reagent to effect cross-linking of the tissue constituents; and

, thereafter

(d) irradiating the tissue structure resulting from step (c) with high energy X-radiation or gamma radiation with from about two times to about five times the amount of such radiation as is necessary to sterilize said tissue structure, said amount of radiation being sufficient to sterilize the tissue structure but less than the amount of radiation which significantly (i) reduces shrink temperature T_s, (ii) increases the extractability of degradation products, and (iii) decreases the tensile strength of the tissue structure, and which renders the tissue structure more flexible and compliant, and less antigenic than the unirradiated tissue structure.

2. The method of claim 1 wherein the tissue is irradiated with from about two to about eight megarads of gamma radiation.

3. The process of claim 1 wherein the chemical crosslinking reagent is glutaraldehyde.

4. The method of claim 3 wherein the tissue is irradiated with from about two to about eight megarads of gamma radiation.

5. A xenogeneic graft tissue prepared from animal tissue structures such as tendons, ligaments, pericardial membrane, skin, umbilical cord, and the like, comprising the steps of:

(a) removing excess tissue and fat from a tissue structure of an animal and cutting the tissue to a desired size and configuration, all without disintegrating or comminuting the tissue;

(b) treating the tissue from step (a) with a chemical crosslinking reagent to effect cross-linking of the tissue constituents, and

(c) treating the tissue structure from step (b) with high energy X-radiation or gamma radiation with from about two times to about five times the amount of such radiation as is necessary to sterilize said tissue structure, said amount of radiation being sufficient to sterilize the tissue structure but less than the amount of radiation which significantly (i) reduces shrink temperature T_s, (ii) increases the extractability of degradation products, and (iii) decreases the tensile strength of the tissue structure, and which renders the tissue structure more flexible and compliant, and less antigenic than the unirradiated tissue structure.

6. The tissue of claim 5 wherein the irradiation is with from about two to about eight megarads of gamma radiation.

7. The tissue of claim 6 wherein the cross-linking is carried out with glutaraldehyde.

8. The tissue of claim 5 wherein the cross-linking is carried out with glutaraldehyde.