Non-calcific biomaterial by glutaraldehyde followed by oxidative fixation

• US 6,093,530 A
• Filed: 02/06/1998
• Issued: 07/25/2000
• Est. Priority Date: 02/06/1998
• Status: Expired due to Term

• Current Assignee: Corcym SRL (LivaNova Plc)
• Original Assignee: Sulzer Carbomedics Inc. (Zimmer Biomet Holdings, Inc.)
• Inventors: Moore, Mark A., Phillips, Richard E., McIlroy, Brian K.
• Primary Examiner(s): SAUCIER, SANDRA E
• Application Number:
  US09/019,749
• Time in Patent Office: 900 Days
• Field of Search: 435/1.1, 424/423, 623/2
• US Class Current: 435/1.1
• CPC Class Codes: A61L 2400/02 Treatment of implants to prevent calcification or mineralisation in vivo
• 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 27/3641 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 27/3691 characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation

Abstract

This invention relates to tanning biomaterial to obtain calcification resistant biomaterial with good mechanical properties for bioprosthetic applications. The biomaterial of the invention is obtained by tanning tissue by any method except by oxidation, and then at a later time tanning the tissue by any of the oxidative fixation methods. The process was shown to provide beneficial results with the most frequently used fixation process, which involves fixating tissue with glutaraldehyde. Tissue fixated with glutaraldehyde and then by oxidative fixation has a lower calcification potential than does glutaraldehyde-only tanned tissue and has mechanical properties more similar to glutaraldehyde tanned tissue than to oxidative stabilized tissue. In particular, a process is described where tissue is fixed with glutaraldehyde followed by photoxidation.

Claims

1. The process of producing calcification retardant biomaterial suitable for use in a bioprosthesis, said biomaterial comprising a biological tissue, said process comprising:

(1) fixating biomaterial by a glutaraldehyde fixation process; and

(2) subsequently fixating the biomaterial by an oxidative process which comprises a photooxidation process.

2. The process of claim 1 wherein the fixation process comprises exposing the biomaterial to glutaraldehyde in buffered saline solution.

3. The process of claim 1 wherein the fixation process comprises exposing the biomaterial to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 10 to 100°

C., followed by exposing the biomaterial to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 15°

to 30°

C., followed by exposing the biomaterial to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 30°

to 44°

C.

4. The process of claim 1 wherein the fixation process comprises exposing the biomaterial to glutaraldehyde in buffered saline solution, and then at a later time the photooxidation process comprises exposing the biomaterial to a solution containing a photosensitive dye, and then exposing the biomaterial in the solution to light in quantities sufficient to cause crosslinking of the tissue.

5. The process of claim 1 wherein the fixation process comprises exposing the biomaterial to glutaraldehyde in buffered saline solution, and the photooxidation process comprises exposing the biomaterial to a solution comprising dissolved oxygen and one or more of a compound selected from methylene blue, methylene green, rose bengal, riboflavin, proflavin, fluorescein, rosin, and pyridoxal-5-phosphate, and then exposing the biomaterial in the solution to light in quantities sufficient to cause crosslinking of the biomaterial.

6. The process of claim 1 wherein the fixation process comprises exposing the biomaterial to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 1°

to 10°

C., followed by exposing the biomaterial to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 15°

to 30°

C., followed by exposing the biomaterial to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 30°

to 44°

C., and the photooxidation process comprises exposing the biomaterial to a solution comprising dissolved oxygen and one or more of a compound selected from methylene blue, methylene green, rose bengal, riboflavin, proflavin, fluorescein, rosin, and pyridoxal-5-phosphate, and then exposing the tissue in the solution to light in quantities sufficient to cause crosslinking of the tissue.

7. The process of claim 1 wherein the fixation process comprises exposing the biomaterial to glutaraldehyde in buffered saline solution, and the photooxidation process comprises exposing the biomaterial to a solution comprising dissolved oxygen and riboflavin, and then exposing the biomaterial in the solution to light in quantities sufficient to cause crosslinking of the biomaterial.

8. The process of claim 1 wherein the fixation process comprises exposing the biomaterial to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 1°

to 10°

C., followed by exposing the tissue to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 15°

to 30°

C., followed by exposing the biomaterial to glutaraldehyde in phosphate buffered saline solution for about 12 to 36 hours at a temperature from about 30°

to 44°

C., and the photooxidation process comprises exposing the biomaterial to a solution comprising dissolved oxygen and riboflavin, and then exposing the biomaterial in the solution to light in quantities sufficient to cause crosslinking of the tissue.

9. The process of claim 1, wherein said calcification retardant biomaterial is stable following implantation in a host.

10. The process of claim 1, wherein said biological tissue is a heart tissue.