Bioprosthetic tissue with reduced calcification

• US 10,188,511 B2
• Filed: 04/25/2016
• Issued: 01/29/2019
• Est. Priority Date: 12/21/2007
• Status: Active Grant

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Edwards Lifesciences Corporation
• Inventors: Dove, Jeffrey S., Dobler, Darin P., Davidson, James A., Wright, Gregory A.
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Mercier, Melissa S
• Application Number:
  US15/138,123
• Publication Number:
  US 20160235528A1
• Time in Patent Office: 1,009 Days
• Field of Search: None
• CPC Class Codes: A61F 2/0095 Packages or dispensers for prostheses or other implants for intraocular lenses A61F2/1691; for dental surgery A61C19/02
• CPC Class Codes: A61F 2/2412 with soft flexible valve members, e.g. tissue valves shaped like natural valves check valves with flexible valve members in general F16K15/14
• CPC Class Codes: A61F 2/2415 Manufacturing methods
• CPC Class Codes: A61F 2/2418 Scaffolds therefor, e.g. support stents
• CPC Class Codes: A61L 2400/02 Treatment of implants to prevent calcification or mineralisation in vivo
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• 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 27/3629 Intestinal tissue, e.g. small intestinal submucosa
• 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
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062

Abstract

A treatment for bioprosthetic tissue used in implants or for assembled bioprosthetic heart valves to reduce in vivo calcification. The method includes applying a calcification mitigant such as a capping agent or an antioxidant to the tissue to specifically inhibit oxidation in tissue. Also, the method can be used to inhibit oxidation in dehydrated tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the oxidation and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. In one method, tissue leaflets in assembled bioprosthetic heart valves are pretreated with an aldehyde capping agent prior to dehydration and sterilization.

Claims

1. A packaged bioprosthetic device comprising:

an at least partially cross-linked pericardial tissue comprising functional groups that have been blocked, removed or altered by reacting the functional groups with capping agents, wherein the functional groups are one or both of aldehyde groups and carboxylic acid groups; and

a packaging storing the at least partially cross-linked biological tissue without a liquid preservative solution.

2. The packaged bioprosthetic device of claim 1, wherein the bioprosthetic device is a bioprosthetic heart valve comprising a stent coupled to leaflets made from the at least partially cross-linked biological tissue.

3. The packaged bioprosthetic device of claim 1, wherein the biological tissue is at least partially cross-linked with glutaraldehyde or other aldehyde-containing agents.

4. The packaged bioprosthetic device of claim 1, wherein the at least a portion of the functional groups are blocked, removed or altered by exposing the at least partially cross-linked biological tissue to a reducing agent.

5. The packaged bioprosthetic device of claim 1, wherein the at least partially cross-linked biological tissue comprises glycerol.

6. The packaged bioprosthetic device of claim 5, wherein the at least partially cross-linked biological tissue and the packaging is sterilized by ethylene oxide, gamma irradiation or electron beam irradiation.

7. The packaged bioprosthetic device of claim 1, wherein the at least partially cross-linked biological tissue is at least partially dehydrated.

8. The packaged bioprosthetic device of claim 7, wherein the at least partially cross-linked biological tissue and the packaging is sterilized by ethylene oxide, gamma irradiation or electron beam irradiation.

9. The packaged bioprosthetic device of claim 1, wherein the capping agent is one or more selected from the group consisting of:

an amine, an alkyl amine, an amino alcohol, an ethanolamine, an amino acid, a lysine, a hydroxylysine, an amino sulfonate, a taurine, an amino sulfate, a dextran sulfate, a chondroitin sulfate, a hydrophilic multifunctional polymer, a polyvinyl alcohol, a polyethyleneimine, a hydrophobic multifunctional polymer, an α

-dicarbonyl, a methylglyoxal, a 3-deoxyglucose, a glyoxal, a hydrazide, an adipic hydrazide, a heparin, a mono-epoxy alkane, a di-epoxy alkane, and a polyepoxyalkane.

10. The packaged bioprosthetic device of claim 9, wherein the functional groups have been reacted with a reducing agent.

11. The packaged bioprosthetic device of claim 10, wherein the reducing agent is selected from the group consisting of:

a sodium borohydride and a sodium cyanoborohydride.

12. The packaged bioprosthetic device of claim 11, wherein the bioprosthetic tissue comprises glycerol.

13. The packaged bioprosthetic device of claim 1, wherein the biological tissue is at least partially cross-linked with glutaraldehyde or an aldehyde-containing agent.

14. The packaged bioprosthetic device of claim 1, wherein the capping agent is one or more selected from the group consisting of:

an amine, an alkyl amine, an amino alcohol, an ethanolamine, an amino acid, a lysine, a hydroxylysine, an amino sulfonate, a taurine, an amino sulfate, a dextran sulfate, a chondroitin sulfate, a hydrophilic multifunctional polymer, a polyvinyl alcohol, a polyethyleneimine, a hydrophobic multifunctional polymer, an α

-dicarbonyl, a methylglyoxal, a 3-deoxyglucose, a glyoxal, a hydrazide, an adipic hydrazide, a heparin, a mono-epoxy alkane, a di-epoxy alkane, and a polyepoxyalkane.

15. The packaged bioprosthetic device of claim 1, wherein the functional groups have been reacted with a reducing agent.

16. The packaged bioprosthetic device of claim 15, wherein the reducing agent is selected from the group consisting of:

a sodium borohydride and a sodium cyanoborohydride.

17. The packaged bioprosthetic device of claim 16, wherein the bioprosthetic tissue comprises glycerol.