Method of preparing calcification-resistant bioprosthetic tissue
Methods of preparing calcification-resistant bioprosthetic tissue include providing fresh biological tissue, cross-linking the tissue, treating the cross-linked tissue with an alcohol for a time sufficient to allow the alcohol to be diffused into the tissue, and treating the alcohol-treated fixed tissue with a polyol for a time sufficient to allow fluid in the tissue to be replaced by the polyol. The methods may include sterilizing the cross-linked tissue in a solution including propylene oxide or peracetic acid either before or after the alcohol treatment step; or drying the alcohol/polyol-treated, cross-linked tissue, sterilizing the dried tissue by exposure to ethylene oxide or peracetic acid, and storing the sterilized tissue in a dry, ambient environment. The treated tissue may be a tissue component for a bioprosthetic valve, a valve assembly for a bioprosthetic valve or a fully assembled bioprosthetic valve incorporating the tissue.
1. A method of preparing calcification-resistant tissue, comprising:
providing fresh biological tissue;
cross-linking the tissue to produce fixed tissue;
treating the fixed tissue with an alcohol for a time sufficient to allow the alcohol to be diffused into the tissue to produce alcohol-treated fixed tissue; and
treating the alcohol-treated fixed tissue with a polyol for a time sufficient to allow fluid in the tissue to be replaced by the polyol to produce alcohol/polyol-treated fixed tissue,
wherein the alcohol is at least one of a lower aliphatic (C 1 to C 8 ) alcohol, and the alcohol is in an aqueous solution comprising from about 85 v/v % to about 100 v/v % of the alcohol.
2. The method of claim 1 , further comprising sterilizing the fixed tissue in a solution comprising propylene oxide or peracetic acid prior to the step of treating the fixed tissue with the alcohol.
3. The method of claim 1 , further comprising sterilizing the alcohol/polyol-treated fixed tissue in a solution comprising propylene oxide or peracetic acid.
4. The method of claim 1 , further comprising:
drying the alcohol/polyol-treated fixed tissue to produce dried tissue; and
storing the dried tissue in a dry, ambient environment.
5. The method of claim 4 , further comprising placing the dried tissue in a package and sealing the package.
6. The method of claim 5 , further comprising sterilizing the package after the sealing step.
7. The method of claim 6 , wherein the sterilization step is performed by exposing the sealed package to ethylene oxide or peracetic acid.
8. The method of claim 1 , wherein the cross-linking step is performed by using a glutaraldehyde or formaldehyde aqueous solution.
9. The method of claim 1 , wherein the alcohol is ethanol.
10. The method of claim 1 , wherein the step of treating the fixed tissue with an alcohol is performed at a temperature between about 15° C. and about 30° C.
11. The method of claim 1 , wherein the polyol is at least one of a lower aliphatic diol or triol (C 1 to C 4 ).
12. The method of claim 1 , wherein the polyol is glycerol.
13. The method of claim 1 , wherein the polyol is in water or a 0.9 wt % aqueous saline solution comprising from about 20 v/v % to about 100 v/v % of polyol.
14. The method of claim 1 , wherein the step of treating the alcohol-treated fixed tissue with a polyol is performed at a temperature between about 15° C. and about 30° C.
15. The method of claim 1 , wherein the tissue is in the form of a tissue component, a valve assembly for a bioprosthetic valve or a fully assembled bioprosthetic valve incorporating the tissue.
16. Tissue prepared according to the method of claim 1 .
17. A method of preparing calcification-resistant tissue, comprising:
providing fresh biological tissue;
cross-linking the tissue to produce fixed tissue;
treating the fixed tissue with an alcohol for a time sufficient to allow the alcohol to be diffused into the tissue to produce alcohol-treated fixed tissue; and
treating the alcohol-treated fixed tissue with a polyol for a time sufficient to allow fluid in the tissue to be replaced by the polyol to produce alcohol/polyol-treated fixed tissue,
wherein the step of treating the fixed tissue with an alcohol is performed for about 12 hours to about 48 hours.
18. The method of claim 17 , wherein the alcohol is at least one of a lower aliphatic (C 1 to C 8 ) alcohol.
19. The method of claim 17 , wherein the alcohol is in an aqueous solution comprising from about 85 v/v % to about 100 v/v % of alcohol.
20. The method of claim 17 , wherein the polyol is at least one of a lower aliphatic diol or triol (C 1 to C 4 ).
21. A method of preparing calcification-resistant tissue, comprising:
providing fresh biological tissue;
cross-linking the tissue to produce fixed tissue;
treating the fixed tissue with an alcohol for a time sufficient to allow the alcohol to be diffused into the tissue to produce alcohol-treated fixed tissue; and
treating the alcohol-treated fixed tissue with a polyol for a time sufficient to allow fluid in the tissue to be replaced by the polyol to produce alcohol/polyol-treated fixed tissue,
wherein the step of treating the alcohol-treated fixed tissue with a polyol is performed for about 12 hours to about 48 hours.
22. The method of claim 21 , wherein the alcohol is at least one of a lower aliphatic (C 1 to C 8 ) alcohol.
23. The method of claim 21 , wherein the polyol is at least one of a lower aliphatic diol or triol (C 1 to C 4 ).