Calcification-resistant bioprosthetic tissue and methods of making same
AssigneeThe Board of Regents of the University of Michigan
InventorsRobert J. Levy, Eyal Lerner
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Abstract
Naturally-derived bioprosthetic materials are treated with epoxide crosslinking agents. In some embodiments, the tissue is crosslinked with low molecular weight epoxides in aqueous solutions at high pH levels. In other embodiments, the tissue is crosslinked at physiologic pH levels with epoxide crosslinking agents catalyzed with tertiary or quaternary amines, such as Tris or imidazole. In an advantageous embodiment, bioprosthetic tissue is crosslinked and derivatized with an anticalcification agent, such as a polyphosphonate anticalcification agent, using a polyphosphonate:polyepoxide monoadduct.
Claims8
A method of cross-linking bioprosthetic tissue comprising the steps of:
- (a) adding a polyphosphonate anticalcification agent to an excess of a polyepoxide to form a solution of polyphosphonate:polyepoxide monoadduct and excess polyepoxide;
- (b) diluting said solution with water;
- and
- (c) subjecting bioprosthetic tissue to the diluted solution for a time sufficient to crosslink the bioprosthetic tissue with the excess polyepoxide and to derivatize irreversibly the bioprosthetic tissue with the monoadduct.
The method of claim 7 wherein the diluted solution is buffered with a catalytic amine to a physiologic pH in the range of 7.0 to 8.0.
Dependencies are inferred from the claim text.