Treatment of bioprosthetic tissues to mitigate post implantation calcification
First Claim
1. A method for mitigating post-implantation calcification of a bioprosthetic material, said method comprising(a) adjusting the pH of a glutaraldehyde solution to a pH in the range of about 5.0 to 7.0;
- (b) contacting a quantity of biological tissue that contains connective tissue protein with the glutaraldehyde solution;
(c) heating the glutaraldehyde solution and the tissue to a temperature in the range of about 30 to 70°
C. for a period of time, thereby producing free amine groups on the tissue, wherein the tissue is(i) at least partially fixed prior to the performance of Step (c),(ii) fixed after the performance of Step (c), or(iii) fixed concurrently with the performance of Step (c),and wherein said tissue is fixed by immersing the tissue in a crosslinking solution comprising gluteraldehyde as a crosslinking agent; and
(d) contacting the fixed tissue with a solution containing a blocking reagent that blocks the free amine groups.
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Abstract
The present invention provides methods for treating tissue to inhibit post-implant calcification of a biological tissue. In one method of this invention, a tissue is immersed in or otherwise contacted with a pretreated glutaraldehyde solution, i.e., a heat-treated or pH-adjusted glutaraldehyde solution. The tissue may be partially fixed with glutaraldehyde prior to, after, or concurrently with the step of contacting the tissue with the pretreated gluteraldehyde. Contact with the pretreated gluteraldehyde produces free amine groups on the tissue, which are subsequently blocked by contacting the crosslinked tissue with a blocking agent. In another embodiment, a tissue is contacted with either a non-pretreated glutaraldehyde or a pH-adjusted glutaraldehyde solution for a period of time sufficient to crosslink the tissue. The crosslinked tissue is then treated with a reducing agent that reduces aldehyde and carboxylic acid groups on the fixed tissue.
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Citations
22 Claims
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1. A method for mitigating post-implantation calcification of a bioprosthetic material, said method comprising
(a) adjusting the pH of a glutaraldehyde solution to a pH in the range of about 5.0 to 7.0; -
(b) contacting a quantity of biological tissue that contains connective tissue protein with the glutaraldehyde solution; (c) heating the glutaraldehyde solution and the tissue to a temperature in the range of about 30 to 70°
C. for a period of time, thereby producing free amine groups on the tissue, wherein the tissue is(i) at least partially fixed prior to the performance of Step (c), (ii) fixed after the performance of Step (c), or (iii) fixed concurrently with the performance of Step (c), and wherein said tissue is fixed by immersing the tissue in a crosslinking solution comprising gluteraldehyde as a crosslinking agent; and (d) contacting the fixed tissue with a solution containing a blocking reagent that blocks the free amine groups. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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Specification