The cross-linking and structure modification of the collagen matrix in the design of cardiovascular prosthesis.
Glutaraldehyde cross-linking of native or reconstituted collagen fibrils and tissues rich in collagen significantly reduces biodegradation. Other aldehydes are less efficient than glutaraldehyde in generating chemically, biologically, and thermally stable cross-links. Implants of collagenous materials cross-linked with glutaraldehyde are subject long-term to calcification, biodegradation, and low-grade immune reactions. We have attempted to overcome these problems by enhancing cross-linking through (a) bridging of activated carboxyl groups with diamines and (b) using glutaraldehyde to cross-link the epsilon-NH2 groups in collagen and the unreacted amines introduced by aliphatic dismines. This cross-linking reduces tissue degradation and nearly eliminates humoral antibody induction. Covalent binding of diphosphonates, specifically 3-amino-1-hydroxypopane-1, 1-diphosphonic acid (3-APD), and to a lesser extent chondroitin sulfate to collagen or to the cross-ling-enhanced collagen network reduces its potential for calcification. Platelet aggregation also is reduced by glutaraldehyde cross-linking and nearly eliminated by the covalent binding of chondroitin sulfate to collagen. The cytotoxicity of residual glutaraldehyde can be minimized by chemical neutralization and thorough rough rinsing.
Nimni
M E
ME
Department of Biochemistry, University of Southern California School of Medicine, Los Angeles.
D000244:Adenosine Diphosphate / Q000096:biosynthesis; D001705:Bioprosthesis / Q000592:standards*; D003094:Collagen / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D005976:Glutaral / Q000494:pharmacology*; D006350:Heart Valve Prosthesis / Q000009:adverse effects / Q000592:standards*; D006801:Humans; D008422:Materials Testing; D010974:Platelet Aggregation / Q000187:drug effects; D011402:Pronase / Q000494:pharmacology; D011474:Prosthesis Design
D000244:Adenosine Diphosphate; D003094:Collagen; D011402:Pronase; D005976:Glutaral