title: Chemically modified collagen: a natural biomaterial for tissue replacement.
abstract: Glutaraldehyde crosslinking 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 crosslinks. Tissues crosslinked with glutaraldehyde retain many of the viscoelastic properties of the native collagen fibrillar network which render them suitable for bioprostheses. Implants of collagenous materials crosslinked with glutaraldehyde are subject long-term to calcification, biodegradation, and low-grade immune reactions. We have attempted to overcome these problems by enhancing crosslinking through bridging of activated carboxyl groups with diamines and using glutaraldehyde to crosslink the epsilon-NH2 groups in collagen and the unreacted amines introduced by aliphatic diamines. This crosslinking reduces tissue degradation and nearly eliminates humoral antibody induction. Covalent binding of diphosphonates, specifically 3-amino-1-hydroxypropane-1, 1-diphosphonic acid (3-APD), and chondroitin sulfate to collagen or to the crosslink-enhanced collagen network reduces its potential for calcification. Platelet aggregation is also reduced by glutaraldehyde crosslinking and nearly eliminated by the covalent binding of chondroitin sulfate to collagen. The cytotoxicity of residual glutaraldehyde--leaching through the interstices of the collagen fibrils or the tissue matrix--and of reactive aldehydes associated with the bound polymeric glutaraldehyde can be minimized by neutralization and thorough rinsing after crosslinking and storage in a nontoxic bacteriostatic solution.
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials; D001705:Bioprosthesis; D002114:Calcinosis / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology; D005976:Glutaral / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006882:Hydroxyapatites / Q000378:metabolism; D003012:Microbial Collagenase / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011402:Pronase / Q000494:pharmacology; D011509:Proteoglycans / Q000494:pharmacology; D051381:Rats
chemical_list: D001672:Biocompatible Materials; D004164:Diphosphonates; D006882:Hydroxyapatites; D010710:Phosphates; D011509:Proteoglycans; D000244:Adenosine Diphosphate; D006493:Heparin; D002809:Chondroitin Sulfates; D003094:Collagen; D011402:Pronase; D003012:Microbial Collagenase; D002118:Calcium; D005976:Glutaral