Inhibition of calcification in vivo by acyl azide cross-linking of a collagen-glycosaminoglycan sponge.
A collagen-glycosaminoglycan sponge composed of collagen (80%), chondroitin-4-sulfate (13.3%) and heparan sulfate (6.6%) was cross-linked using the acyl azide method or glutaraldehyde (0.0075%). Under optimal conditions, the denaturation temperature (Td) was raised to 69 degrees C (+23 degrees C) for the sponge treated by the acyl azide method and to 68 degrees C (+22 degrees C) for that treated with glutaraldehyde. The biocompatibility of the treated and control sponges was studied up to 3 months after subcutaneous implantation in rats by analysing cellular responses and calcification by histological and ultrastructural methods. A control collagen-glycosaminoglycan sponge was rapidly invaded by mononuclear cells (8 days), with the formation of granulation tissue. Calcification was observed at the periphery of the implant after 8 days, and the implant was entirely calcified after 15 days; it was degraded progressively after 30 days. Acyl azide treatment increased the persistence of the sponge in vivo up to 90 days and inhibited its calcification. A glutaraldehyde-treated sponge was completely calcified after 15 days, and calcified nodules persisted after 90 days. Thus, acyl azide method efficiently cross-linked a collagen-glycosaminoglycan sponge and inhibited calcification after subcutaneous implantation in rats (at least up to 90 days after implantation).
Anselme
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Institut de Biologie et Chimie des Protéines, UPR CNRS 412, Université Claude Bernard, Villeurbanne, France.
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D000818:Animals; D001672:Biocompatible Materials; D002114:Calcinosis / Q000209:etiology / Q000517:prevention & control*; D003094:Collagen / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D005549:Foreign-Body Reaction / Q000473:pathology*; D005976:Glutaral / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000737:chemistry*; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism; D015503:Surgical Sponges
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D006025:Glycosaminoglycans; D006834:Hydrazines; C077715:glycagen; C029424:hydrazine; D003094:Collagen; D005976:Glutaral