The role of crosslinking in modification of the immune response elicited against xenogenic vascular acellular matrices

We have used detergent and enzymatic extraction of natural arteries to prod uce an acellular matrix vascular prosthesis (AMVP). Implanted as an allogra ft in a canine model, this AMVP shows excellent handling characteristics, l ow thromboreactivity, no evidence of aneurysm, and exceptional graft patenc y in the peripheral vasculature. As a first step in the development of xeno graft AMVPs, we processed caprine carotid arteries to AMVP and implanted th em as femoral interposition grafts in dogs. Explanted xenografts at 4 weeks showed multifocal mixed inflammatory infiltrates and focal destruction of the medial elastin in the inflammatory foci. To further study the immune re sponse to xenogenic AMVP, we implanted canine-derived AMVPs and fresh canin e arteries for 4 weeks in a Lewis rat model. Extraction to AMVP markedly re duced the circulating antibody response to the xenogenic implants; however, histological analysis revealed that both xenograft arteries and AMVPs prod uced a marked immune response with penetration of mononuclear cells into th e media and adventitia. To modify the immune response, we applied three cro sslinking techniques to the canine AMVPs: glutaraldehyde, polyglycidyl ethe r, and carbodiimide. All crosslinkers significantly reduced degradation and cellular infiltration of the prostheses. However, crosslinking neither eli minated the chronic inflammatory response surrounding the implants nor redu ced the humoral response to the xenogenic materials. (C) 2001 John Wiley & Sons, Inc. J Biomed Mater Res 55: 576-586, 2001.