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 produce an acellular matrix vascular prosthesis (AMVP). Implanted as an allograft in a canine model, this AMVP shows excellent handling characteristics, low thromboreactivity, no evidence of aneurysm, and exceptional graft patency in the peripheral vasculature. As a first step in the development of xenograft AMVPs, we processed caprine carotid arteries to AMVP and implanted them 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 response to xenogenic AMVP, we implanted canine-derived AMVPs and fresh canine arteries for 4 weeks in a Lewis rat model. Extraction to AMVP markedly reduced the circulating antibody response to the xenogenic implants; however, histological analysis revealed that both xenograft arteries and AMVPs produced a marked immune response with penetration of mononuclear cells into the media and adventitia. To modify the immune response, we applied three crosslinking techniques to the canine AMVPs: glutaraldehyde, polyglycidyl ether, and carbodiimide. All crosslinkers significantly reduced degradation and cellular infiltration of the prostheses. However, crosslinking neither eliminated the chronic inflammatory response surrounding the implants nor reduced the humoral response to the xenogenic materials.
Courtman
D W
DW
Division of Cardiovascular Surgery and the Terrance Donnely Heart Centre, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B IW8, Canada. courtmand@aol.com
Errett
B F
BF
Wilson
G J
GJ
D000818:Animals; D001672:Biocompatible Materials; D001807:Blood Vessel Prosthesis; D003432:Cross-Linking Reagents; D004285:Dogs; D005109:Extracellular Matrix / Q000737:chemistry / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D014183:Transplantation, Heterologous
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents