MODIFICATION OF NATIVE COLLAGEN REDUCES ANTIGENICITY BUT PRESERVES CELL COMPATIBILITY

Porcine intestinal collagen (ICL), derived from processed smalt intest ine, is used as a part of a remodelable bilaminate biosynthetic vascul ar prosthesis. The process for the production of ICL involves mechanic al cleaning of non-crosslinked porcine intestine (NC-ICL), disinfectio n with peracetic acid (PA-ICL), and crosslinking with 1-ethyl-3-(3-dim ethylaminopropyl) carbodiimide hydrochloride (PA/EDC-ICL). Two model s ystems were investigated to evaluate the effect of these agents on the humoral response to NC-ICL. First, the antibody titers of rabbits imm unized with NC-ICL, PA-ICL, and PA/EDC-ICL were determined, and second , the humoral response of canines receiving collagenous vascular impla nts was examined. Collagenous and noncollagenous fractions were extrac ted from NC-ICL, PA-ICL, and PA/EDC-ICL and separated by SDS-PAGE. PA and EDC treatment decreased the number of extractable proteins as comp ared to NC-ICL. Immunoblot techniques demonstrated anti-NC-ICL antibod ies recognized mutliple immunoreactive proteins in NC-ICL, but not in PA-ICL or PA/EDC-ICL; and rabbits immunized with NC-ICL produced highe r antibody titers to ICL proteins than rabbits immunized with either P A-ICL or PA/EDC-ICL. It was, therefore, apparent that NC-ICL was more antigenic than either PA-ICL or PA/EDC-ICL. The humoral Immune respons e of canines to PA/EDC-ICL fabricated vascular grafts was determined. At 4 weeks, 8 weeks, and 12 weeks postimplant, serum antibodies to ICL proteins or type I collagen could not be detected. These data demonst rate a reduced humoral immune response to PA/EDC-ICL. (C) 1996 John Wi ley & Sons, Inc.