INHIBITION OF IN-VITRO CALCIUM-PHOSPHATE PRECIPITATION IN PRESENCE OFPOLYURETHANE VIA SURFACE MODIFICATION AND DRUG-DELIVERY

Biomaterial associated calcification is the principal cause of the cli nical failure of bioprosthetic implants. The present investigation des cribes the mineralization of polymeric substrate in an extracirculator y environment and the possible methods of prevention. Calcification wa s examined on various polyurethane films (and bioprosthetic tissue) in cubated in metastable solutions of calcium phosphate and the role of p olymer casting and precipitation was evaluated. The formulation and th e in vitro efficacy of prolonged controlled-release chitosan matrices, containing the novel anticalcification agents, such as Fe+++ or prota mine sulfate (PS), were also attempted. The in vitro release profiles of PS from chitosan beads was performed in a rotating shaker (100 rpm) in 0.1 M phosphate buffer (pH 7.4) and was monitored spectrophotometr ically. The amount and percentage of drug release were much higher ini tially, which was controlled with the incorporation of egg phosphatidy l choline (EPC). The PS loaded chitosan beads (coincubated in calcium phosphate solution with the calcifiable polyurethane films) significan tly inhibited biomaterial calcification (about 40-50% inhibition). Sur face modification of polyurethanes with Fe+++ or PS also inhibited the calcification profile of the material. These findings suggest the pos sibility of a combination therapy for prevention of biomaterial associ ated calcification via surface modifications in conjunction with long- term controlled release of the anticalcifying drugs. (C) 1994 John Wil ey & Sons, Inc.