Inhibition of in vitro calcium phosphate precipitation in presence of polyurethane via surface modification and drug delivery.

Abstract

Biomaterial associated calcification is the principal cause of the clinical failure of bioprosthetic implants. The present investigation describes the mineralization of polymeric substrate in an extracirculatory environment and the possible methods of prevention. Calcification was examined on various polyurethane films (and bioprosthetic tissue) incubated in metastable solutions of calcium phosphate and the role of polymer casting and precipitation was evaluated. The formulation and the in vitro efficacy of prolonged controlled-release chitosan matrices, containing the novel anticalcification agents, such as Fe +++ or protamine 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 spectrophotometrically. The amount and percentage of drug release were much higher initially, which was controlled with the incorporation of egg phosphatidyl choline (EPC). The PS loaded chitosan beads (coincubated in calcium phosphate solution with the calcifiable polyurethane films) significantly inhibited biomaterial calcification (about 40-50% inhibition). Surface modification of polyurethanes with Fe +++ or PS also inhibited the calcification profile of the material. These findings suggest the possibility of a combination therapy for prevention of biomaterial associated calcification via surface modifications in conjunction with long-term controlled release of the anticalcifying drugs.