Inhibition of calcification of bioprosthetic heart valves by local controlled-release diphosphonate

Bioprostheses fabricated from porcine aortic valves are widely used to replace diseased heart valves. Calcification is the principal cause of the clinical failure of these devices. In the present study, inhibition of the calcification of bioprosthetic heart valve cusps implanted subcutaneously in rats was achieved through the adjacent implantation of controlled-release matrices containing the anticalcification agent ethanehydroxydiphosphonate dispersed in a copolymer of ethylene-vinyl acetate. Prevention of calcification was virtually complete, without the adverse effects of retarded bone and somatic growth that accompany systemic administration of ethanehydroxydiphosphonate.