Bisphosphonate derivatized polyurethanes resist calcification

Calcification of polyurethane cardiovascular implants is an important disea se process that has the potential to compromise the long-term function of d evices such as polymer heart valves and ventricular assist systems In this study we report the successful formulation and characterization of bisphosp honate-derivatized polyurethanes, hypothesized to resist implant calcificat ion based on the pharmacologic activity of the immobilized bisphosphonate. Fully polymerized polyurethanes (a polyurea-polyurethane and a polycarbonat e polyurethane) were modified (post-polymerization) with bromoalkylation of the hard segments followed by attachment of a bisphosphonate group at the bromine site. These bisphosphonate-polyurethanes resisted calcification in rat 60 day subdermal implants compared to nonmodified control polyurethane implants, that calcify. Bisphosphonates-modified polyurethanes were also st udied in circulatory implants using a pulmonary valve cusp replacement mode l in sheep. Polyurethane cusps modified with bisphosphonate did not calcify in 90 day implants, compared to control polyurethane cusps implants, that demonstrated nodular surface oriented calcific deposits. It is concluded th at bisphosphonate modified polyurethanes resist calcification both in subde rmal implants and in the circulation. This novel biomaterial approach offer s great promise for long-term blood stream implantation with calcification resistance. (C) 2001 Elsevier Science Ltd. All rights reserved.