Bisphosphonate derivatized polyurethanes resist calcification

Ivan Alferiev, Narendra Vyavahare, Cunxian Song, Jeanne Connolly, John Travis Hinson, Zhibin Lu, Sruthi Tallapragada, Richard Bianco, Robert Levy

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Calcification of polyurethane cardiovascular implants is an important disease process that has the potential to compromise the long-term function of devices such as polymer heart valves and ventricular assist systems. In this study we report the successful formulation and characterization of bisphosphonate-derivatized polyurethanes, hypothesized to resist implant calcification based on the pharmacologic activity of the immobilized bisphosphonate. Fully polymerized polyurethanes (a polyurea-polyurethane and a polycarbonate 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 studied in circulatory implants using a pulmonary valve cusp replacement model 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 that bisphosphonate modified polyurethanes resist calcification both in subdermal implants and in the circulation. This novel biomaterial approach offers great promise for long-term blood stream implantation with calcification resistance.

Original languageEnglish (US)
Pages (from-to)2683-2693
Number of pages11
JournalBiomaterials
Volume22
Issue number19
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
The authors thank Ms. Ginger Nicholson for her efforts in preparing the manuscript. This research was supported in part by the following grants: NIH-HL59730, The Mary W. Smith Trust, and The William J. Rashkind Endowment of The Children's Hospital of Philadelphia.

Keywords

  • Biomaterials
  • Heart valves
  • Mineralization
  • Prostheses

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