Prevention of polyurethane valve cusp calcification with covalently attached bisphosphonate diethylamino moieties

Ivan Alferiev, Stanley J. Stachelek, Zhibin Lu, Angela L. Fu, Tiffany L. Sellaro, Jeanne M. Connolly, Richard W. Bianco, Michael S. Sacks, Robert J. Levy

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Objective: Calcification of polyurethane prosthetic valve leaflets causes a major functional impairment. Previously we showed that polyurethane heart valves modified with covalently linked bisphosphonate groups were resistant to calcification in vivo. However, we also found that the highly polar anionic bisphosphonate groups on the polyurethane surface attracted sodium counter ion adsorption, and thereby increased the elastomer's water absorption to 20% of total weight. In this study we address the increased water absorption by investigating the hypothesis that covalently attaching cationic diethylamino groups to the bisphosphonate-modified polyurethane will reduce water absorption. Thus we evaluated the mechanical and in vivo anticalcification properties of heart-valve leaflets composed of this modified polymer. Methods: Diethylamino and bisphosphonate groups (DBP) were appended to the polyurethane Biospan's hard segment using previously published bromoalkylation methodology. Water absorption and biaxial mechanical and uniaxial failure testing were used to determine the mechanical properties of the DBP-modified polymer. Rat subdermal implants (60 days) and extended (150 days) single pulmonary leaflet replacements in juvenile sheep provided in vivo assessments of the bisphosphonate-modified polyurethane. Results: The water absorption properties of the DBP-modified polymers and unmodified polyurethanes were 1.86 and 2.3%, respectively. Biaxial mechanical tests showed the DBP-modified polymer was more compliant than the unmodified control material, but all polymeric material had similar uniaxial failure properties. In both rat subdermal and sheep circulatory implants, the DBP-modified polyurethane resisted calcification, as assessed by scanning electron microscopy, with complete calcification inhibition in prosthetic sheep valve leaflet replacements. Conclusion: DBP polyurethane possesses physical (water absorption) and biomechanical properties comparable to unmodified polyurethane and can resist intrinsic heart-valve leaflet calcification in blood-stream implants.

Original languageEnglish (US)
Pages (from-to)385-395
Number of pages11
JournalJournal of Biomedical Materials Research - Part A
Volume66
Issue number2
DOIs
StatePublished - Aug 1 2003

Keywords

  • Biomechanics
  • Calcinosis
  • Heart-valve prostheses
  • Local delivery
  • Polymer

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