Sirolimus coating on heparinized stents prevents restenosis and thrombosis

J Biomater Appl. 2017 May;31(10):1337-1345. doi: 10.1177/0885328217706222. Epub 2017 Apr 24.

Abstract

The aim of this study was to evaluate the inhibitory effect of sirolimus coating on the occurrence of restenosis and thrombosis with heparinized stents. Heparin and dopamine were conjugated by chemical bonding and anchored on the stent surface by a mussel-inspired adhesion mechanism. Subsequently, sirolimus was coated with poly lactic-glycolic acid on the heparinized stent surface. The heparin was well attached to the surface, and the surface was smooth after sirolimus coating. The smoothness of the surface was maintained after expansion of the stent. The amount of sirolimus released from the stent was 67.3% ± 4.55% within 7 days, followed by continual release up to day 28. The proliferation of smooth muscle cells was successfully arrested (51.3% ± 2.25% at 7 days of culture) by sirolimus released from the stent. Platelet adhesion was clearly prevented in the heparin-coated group (78.0 ± 8.00/1.8 cm2) compared to that in the heparin noncoated group (5.0 ± 1.00/1.8 cm2). Animal studies showed that the heparin and sirolimus-coated stent group had no obvious inflammatory response and no change in the fibrin score compared to those in the other groups. However, restenosis clearly decreased in the heparin and sirolimus-coated group (12.3% ± 3.54%) compared to the bare-metal stent group (27.5% ± 8.52%) and the heparin-coated group (25.3% ± 11.79%). These results suggest that heparinized surface-based sirolimus coating may be a useful approach for the prevention of restenosis and stent thrombosis.

Keywords: Drug-eluting stent; animal study; anti-thrombosis; heparinized surface; in-stent restenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line
  • Cell Proliferation
  • Cell Survival
  • Coated Materials, Biocompatible
  • Coronary Restenosis / prevention & control*
  • Drug Delivery Systems
  • Drug Liberation
  • Drug-Eluting Stents*
  • Heparin / chemistry*
  • Humans
  • Iliac Artery / surgery
  • Kinetics
  • Platelet Adhesiveness
  • Rabbits
  • Rats
  • Sirolimus / chemistry*
  • Sirolimus / metabolism
  • Sirolimus / pharmacology
  • Surface Properties
  • Thrombosis / prevention & control*

Substances

  • Coated Materials, Biocompatible
  • Heparin
  • Sirolimus