Thromboresistant and endothelialization effects of dopamine-mediated heparin coating on a stent material surface

J Mater Sci Mater Med. 2012 May;23(5):1259-69. doi: 10.1007/s10856-012-4587-5. Epub 2012 Mar 3.

Abstract

Heparinization of surfaces has proven a successful strategy to prevent thrombus formation. Inspired by the composition of adhesive proteins in mussels, the authors used dopamine to immobilize heparin on a stent surface. This study aimed to assess the thromboresistant and endothelialization effects of dopamine-mediated heparin (HPM) coating on a stent material surface. The HPM was synthesized by bonding dopamine and heparin chemically. Cobalt-chromium (Co-Cr) alloy disks were first placed in the HPM solution and applied to surface stability then underwent thromboresistant tests and human umbilical vein endothelial cells (HUVEC) cytotoxicity assays. The results showed not only thromboresistant activity and a stable state of heparin on the surfaces after investigation with toluidine blue and thrombin activation assay but also proliferation of HUVEC in vitro. Studies on animals showed that the HPM-coated stent has no obvious inflammation response and increasing of restenosis rate compared to the bare metal stent (BMS) indicating good biocompatibility as well as safety in its in vivo application. Moreover, improving the endothelial cell (EC) proliferation resulted in a higher strut-covering rate (i.e., endothelialization) with shuttle-shaped EC in the HPM-coated stent group compared to that of the BMS group. These results suggest that this facile coating approach could significantly promote endothelialization and offer greater safety than the BMS for its much improved thromboresistant property. Moreover, it may offer a platform for conjugating secondary drugs such as anti-proliferative drugs.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dopamine / administration & dosage
  • Dopamine / chemistry
  • Dopamine / pharmacokinetics
  • Dopamine / pharmacology*
  • Drug-Eluting Stents*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / growth & development
  • Endothelium, Vascular / physiology
  • Heparin / administration & dosage
  • Heparin / pharmacokinetics
  • Heparin / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology
  • Rabbits
  • Thrombosis / prevention & control*

Substances

  • Heparin
  • Dopamine