Growth factors-loaded stents modified with hyaluronic acid and heparin for induction of rapid and tight re-endothelialization

Colloids Surf B Biointerfaces. 2016 May 1:141:602-610. doi: 10.1016/j.colsurfb.2016.01.028. Epub 2016 Jan 21.

Abstract

Rapid re-endothelialization of damaged vessel lining efficiently prevents restenosis and thrombosis and restores original vascular functions. In this study, we designed a novel metallic stent with a heparin-modified surface and used different methods, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and divinyl sulfone (DVS), to load growth factors. First we loaded heparin into a dopamine-conjugated hyaluronic acid (HA) coating to serve as a growth factor reservoir. In a second step, we took advantage of the heparin-binding domain of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) to gain advanced re-endothelialization capabilities. We demonstrated that DVS technique offered higher amount of growth factor loading. In vitro assessment also showed better capillary-like structure formation and localized gap junctions when DVS coating was employed. This study suggested that growth factor loaded stent modified by HA and heparin provided the advantage to rapid and tight restoration of endothelium.

Keywords: Dopamine; Growth factor; Heparin; Hyaluronic acid; Re-endothelialization; Stent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Drug Liberation
  • Drug-Eluting Stents*
  • Ethyldimethylaminopropyl Carbodiimide / chemistry
  • Heparin / chemistry*
  • Hepatocyte Growth Factor / chemistry
  • Hepatocyte Growth Factor / pharmacokinetics
  • Hepatocyte Growth Factor / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Hyaluronic Acid / chemistry*
  • Magnetic Resonance Spectroscopy
  • Microscopy, Electron, Scanning
  • Microscopy, Fluorescence
  • Spectroscopy, Fourier Transform Infrared / methods
  • Sulfones / chemistry
  • Surface Properties
  • Vascular Endothelial Growth Factor A / chemistry
  • Vascular Endothelial Growth Factor A / pharmacokinetics
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Sulfones
  • Vascular Endothelial Growth Factor A
  • divinyl sulfone
  • Hepatocyte Growth Factor
  • Hyaluronic Acid
  • Heparin
  • Ethyldimethylaminopropyl Carbodiimide