Tailoring of the dopamine coated surface with VEGF loaded heparin/poly-L-lysine particles for anticoagulation and accelerate in situ endothelialization

J Biomed Mater Res A. 2015 Jun;103(6):2024-34. doi: 10.1002/jbm.a.35339. Epub 2014 Oct 14.

Abstract

Coronary artery disease is a great threat to human health and is the leading killer worldwide. Percutaneous coronary intervention is the most effective therapy; however, thrombus, and restenosis caused by endothelium injury continue to be problematic after treatment. It is widely accepted that surface biofunctional modification to improve blood compatibility and accelerate endothelialization may be an effective approach to prevent the occurrence of adverse cardiac events. In this study, novel VEGF-loaded heparin/poly-L-lysine (Hep/PLL) particles were developed and immobilized on a dopamine coated titanium surface. The size, distribution, zeta potential, and morphology of the prepared particles were subsequently characterized. The influence of changes in the surface physicochemical properties after particle immobilization was assessed for blood compatibility and cytocompatibility. Surface-modified VEGF-loaded particles significantly inhibited platelet adhesion and activation and were effective in promoting the proliferation and survival of endothelial progenitor cells and endothelial cells. Moreover, Hep/PLL particles were also beneficial for controlling the long-term release of VEGF, which may facilitate endothelium regeneration. In conclusion, VEGF-loaded Hep/PLL particles were successfully immobilized on the Ti surface, and the biocompatibility was significantly improved. This study demonstrates a potential application for the multifunctional modification of stent surfaces for clinical use.

Keywords: VEGF; dopamine; endothelialization; heparin; titanium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Coagulation / drug effects*
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Coated Materials, Biocompatible / pharmacology*
  • Dopamine / pharmacology*
  • Heparin / pharmacology*
  • Human Umbilical Vein Endothelial Cells / cytology*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Kinetics
  • Materials Testing
  • Microscopy, Atomic Force
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Partial Thromboplastin Time
  • Particle Size
  • Photoelectron Spectroscopy
  • Platelet Adhesiveness / drug effects
  • Platelet Count
  • Polylysine / pharmacology*
  • Rats, Sprague-Dawley
  • Rhodamine 123 / metabolism
  • Spectroscopy, Fourier Transform Infrared
  • Static Electricity
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Vascular Endothelial Growth Factor A / pharmacology*
  • Water / chemistry

Substances

  • Coated Materials, Biocompatible
  • Vascular Endothelial Growth Factor A
  • Water
  • Rhodamine 123
  • Polylysine
  • Heparin
  • Dopamine