Heparin/poly-l-lysine nanoplatform with growth factor delivery for surface modification of cardiovascular stents: The influence of vascular endothelial growth factor loading

J Biomed Mater Res A. 2020 Jun;108(6):1295-1304. doi: 10.1002/jbm.a.36902. Epub 2020 Feb 27.

Abstract

The rapid re-endothelialization of the vascular stent surface is desirable for preventing thrombosis or reducing restenosis. Many biological factors that promote the biological behavior of endothelial cells have been used for the surface modification of stents. Vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, induces strong vascular growth. In this study, we investigated different VEGF concentrations (50 to 500 ng/ml) to determine the optimum concentration for biocompatibility. First, VEGF-loaded heparin/poly-l-lysine (Hep-PLL) nanoparticles were created by electrostatic interactions. Then, the VEGF-loaded nanoparticles were immobilized on dopamine-coated 316 L stainless steel (SS) surfaces. The physical and chemical properties of the modified surface were characterized and the biocompatibility was evaluated in vitro. The results indicated that the VEGF-loaded nanoparticles were immobilized successfully on the 316LSS surface, as evidenced by the results of Alcian Blue staining and water contact angle (WCA) measurements. The low platelet adhesion and activation indicated that the modified surfaces had good blood compatibility. The modified surfaces showed a good inhibitory effect on smooth muscle cells, indicating that they inhibited tissue hyperplasia. In addition, the modified surfaces significantly promoted endothelial cell adhesion, proliferation, migration, and biological activity, especially VEGF concentration was 350 ng/ml (NPV350). The optical VEGF concentration of the surface modified Hep-PLL nanoparticles was 350 ng/ml. The proposed method shows promise for potential applications for cardiovascular devices.

Keywords: VEGF; anti-adhesion; endothelial cells; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / chemistry*
  • Anticoagulants / pharmacology
  • Blood Platelets / drug effects
  • Cell Line
  • Coated Materials, Biocompatible / chemistry*
  • Coated Materials, Biocompatible / pharmacology
  • Drug-Eluting Stents*
  • Heparin / chemistry*
  • Heparin / pharmacology
  • Humans
  • Materials Testing
  • Nanoparticles / chemistry
  • Platelet Adhesiveness / drug effects
  • Polylysine / chemistry*
  • Polylysine / pharmacology
  • Stainless Steel / chemistry
  • Surface Properties
  • Vascular Endothelial Growth Factor A / administration & dosage*
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Anticoagulants
  • Coated Materials, Biocompatible
  • Vascular Endothelial Growth Factor A
  • Stainless Steel
  • Polylysine
  • Heparin