Polymer-free immobilization of a cyclic RGD peptide on a nitinol stent promotes integrin-dependent endothelial coverage of strut surfaces

J Biomed Mater Res B Appl Biomater. 2012 Apr;100(3):637-45. doi: 10.1002/jbm.b.31988. Epub 2012 Jan 25.

Abstract

This study examined the utility of a stabilized cyclic RGD peptide chemically modified to selectively bind to titanium-oxide for enhanced biocompatibility of self-expanding nitinol stents. Endothelial cells express integrin receptors that promote attachment to subendothelial matrix proteins. Integrin binding to arginine-glycine-aspartic acid (RGD) peptide derivatives mimic naturally occurring adherent interactions. Irreversible covalent surface coating of conventional nitinol stents with a cyclic RGD (cRGD) peptide highly specific for integrin alpha v beta 3 might foster endothelialization after stent implantation. A selective cRGD peptide was irreversibly immobilized onto titanium oxide-rich nitinol coupons or self-expanding stents. Functionality of the engrafted RGD peptide was demonstrated using in vitro endothelial bioassays. A subsequent 7-day in vivo endothelialization study was performed using cRGD-coated self-expanding nitinol stents in rabbits. cRGD peptide coating effectively promoted endothelial cell anchorage, migration, and proliferation confirmed by increased focal adhesions. Proof-of-concept studies of rabbit cRGD stent implants showed a significant increase in endothelial coverage above stent struts relative to stents coated with BSA (cRGD = 70.1 ± 21.9 vs. BSA = 49.9 ± 21.8%, p < 0.03). Immobilization of cRGD peptides on strut surfaces represents an innovative strategy to improve endothelialization, which may facilitate vascular healing after stent implantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloys / chemistry*
  • Animals
  • Cell Adhesion
  • Cells, Cultured
  • Coated Materials, Biocompatible*
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Humans
  • Male
  • Materials Testing*
  • Oligopeptides / chemistry*
  • Peptides, Cyclic / chemistry*
  • Rabbits
  • Stents*
  • Surface Properties

Substances

  • Alloys
  • Coated Materials, Biocompatible
  • Oligopeptides
  • Peptides, Cyclic
  • nitinol
  • arginyl-glycyl-aspartic acid