title: Polymer-free immobilization of a cyclic RGD peptide on a nitinol stent promotes integrin-dependent endothelial coverage of strut surfaces.
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.
authors.affiliation: CVPath Institute, Gaithersburg, Maryland 20878, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Joner
authors.forename: Qi
authors.initials: Q
authors.lastname: Cheng
authors.forename: Sabine
authors.initials: S
authors.lastname: Schönhofer-Merl
authors.forename: Monica
authors.initials: M
authors.lastname: Lopez
authors.forename: Stefanie
authors.initials: S
authors.lastname: Neubauer
authors.forename: Carlos
authors.initials: C
authors.lastname: Mas-Moruno
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Laufer
authors.forename: Frank D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
mesh_terms: D000497:Alloys / Q000737:chemistry*; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008422:Materials Testing; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011817:Rabbits; D015607:Stents; D013499:Surface Properties
chemical_list: D000497:Alloys; D020099:Coated Materials, Biocompatible; D009842:Oligopeptides; D010456:Peptides, Cyclic; C013616:nitinol; C047981:arginyl-glycyl-aspartic acid