Polymer-free immobilization of a cyclic RGD peptide on a nitinol stent promotes integrin-dependent endothelial coverage of strut surfaces†
Sabine Schönhofer-Merl
Department of Cardiology, Deutsches Herzzentrum and Institute for Advanced Study, Munich, Germany
Search for more papers by this authorMonica Lopez
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorStefanie Neubauer
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorCarlos Mas-Moruno
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorBurkhardt Laufer
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorCorresponding Author
Frank D. Kolodgie
CVPath Institute, Gaithersburg, Maryland 20878
CVPath Institute, Gaithersburg, Maryland 20878Search for more papers by this authorHorst Kessler
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorSabine Schönhofer-Merl
Department of Cardiology, Deutsches Herzzentrum and Institute for Advanced Study, Munich, Germany
Search for more papers by this authorMonica Lopez
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorStefanie Neubauer
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorCarlos Mas-Moruno
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorBurkhardt Laufer
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorCorresponding Author
Frank D. Kolodgie
CVPath Institute, Gaithersburg, Maryland 20878
CVPath Institute, Gaithersburg, Maryland 20878Search for more papers by this authorHorst Kessler
Department Chemie, Center of Integrated Protein Science, Technische Universität München, Garching, Germany
Search for more papers by this authorHow to cite this article: Joner M, Cheng Q, Schönhofer-Merl S, Lopez M, Neubauer S, Mas-Moruno C, Laufer B, Kolodgie FD, Kessler H, Virmani R. 2012. Polymer-free immobilization of a cyclic RGD peptide on a nitinol stent promotes integrin-dependent endothelial coverage of strut surfaces. J Biomed Mater Res Part B 2012:100B:637–645.
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. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Supporting Information
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