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The integrin ligand c(RGDf(NMe)Nal) reduces neointimal hyperplasia in a polymer-free drug-eluting stent system
Rechenmacher, Florian; Steigerwald, Kristin; Laufer, Burkhardt; Neubauer, Stefanie; Kapp, Tobias G.; Li, Liang; Mas Moruno, Carlos; Joner, Michael; Kessler, Horst
Universitat Politècnica de Catalunya. Departament de Ciència dels Materials i Enginyeria Metal·lúrgica; Universitat Politècnica de Catalunya. BIBITE - Biomaterials, Biomecànica i Enginyeria de Teixits
The use of highly active and selective integrin ligands in combination with stent implantation is emerging as a promising alternative to the release of classical immunosuppressive drugs by current drug-eluting stents (DES), which has been associated with delayed vascular healing and late stent thrombosis. Herein we present the development and biological evaluation of the integrin ligand c(RGDf(NMe)Nal) as a potent anti-proliferative molecule that targets coronary artery smooth muscle cells (CASMCs). This peptide showed an antagonistic activity for alpha v beta 3 and alpha v beta 5 in the low-nanomolar range, and selectivity against the platelet receptor alpha IIb beta 3. In vitro, it efficiently inhibited the proliferation of CASMCs, displaying higher potency than the anti-tumor drug candidate cilengitide. This peptide was then loaded into a polymer-free bare metal stent (BMS), and its release studied at different time points. Up to seven days of elution, the peptide-coated stents retained high antiproliferative activity toward CASMCs. Finally, the peptide was examined in vivo in a polymer-free DES system in a rabbit iliac artery model. After 28 days of implantation, histopathological analysis revealed that the peptide clearly decreased neointimal growth and improved vessel healing and re-endothelialization compared with the FDA-approved Cypher DES. Our study shows that this type of lipophilic integrin ligand, when eluted from a polymer-free stent system, has the potential to successfully decrease in-stent restenosis in the absence of delayed vascular healing.
Peer Reviewed
Àrees temàtiques de la UPC::Enginyeria dels materials
Tissue engineering
drug-eluting stents
integrin ligands
myocardial infarction
smooth muscle cells
Enginyeria de teixits
Attribution-NonCommercial-NoDerivs 3.0 Spain

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