Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice

Sakine Simsekyilmaz, Elisa A. Liehn, Stefan Weinandy, Fabian Schreiber, Remco T. A. Megens, Wendy Theelen, Ralf Smeets, Stefan Jockenhoevel, Thomas Gries, Martin Moeller, Doris Klee, Christian Weber, Alma Zernecke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

Abstract

Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE-/- carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.
Original languageEnglish
Article numbere0155829
JournalPLOS ONE
Volume11
Issue number5
DOIs
Publication statusPublished - 18 May 2016

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