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bioRxiv · 10.1101/2022.05.25.493423

Intraprocedural endothelial cell seeding of arterial stents via biotin/avidin targeting mitigates in-stent restenosis

Alferiev, I. S.·Hooshdaran, B.·Pressly, B. B.·Stachelek, S. J.·Zoltick, P. W.·Chorny, M.·Levy, R. J.·Fishbein, I.
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Abstract

Impaired endothelialization of endovascular stents has been established as a major cause of in-stent restenosis and late stent thrombosis[1]. Attempts to enhance endothelialization of inner stent surfaces by pre-seeding the stents with endothelial cells in vitro prior to implantation are compromised by cell destruction during high-pressure stent deployment. Herein, we report on the novel stent endothelialization strategy of post-deployment seeding of biotin-modified endothelial cells to avidin-functionalized stents. Acquisition of an avidin monolayer on the stent surface was achieved by consecutive treatments of bare metal stents (BMS) with polyallylamine bisphosphonate, an amine-reactive biotinylation reagent and avidin. Biotin-modified endothelial cells retain growth characteristics of normal endothelium and can express reporter transgenes. Under physiological shear conditions, a 50-fold higher number of recirculating biotinylated cells attached to the avidin-modified metal surfaces compared to bare metal counterparts. Delivery of biotinylated endothelial cells to the carotid arterial segment proximal to the implanted avidin-modified stent in rats results in immediate cell binding to the stent struts and is associated with a 30% reduction of in-stent restenosis in comparison with BMS.

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Alferiev, I. S., Hooshdaran, B., Pressly, B. B., Stachelek, S. J., Zoltick, P. W., Chorny, M., Levy, R. J., Fishbein, I.. 2022-05-26. Intraprocedural endothelial cell seeding of arterial stents via biotin/avidin targeting mitigates in-stent restenosis. https://doi.org/10.1101/2022.05.25.493423

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