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    Spatiotemporal dual -delivery of therapeutic gas and growth factor for prevention of vascular stent thrombosis and restenosis

    Year: 2020

    Journal: Appl. Mater. Today, Volume 19, JUN

    Authors: Tu, Qiufen; Zhao, Xin; Liu, Shuai; Li, Xiangyang; Zhang, Qiang; Yu, Han; Xiong, Kaiqin; Huang, Nan; Yang, Zhilu

    Keywords: Cardiovascular stents; Biomimetic multi-functional coating; Spatiotemporal dual-delivery; Vascular endothelial growth factor; Nitric oxide

    Injury of endothelium is an inevitable consequence of cardiovascular stent implantation, which increases the incidence of in-stent restenosis (ISR) and late stent thrombosis (LST). Rapid and complete re- endothelialization, along with long-term suppression of smooth muscle cells (SMCs) are mandatory to alleviate these complications. To this goal, we designed a multi-functional stent coating, consisting of a vascular endothelial growth factor/Cu II-dopamine(VEGF/Cu II-DA) complex network for a spatiotempo- ral delivery of VEGF and nitric oxide (NO). We fabricated such network using a two-step stent-coating process: first a Cu II-DA network with NO catalytic activity via metal-catecholamine coordination chem- istry, followed by conjugation of VEGF onto the Cu II-DA network via imine formation. The conjugated VEGF significantly accelerated the early-stage endothelial cell (EC) migration/growth for the first 7 days, forming a new and complete endothelial layer on the lumen. Furthermore, Cu ions sustainably decom- posed endogenous S-nitrosothiols (RSNOs) in the bloodstream into NO for over 30 days, suppressing SMC migration/proliferation and ultimately preventing ISR and LST. Altogether, such designed stent coating provides options for a phase-adjusted endothelial repair during cardiovascular treatment. (C) 2019 Elsevier Ltd. All rights reserved.
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