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Spatiotemporal dual-delivery of therapeutic gas and growth factor for prevention of vascular stent thrombosis and restenosis
Applied Materials Today ( IF 8.3 ) Pub Date : 2020-01-08 , DOI: 10.1016/j.apmt.2019.100546
Qiufen Tu , Xin Zhao , Shuai Liu , Xiangyang Li , Qiang Zhang , Han Yu , Kaiqin Xiong , Nan Huang , Zhilu Yang

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/CuII-dopamine(VEGF/CuII-DA) complex network for a spatiotemporal delivery of VEGF and nitric oxide (NO). We fabricated such network using a two-step stent-coating process: first a CuII-DA network with NO catalytic activity via metal-catecholamine coordination chemistry, followed by conjugation of VEGF onto the CuII-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 decomposed 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.



中文翻译:

时空双重输送治疗性气体和生长因子以预防血管支架血栓和再狭窄

内皮损伤是心血管支架植入术的必然结果,这会增加支架内再狭窄(ISR)和晚期支架血栓形成(LST)的发生率。快速而彻底的重新内皮化,以及长期抑制平滑肌细胞(SMC)是缓解这些并发症的强制性措施。为此,我们设计了一种多功能支架涂层,该涂层涂层由血管内皮生长因子/ Cu II-多巴胺(VEGF / Cu II -DA)复合网络组成,用于时空递送VEGF和一氧化氮(NO)。我们使用两步支架涂覆工艺制造了这种网络:首先通过金属-儿茶酚胺配位化学形成具有NO催化活性的Cu II -DA网络,然后将VEGF偶联到Cu上II-通过亚胺形成的-DA网络。在最初的7天中,缀合的VEGF显着加速了早期内皮细胞(EC)的迁移/生长,在管腔上形成了一个新的完整的内皮层。此外,Cu离子在超过30天的时间内可持续地将血流中的内源性S-亚硝基硫醇(RSNO)分解为NO,从而抑制SMC迁移/增殖并最终防止了ISR和LST。总而言之,这种设计的支架涂层为心血管治疗期间的相位调节的内皮修复提供了选择。

更新日期:2020-01-08
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