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

Intraprocedural endothelial cell seeding of arterial stents via biotin/avidin targeting mitigates in-stent restenosis.
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DOI:
10.1038/s41598-022-23820-7
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发表时间:
2022-11-10
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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血管内支架内皮化受损已被确定为支架内再狭窄和晚期支架血栓形成的主要原因。试图通过在植入前体外预先植入内皮细胞来增强支架内表面的内皮化,但在高压支架部署过程中细胞破坏而受到损害。在此,我们报道了一种新的支架内皮化策略,即将生物素修饰的内皮细胞植入到亲和素功能支架中。通过连续使用双膦酸聚烯丙胺、胺反应性生物素化试剂和亲和素对裸金属支架(BMS)进行处理,在支架表面获得亲和素单层。生物素修饰的内皮细胞保留了正常内皮细胞的生长特征,并能表达报告基因。在生理剪切条件下,与裸金属相比,附着在亲和素修饰的金属表面的再循环生物素化细胞数量高出50倍。将生物素化的内皮细胞递送到大鼠颈动脉段,其中含有植入的亲和素修饰支架,结果细胞立即与支架支柱结合,与BMS相比,支架内再狭窄减少30%。
Impaired endothelialization of endovascular stents has been established as a major cause of in-stent restenosis and late stent thrombosis. 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 containing 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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