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A robust mussel-inspired zwitterionic coating on biodegradable poly(L-lactide) stent with enhanced anticoagulant, anti-inflammatory, and anti-hyperplasia properties
Chemical Engineering Journal ( IF 13.3 ) Pub Date : 2021-06-19 , DOI: 10.1016/j.cej.2021.130910
Li Yang , Haoshuang Wu , Yuqi Liu , Qiongfen Xia , Yuan Yang , Nuoya Chen , Ming Yang , Rifang Luo , Gongyan Liu , Yunbing Wang

Endowing cardiovascular stents with multiple functionalities, such as anti–proliferative, and anti–inflammatory properties, is important for combating restenosis after stent implantation. The surface properties of stents play a key role in obtaining the desired post–implantation performance. Zwitterionic coatings are resistant to non–specific adsorption, and here, a mussel–inspired zwitterionic poly (carboxybetaine acrylate–co–dopamine methacrylate) copolymer (PCBDA) was synthesized and applied to the surface of a biodegradable poly(l–lactide) stent. To obtain a zwitterionic polymer coating, the surface of a PLA stent was pretreated by co–depositing polydopamine (PDA) and polyethyleneimine (PEI). The mussel–inspired catechol moieties in the PCBDA copolymer cross–linked with the PDA–PEI hybrid to form a robust PCBDA/PDA–PEI coating on the PLA stent. The zwitterionic PCBDA formed a hydration layer once it contacted blood, preventing the non–specific adsorption of serum proteins, which further blocked subsequent coagulation and inflammation. The anti–protein adsorption tests showed that the PCBDA/PDA–PEI coating resisted the non–specific adsorption of fibrinogen, which was a positive signal for enhanced anti–coagulation. Moreover, the platelet adhesion/activation tests confirmed its antithrombotic properties. The in vivo tissue response was also greatly suppressed due to the inhibited recognition of PCBDA/PDA–PEI–coated implants by macrophages. Interestingly, unlike traditional zwitterionic polymers, due to the introduction of adhesive catechol moieties, PCBDA supported the growth of endothelial cells, demonstrating its ability to selectively direct the fate of endothelial cells and smooth muscle cells. In vivo stent implantation results showed inhibited intimal hyperplasia due to the protection of PCBDA/PDA–PEI. Overall, due to the specific characteristics of the mussel–inspired PCBDA/PDA–PEI coating, anticoagulation, anti–inflammatory, and anti–proliferation properties were obtained; thus, it is expected that this coating can be used to inhibit restenosis and realize endothelialization after stent implantation.



中文翻译:

可生物降解聚(L-丙交酯)支架上的坚固的受贻贝启发的两性离子涂层,具有增强的抗凝、抗炎和抗增生特性

赋予心血管支架多种功能,例如抗增殖和抗炎特性,对于对抗支架植入后的再狭窄非常重要。支架的表面特性在获得所需的植入后性能方面起着关键作用。两性离子涂层具有抗非特异性吸附的能力,在这里,合成了一种受贻贝启发的两性离子聚(羧基甜菜碱丙烯酸酯-共-多巴胺甲基丙烯酸酯)共聚物(PCBDA)并将其应用于可生物降解的聚(l–丙交酯)支架。为了获得两性离子聚合物涂层,PLA支架的表面通过共沉积聚多巴胺(PDA)和聚乙烯亚胺(PEI)进行了预处理。PCBDA 共聚物中受贻贝启发的儿茶酚部分与 PDA-PEI 杂化物交联,在 PLA 支架上形成坚固的 PCBDA/PDA-PEI 涂层。两性离子 PCBDA 一旦接触血液就会形成水合层,防止血清蛋白的非特异性吸附,从而进一步阻止随后的凝血和炎症。抗蛋白吸附试验表明,PCBDA/PDA-PEI 涂层可抵抗纤维蛋白原的非特异性吸附,这是增强抗凝作用的阳性信号。此外,血小板粘附/活化测试证实了其抗血栓形成特性。在体内由于巨噬细胞对 PCBDA/PDA-PEI 涂层植入物的识别受到抑制,组织反应也受到极大抑制。有趣的是,与传统的两性离子聚合物不同,由于引入了粘附性儿茶酚部分,PCBDA 支持内皮细胞的生长,证明其能够选择性地指导内皮细胞和平滑肌细胞的命运。体内支架植入结果显示由于 PCBDA/PDA-PEI 的保护,内膜增生受到抑制。总体而言,由于受贻贝启发的 PCBDA/PDA-PEI 涂层的特定特性,获得了抗凝、抗炎和抗增殖特性;因此,预计该涂层可用于抑制支架植入后的再狭窄并实现内皮化。

更新日期:2021-06-30
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