Epigallocatechin gallate mediated sandwich-like coating for mimicking endothelium with sustained therapeutic nitric oxide generation and heparin release.
Epigallocatechin gallate mediated sandwich-like coating for mimicking endothelium with sustained therapeutic nitric oxide generation and heparin release.
复制标题
DOI：
10.1016/j.biomaterials.2020.120418
复制
发表时间：
2020-10
期刊：
影响因子：
14
通讯作者：
Bo Zhang;Ruijuan Yao;Chengxin Hu;M. Maitz;Haoshuang Wu;Kunpeng Liu;Li Yang;Rifang Luo;
中科院分区：
文献类型：
--
作者：
Bo Zhang;Ruijuan Yao;Chengxin Hu;M. Maitz;Haoshuang Wu;Kunpeng Liu;Li Yang;Rifang Luo;
支架置入后支架内再狭窄通常以炎症反应、平滑肌细胞过度增殖和内皮层愈合延迟为特征。本研究受儿茶酚/没食子酸酯表面化学的启发，以壳聚糖和肝素为聚电解质，包埋表没食子儿茶素没食子酸酯/铜（EGCG/Cu）复合物，开发了一种三明治状分层（LBL）涂层。EGCG的包埋通过在LBL涂层中的各种分子间相互作用（如π-π堆叠、弱分子间交联和丰富的氢键）来稳定涂层，并支持货物肝素在90天内的持续释放。在铜离子催化分解内源性s -亚硝基硫醇的作用下，该设计实现了肝素的持续释放和一氧化氮的持续生成的仿生内皮功能。结果显示抗凝持久性增强，炎症反应被抑制。此外，“三明治状”涂层支持内皮细胞的生长，上调血管内皮生长因子的蛋白表达，同时通过上调环鸟苷单磷酸有效抑制平滑肌细胞（SMCs）的增殖和迁移。体外和体内实验证明了三明治状涂层在防止血栓形成、抑制SMCs生长、减少炎症细胞的浸润和活化、最终实现快速原位内皮化方面的有效性。因此，egcg辅助的三明治状涂层可作为植入式心血管装置的一种强大且通用的表面改性策略。
In-stent restenosis after stenting is generally characterized by an inflammatory response, excessive proliferation of smooth muscle cells, and delayed healing of the endothelium layer. In this study, inspired by catechol/gallol surface chemistry, a sandwich-like layer-by-layer (LBL) coating was developed using chitosan and heparin as polyelectrolytes, along with the embedding of an epigallocatechin gallate/copper (EGCG/Cu) complex. The embedding of EGCG stabilized the coating by various intermolecular interactions in the LBL coating (e.g., π-π stacking, weak intermolecular crosslinking, and enriched hydrogen bonding) and supported the sustained release of the cargo heparin over 90 days. This design enabled a biomimetic endothelium function in terms of the sustained release of heparin and continuousin situgeneration of nitric oxide, driven by the catalytic decomposition of endogenous S-nitrostothiols by copper ions. The result showed enhanced durability of anticoagulation and suppressed inflammatory response. Moreover, the “sandwich-like” coating supported the growth of endothelial cells and up-regulated the protein expression of vascular endothelial growth factor, while effectively suppressing the proliferation and migration of smooth muscle cells (SMCs) via the up-regulation of cyclic guanosine monophosphate.Ex vivoand in vivo experiments demonstrated the effectiveness of the sandwich-like coating in preventing thrombosis formation, suppressing the growth of SMCs, reducing the infiltration and activation of inflammatory cells, and ultimately achieving rapidin situendothelialization. Hence, the EGCG-assisted sandwich-like coating might be used as a robust and versatile surface modification strategy for implantable cardiovascular devices.