Catechol-mediated and copper-incorporated multilayer coating: An endothelium-mimetic approach for blood-contacting devices
Catechol-mediated and copper-incorporated multilayer coating: An endothelium-mimetic approach for blood-contacting devices
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儿茶酚介导和铜掺入的多层涂层：用于血液接触装置的内皮模拟方法
DOI：
10.1016/j.jconrel.2020.02.002
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发表时间：
2020
影响因子：
10.8
通讯作者：
Wang Yunbing
中科院分区：
文献类型：
--
作者：
Yang Li;Li Linhua;Wu Haoshuang;Zhang Bo;Luo Rifang;Wang Yunbing
植入接触血液的材料/装置通常会导致严重的血栓形成、炎症反应、过度增生，最终导致内皮功能障碍。在这项工作中，建立了一种仿生的方法来解决这些不利的问题，通过构建邻苯二酚介导的和铜结合的多层涂层。仿生学主要通过两条途径获得。一种是结构仿生学，用聚电解质(肝素和聚乙烯亚胺)修饰邻苯二酚基团，然后通过层层组装形成多层涂层，模拟贻贝粘附剂DOPA的富含结构；第二种是功能仿生学，通过掺入铜离子作为催化剂，分解内源性的S-亚硫醇释放一氧化氮(NO)，从而模拟健康内皮细胞的关键功能。用耗散石英晶体微天平(QCM-D)监测了多层膜的构建过程，证明了邻苯二酚介导型多层膜的稳定性增强。此外，儿茶酚涂层还可以支持肝素的缓释。铜离子通过邻苯二酚-铜配位作用被引入到多层膜中，并能在生理水平上有效地原位生成NO。由于肝素的持续释放和持续的NO生成，获得了协同的抗血栓和抗增殖能力。用于血液灌流测试和血管内金属丝植入的体外动静脉分流模型进一步展示了血液接触器潜在的高仿生功能。
Implantation of blood-contacting materials/devices usually causes severe thrombus formation, inflammatory reactions, excessive hyperplasia, and ultimately, induce endothelial dysfunction. In this work, a biomimetic approach was established to address those adverse problems through constructing a catechol-mediated and copper-incorporated multilayer coating. The biomimetics was mainly obtained via two paths. The first one was structure bionics, which used polyelectrolytes (heparin and polyethyleneimine) to modify with catechol moieties and then further formed a multilayer coating via layer-by-layer assembly, so as to mimic the mussel adhesive DOPA-rich structure; the second one was function bionics, which copper ions were then incorporated to function as the catalysts to decompose the endogenous S-nitrosothiols to release nitric oxide (NO), so as to mimic the key function of healthy endothelial cells. The quartz crystal microbalance with dissipation (QCM-D) was used to monitor the multilayer construction process and demonstrated the enhanced stability of the catechol-mediated multilayer coatings. Besides, the catechol-rich coating could also support the sustained release of heparin. Copper ions were incorporated into the multilayer coatings via the catechol-Cu coordination, and could effectively generate NO in situ at a physiological level. Due to the sustained release of heparin and continuous NO generation, the synergistic antithrombogenicity and anti-hyperplasia ability were obtained. The ex-vivo arteriovenous (AV) shunt model for blood perfusion test and metal wire implantation in blood vessels further demonstrated the high biomimetic functionality of potential applications for blood-contacting devices.