National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China.
J Control Release. 2020 May 10;321:59-70. doi: 10.1016/j.jconrel.2020.02.002. Epub 2020 Feb 5.
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.
植入血接触材料/装置通常会引起严重的血栓形成、炎症反应、过度增生，最终导致内皮功能障碍。在这项工作中，通过构建一种基于儿茶酚介导和铜整合的多层涂层，建立了一种仿生方法来解决这些不良问题。仿生学主要通过两条途径获得。第一条是结构仿生学，它使用聚电解质（肝素和聚乙烯亚胺）来修饰儿茶酚基团，然后通过层层组装进一步形成多层涂层，以模拟贻贝粘合剂 DOPA 丰富的结构；第二条是功能仿生学，将铜离子整合到功能中，作为催化剂将内源性 S-亚硝基硫醇分解为释放一氧化氮（NO），以模拟健康内皮细胞的关键功能。石英晶体微天平（QCM-D）用于监测多层构建过程，并证明了儿茶酚介导的多层涂层的增强稳定性。此外，富含儿茶酚的涂层还可以支持肝素的持续释放。铜离子通过儿茶酚-Cu 配位整合到多层涂层中，并可以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形成和抗增生能力。用于血液灌注测试的体外动静脉（AV）分流模型和血管内金属丝植入进一步证明了该潜在用于血接触装置的仿生功能的高度仿生功能。
