Wang Yanan, Wu Haoshuang, Zhou Zhongyi, Maitz Manfred F, Liu Kunpeng, Zhang Bo, Yang Li, Luo Rifang, Wang Yunbing
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Dresden 01069, Germany.
Sci Adv. 2022 Mar 4;8(9):eabm3378. doi: 10.1126/sciadv.abm3378.
Interrelated coagulation and inflammation are impediments to endothelialization, a prerequisite for the long-term function of cardiovascular materials. Here, we proposed a self-regulating anticoagulant coating strategy combined with anti-inflammatory capacity, which consisted of thrombin-responsive nanogels with anticoagulant and anti-inflammatory components. As an anticoagulant, rivaroxaban was encapsulated in nanogels cross-linked by thrombin-cleavable peptide and released upon the trigger of environmental thrombin, blocking the further coagulation cascade. The superoxide dismutase mimetic Tempol imparted the antioxidant property. Polyphenol epigallocatechin gallate (EGCG), in addition to its anti-inflammatory function in synergy with Tempol, also acted as a weak cross-linker to stabilize the coating. The effectiveness and versatility of this coating were validated using two typical cardiovascular devices as models, biological valves and vascular stents. It was demonstrated that the coating worked as a precise strategy to resist coagulation and inflammation, escorted reendothelialization on the cardiovascular devices, and provided a new perspective for designing endothelium-like functional coatings.
相互关联的凝血和炎症是内皮化的障碍，而内皮化是心血管材料长期功能的先决条件。在此，我们提出了一种兼具抗炎能力的自调节抗凝涂层策略，该策略由具有抗凝和抗炎成分的凝血酶响应纳米凝胶组成。作为抗凝剂，利伐沙班被包裹在由凝血酶可裂解肽交联的纳米凝胶中，并在环境凝血酶触发时释放，从而阻断进一步的凝血级联反应。超氧化物歧化酶模拟物Tempol具有抗氧化性能。除了与Tempol协同发挥抗炎作用外，多酚表没食子儿茶素没食子酸酯（EGCG）还作为一种弱交联剂来稳定涂层。以生物瓣膜和血管支架这两种典型的心血管装置为模型，验证了该涂层的有效性和通用性。结果表明，该涂层是一种精确的抗凝血和抗炎策略，能促进心血管装置上的再内皮化，并为设计类内皮功能涂层提供了新的视角。
