Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China; The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China.
Dongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong 523000, China; Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Guangzhou, Guangdong, China.
Biomaterials. 2023 Nov;302:122311. doi: 10.1016/j.biomaterials.2023.122311. Epub 2023 Aug 31.
Stenting is the primary treatment for vascular obstruction-related cardiovascular diseases, but it inevitably causes endothelial injury which may lead to severe thrombosis and restenosis. Maintaining nitric oxide (NO, a vasoactive mediator) production and grafting endothelial glycocalyx such as heparin (Hep) onto the surface of cardiovascular stents could effectively reconstruct the damaged endothelium. However, insufficient endogenous NO donors may impede NO catalytic generation and fail to sustain cardiovascular homeostasis. Here, a dopamine-copper (DA-Cu) network-based coating armed with NO precursor L-arginine (Arg) and Hep (DA-Cu-Arg-Hep) is prepared using an organic solvent-free dipping technique to form a nanometer-thin coating onto the cardiovascular stents. The DA-Cu network adheres tightly to the surface of stents and confers excellent NO catalytic activity in the presence of endogenous NO donors. The immobilized Arg functions as a NO fuel to generate NO via endothelial nitric oxide synthase (eNOS), while Hep works as eNOS booster to increase the level of eNOS to decompose Arg into NO, ensuring a sufficient supply of NO even when endogenous donors are insufficient. The synergistic interaction between Cu and Arg is analogous to a gas station to fuel NO production to compensate for the insufficient endogenous NO donor in vivo. Consequently, it promotes the reconstruction of natural endothelium, inhibits smooth muscle cell (SMC) migration, and suppresses cascading platelet adhesion, preventing stent thrombosis and restenosis. We anticipate that our DA-Cu-Arg-Hep coating will improve the quality of life of cardiovascular patients through improved surgical follow-up, increased safety, and decreased medication, as well as revitalize the stenting industry through durable designs.
支架置入术是治疗血管阻塞相关心血管疾病的主要方法，但它不可避免地会导致内皮损伤，从而可能导致严重的血栓形成和再狭窄。维持一氧化氮（NO，一种血管活性介质）的产生并将肝素（Hep）等内皮糖萼接枝到心血管支架表面，可以有效地重建受损的内皮细胞。然而，内源性一氧化氮供体不足可能会阻碍 NO 的催化生成，无法维持心血管内环境的稳定。在这里，我们使用无有机溶剂的浸渍技术制备了一种基于多巴胺-铜（DA-Cu）网络的涂层，该涂层携带一氧化氮前体 L-精氨酸（Arg）和 Hep（DA-Cu-Arg-Hep），可在心血管支架表面形成纳米级薄涂层。DA-Cu 网络紧密地附着在支架表面，并在存在内源性 NO 供体的情况下赋予优异的 NO 催化活性。固定化的 Arg 作为 NO 燃料，通过内皮型一氧化氮合酶（eNOS）生成 NO，而 Hep 作为 eNOS 增强剂，增加 eNOS 的水平，将 Arg 分解为 NO，从而确保即使内源性供体不足，也能提供足够的 NO。Cu 和 Arg 之间的协同相互作用类似于一个加油站，为 NO 生成提供燃料，以补偿体内内源性 NO 供体的不足。因此，它促进了天然内皮的重建，抑制了平滑肌细胞（SMC）的迁移，并抑制了血小板的级联黏附，从而防止了支架内血栓形成和再狭窄。我们预计，我们的 DA-Cu-Arg-Hep 涂层将通过改善手术随访、提高安全性、减少药物治疗来提高心血管患者的生活质量，并通过持久的设计来振兴支架行业。
