Inflammation-directed nanozyme-eluting hydrogel coating promotes vascular tissue repair by restoring reactive oxygen species homeostasis
Inflammation-directed nanozyme-eluting hydrogel coating promotes vascular tissue repair by restoring reactive oxygen species homeostasis
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DOI：
10.1016/j.cej.2022.140556
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发表时间：
2022-11-24
影响因子：
15.1
通讯作者：
Wang，Yunbing
中科院分区：
文献类型：
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作者：
Yang，Fan;Guo，Gaoyang;Wang，Yunbing
血栓形成和狭窄仍然是血管植入物的两种最常见的并发症。临床上抑制狭窄的最有效策略是基于抗增生药物如西罗莫司和依维莫司的洗脱，同时已知其也阻碍血管愈合和再生。选择性抑制内膜增生和促进内皮化仍然是血管植入物的高度挑战性目标。纳米氧化铈作为一种纳米酶，由于其自身再生的抗氧化活性，在炎症相关疾病的治疗中被广泛用于调节氧化应激。然而，纳米酶在血管植入物中的应用迄今未见报道。在这项研究中，我们构建了一种活性氧（ROS）靶向纳米氧化物洗脱的可降解两性离子水凝胶涂层膜覆膜支架具有良好的抗凝，促内皮化和免疫调节性能。水凝胶涂层具有良好的血液相容性，同时促进内皮细胞的生长。包埋在水凝胶中的纳米氧化铈可响应基质金属蛋白酶（MMP）释放，并通过模拟天然超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性，有效抑制人工和细胞内的活性氧。此外，纳米二氧化铈的掺入增加了巨噬细胞中抗炎细胞因子和生长因子的表达水平，并降低了促炎细胞因子的表达水平，诱导巨噬细胞表型从M1转换为M2。基于纳米酶整合水凝胶涂层PLLA膜的覆膜支架在植入兔髂动脉/腹主动脉后显示出较高的通畅率和轻微的内膜增生程度。这种先进的水凝胶涂层可能会提供一种新的低成本且无药物的策略，用于有效抑制血管狭窄并促进血管修复。
Thrombosis and stenosis remain two of the most prevalent complications of vascular implants. The most effective strategy in clinics to inhibit stenosis is based on the eluting of anti-hyperplasia drugs such as sirolimus and everolimus while it also has been known to hinder vascular healing and regeneration. Selectively inhibiting intimal hyperplasia and promoting endothelialization remains a highly challenging target for vascular implants. Due to auto-regenerative antioxidant activity nanoceria as a nanozyme has been widely used to regulate oxidative stress in the treatment of inflammation-related diseases. Yet the application of nanozyme in vascular implants has not hitherto been reported. In this study we constructed a reactive oxygen species (ROS)-targeted nanoceria-eluting degradable zwitterion hydrogel coating on membrane-covered stents with favorable anti-coagulation pro-endothelialization and immunomodulation properties. The hydrogel coating exhibited excellent hemocompatibility and simultaneously promoted the growth of endothelial cells. Nanoceria embedded in hydrogel could be released in response to matrix metalloproteinase (MMP) and effectively scavenge artificial and intracellular ROS via mimicking the activity of natural superoxide dismutase (SOD) and catalase (CAT). In addition the incorporation of nanoceria increased the expression levels of anti-inflammation cytokines and growth factors and reduced the expression levels of pro-inflammation cytokines in macrophages inducing a switch of macrophage phenotype from M1 to M2. The membrane-covered stent based on nanozyme-integrated hydrogel-coated PLLA membrane exhibited a high patency rate and slight intima hyperplasia degree upon implantation into rabbits' iliac arteries/abdominal aortas. This advanced hydrogel coating may provide a new low-cost and drug-free strategy for effectively inhibiting vascular stenosis and promoting vascular repair.