Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6 macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6 macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect–cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.

中文翻译：

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ROS 响应性喷雾水凝胶作为 ROS 清除剂和 GATA6+ 巨噬细胞陷阱，用于预防术后腹部粘连

术后腹部粘连是手术后常见的临床问题，可引起许多严重的并发症。目前最常用的防粘连产品由于停留时间短且主要侧重于屏障功能，因此效果较差。在此，我们开发了一种可喷雾水凝胶屏障（sHA-ADH/OHA-E），具有基于创伤部位ROS水平的自我调节药物释放，作为智能炎症微环境调节剂和GATA6巨噬细胞陷阱，用于非粘附恢复腹部手术。合成了用己二酰肼修饰的磺化透明质酸（HA）缀合物（sHA-ADH），以及通过ROS可裂解硼酸酯键（OHA-E）接枝有表没食子儿茶素-3-没食子酸酯（EGCG）的氧化HA缀合物。通过简单地混合 sHA-ADH 和 OHA-E，通过形成动态共价酰腙，在 5 秒内即可轻松制备 sHA-ADH/OHA-E 水凝胶。 sHA-ADH/OHA-E水凝胶具有良好的生物相容性、适当的机械强度、可调的剪切稀化、自修复、不对称粘附以及合理的体内保留时间，满足完美物理屏障的要求。有趣的是，磺酸基赋予水凝胶令人满意的抗成纤维细胞和巨噬细胞附着能力，并首次被证明可以作为聚阴离子陷阱来防止 GATA6 巨噬细胞聚集。重要的是，EGCG 可以通过 ROS 触发智能释放，以减轻氧化应激并促进促炎性 M1 巨噬细胞极化为抗炎性 M2 表型。此外，恢复纤溶系统平衡以减少纤维化。由于上述优点，sHA-ADH/OHA-E水凝胶在大鼠侧壁缺损-盲肠磨损模型中表现出优异的抗粘连效果，有望成为一种有前景的、可临床转化的抗粘连屏障。