Abstract The impairment of regenerative processes induced by high blood-glucose level (hyperglycemia) and excessive reactive oxygen species (ROS) contributes to the diabetic complication progression and development. In this study, an injectable, in situ crosslinkable chitosan hydrogel with ROS-scavenging capability was developed by conjugating gallic acid onto the chitosan backbone (CGA). We hypothesized that gallic acid serves as both antioxidant and crosslinking moieties to form hydrogel in situ by means of enzymatic crosslinking with horseradish peroxidase (HRP). The rapid gelation (from 30 s) was observed by vial tilting. The mechanical properties and microstructures of CGA hydrogels can be well controlled by varying the concentrations of H2O2. The ROS-scavenging ability of these CGA hydrogels was demonstrated against DPPH radical, hydroxyl radical, and total reducing power. Notably, in an in vitro hyperglycemia environment, CGA hydrogels significantly improved the proliferation and migration of human dermal fibroblast cells, which are closely related to diabetic wound healing. These results suggest that CGA hydrogels have potential as advanced materials for the treatment of diabetes-related diseases via attenuating the excessive ROS production and improving cellular behaviors.

中文翻译：

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具有自由基清除特性的新型酶交联壳聚糖水凝胶可促进高血糖下的细胞行为

摘要 由高血糖水平（高血糖）和过量活性氧 (ROS) 引起的再生过程受损有助于糖尿病并发症的进展和发展。在这项研究中，通过将没食子酸结合到壳聚糖骨架 (CGA) 上，开发了一种具有 ROS 清除能力的可注射、原位可交联壳聚糖水凝胶。我们假设没食子酸作为抗氧化剂和交联部分，通过与辣根过氧化物酶 (HRP) 的酶促交联原位形成水凝胶。通过小瓶倾斜观察到快速凝胶化（从 30 秒开始）。CGA 水凝胶的机械性能和微观结构可以通过改变 H2O2 的浓度来很好地控制。这些 CGA 水凝胶的 ROS 清除能力被证明可以对抗 DPPH 自由基，羟基自由基和总还原能力。值得注意的是，在体外高血糖环境中，CGA水凝胶显着改善了与糖尿病伤口愈合密切相关的人真皮成纤维细胞的增殖和迁移。这些结果表明，CGA 水凝胶通过减弱过量的 ROS 产生和改善细胞行为，具有作为治疗糖尿病相关疾病的先进材料的潜力。