Liang Xiaoyang, Chen Honggui, Zhang Rui, Xu Zhixuan, Zhang Guo, Xu Chen, Li Yang, Zhang Lei, Xu Fu-Jian
State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
Biomaterials. 2025 Jun;317:123076. doi: 10.1016/j.biomaterials.2024.123076. Epub 2024 Dec 30.
Persistent inflammation is a major cause of diabetic wounds that are difficult to heal. This is manifested in diabetic wounds with excessive reactive oxygen clusters (ROS), advanced glycation end products (AGE) and other inflammatory factors, and difficulty in polarizing macrophages toward inhibiting inflammation. Berberine is a natural plant molecule that inhibits inflammation; however, its low solubility limits its biological function through cytosis. In this study, we designed F127 micelles to encapsulate berberine with the aim of improving its solubility and bioavailability. Meanwhile, in order to achieve effective drug delivery at the wound site, we designed an injectable ferrocene-cyclodextrin self-assembled oxidation-reactive supramolecular hydrogel drug delivery system. Cellular experiments have shown that the hydrogel can reduce intracellular ROS and AGE production, attenuate cellular damage, promote macrophage polarization toward inhibition of inflammation, and reduce the secretion of inflammatory factors. In an animal model of diabetic mice, this hydrogel dressing reduces the level of inflammation in diabetic wounds, optimizes collagen deposition in diabetic wounds, and ultimately achieves high-quality diabetic wound healing. The work offers a straightforward and effective solution to the challenge of administering hydrophobic anti-inflammatory agents in the context of diabetic wound therapy.
持续性炎症是糖尿病伤口难以愈合的主要原因。这表现为糖尿病伤口中存在过量的活性氧簇（ROS）、晚期糖基化终产物（AGE）和其他炎症因子，并且巨噬细胞难以向抑制炎症的方向极化。黄连素是一种抑制炎症的天然植物分子；然而，其低溶解度通过胞吞作用限制了其生物学功能。在本研究中，我们设计了F127胶束来包裹黄连素，目的是提高其溶解度和生物利用度。同时，为了在伤口部位实现有效的药物递送，我们设计了一种可注射的二茂铁 - 环糊精自组装氧化反应性超分子水凝胶药物递送系统。细胞实验表明，该水凝胶可减少细胞内ROS和AGE的产生，减轻细胞损伤，促进巨噬细胞向抑制炎症的方向极化，并减少炎症因子的分泌。在糖尿病小鼠动物模型中，这种水凝胶敷料降低了糖尿病伤口的炎症水平，优化了糖尿病伤口中的胶原蛋白沉积，并最终实现了高质量的糖尿病伤口愈合。这项工作为糖尿病伤口治疗中疏水性抗炎药物给药的挑战提供了一种直接有效的解决方案。
