4′-hydroxychalcone nanofiber hydrogel dressing promotes diabetic chronic wound healing by regulating macrophage polarization via the TLR/IL-17/TNF signaling pathway

作者：Hongyang Li, Min-Shan Li, Chuan-Xin Cui, Hongmei Yu, Yu Sun, Jijun Yang, Yaru Li, Yiquan Li, T Z Liu · 发表于：Materials Today Bio · 年份：2025 · DOI：10.1016/j.mtbio.2025.102474 · 被引用次数：6 · 研究领域：Wound Healing and Treatments、Immune cells in cancer、Signaling Pathways in Disease

Background: The activation and polarization of macrophages play a crucial role in the inflammatory response in chronic diabetic wound healing. Modulating macrophage polarization toward the M2 phenotype can facilitate wound healing. 4'-Hydroxychalcone (4HC) possesses antioxidant and anti-inflammatory properties, and the preparation of novel drugs through electrospun nanofibers and hydrogels can enhance its therapeutic effects. However, the effects of the 4'-hydroxychalcone nanofiber hydrogel dressing (P-4HC) prepared in this study on macrophage polarization and its potential mechanisms in the treatment of diabetic chronic wounds have not yet been elucidated. Objective: This study aimed to investigate the effect of P-4HC on macrophage polarization in diabetic chronic wounds and to elucidate its potential mechanisms of action. Methods: In vitro, cell compatibility tests were conducted using L929, HUVECs, and RAW264.7, along with ROS, scratch assays, tube formation assays, immunofluorescence tests for macrophage phenotypes, flow cytometry, and Western blotting (WB). In vivo, a diabetic mouse skin wound model was established, and HE and Masson staining, immunohistochemical staining of COL3A1, HIF-1a, and VEGF, immunofluorescence staining of CD31, CD86, and CD206, WB, RT-qPCR, and ELISA were conducted. Results: In vitro and in vivo, P-4HC exhibited good cell compatibility, improved tissue hypoxia, and promoted angiogenesis and collagen deposition. It promoted the transition of macr...