Pae/exo@PF-127 promote diabetic wound healing through miR-424–5p

作者：Yidan Xia, Beibei Han, Feng‐Yuan Zhang, Qirong Li, Qiang Feng, Shidong Zhang, Da Liu, Chao Lin, Dongxu Wang, Bin Liu · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156688 · 被引用次数：7 · 研究领域：Wound Healing and Treatments、Extracellular vesicles in disease、Pressure Ulcer Prevention and Management

BACKGROUND: Currently, chronic diabetic wound healing is one of the urgent clinical challenges. Choosing appropriate dressings loaded with stem cell-derived exosomes (exo) and traditional Chinese medicine extracts that promote healing is an effective method to accelerate skin healing in diabetes. Paeonol (Pae), possessing anti-inflammatory properties and vascular enhancement functions, can serve as a therapeutic herbal extract for treating diabetic wounds. METHODS: Exo were extracted from mesenchymal stem cells and loaded them with Pae (Pae/exo). The effects of Pae/exo on human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVEC) were evaluated using CCK-8, migration, and transwell assays. Western blotting, qPCR, and immunofluorescence experiments were conducted to analysis the regulation of associated genes and proteins. Mimics and inhibitors of miR-424-5p were synthesized to further investigate its role in HUVEC and HSF. Additionally, diabetic mice models were constructed with the knockout of miR-322 (a homologous miRNA of miR-424) to validate the impact of miR-424-5p knockout on diabetic skin healing in vivo. To better simulate clinical application, thermosensitive hydrogel Pluronic® F-127 (PF-127) was used as a carrier for Pae/exo, and the effect of Pae/exo@PF-127 on wound healing in diabetic mice was investigated. RESULTS: This study confirmed that Pae/exo increased the proliferation and migration of HSF and HUVEC by promoting epithelial-mesenchymal ...