Acteoside-Loaded Self-Healing Hydrogel Enhances Skin Wound Healing through Modulation of Hair Follicle Stem Cells.

BACKGROUND: Skin wound healing is a complex biological process involving cellular, molecular, and physiological events. Traditional treatments often fail to provide optimal outcomes, particularly for chronic wounds. OBJECTIVES: This study aimed to develop a self-healing hydrogel loaded with Acteoside, a bioactive compound with antioxidant and anti-inflammatory properties, to enhance skin wound healing. METHODS: Using transcriptomic analysis, Rab31 was identified as a key target of Acteoside in regulating hair follicle stem cells (HFSCs). In vitro assays demonstrated that Acteoside promotes HFSC proliferation, migration, and differentiation by upregulating Rab31 expression. The self-healing hydrogel was prepared using quaternized chitosan derivatives, which exhibited excellent mechanical properties, antibacterial, and antioxidant activities. RESULTS: In vivo studies in a mouse model showed that Acteoside-loaded hydrogel significantly accelerated wound healing, promoting skin regeneration and improving wound closure. CONCLUSIONS: This research highlights the potential of Acteoside-loaded self-healing hydrogels as an innovative therapeutic strategy for enhancing skin wound healing. By modulating HFSC activity, this hydrogel offers a promising solution for improving healing outcomes in challenging wound environments. GRAPHICAL ABSTRACT: Schematic representation of an injectable self-healing hydrogel loaded with the phenylethanoid compound acteoside for regulating the proliferation and differentiation of HFSCs to mediate the healing of skin wounds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-025-00845-2.