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 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.