Self-Assembled Platelet-Derived Growth Factor-Mimetic Peptide@BG Hydrogel Promotes Wound Healing by Regulating Mitochondrial Function through the RhoA/Rock1/Drp1 Signaling Axis

Skin wound healing involves four overlapping phases, with angiogenesis and mitochondrial functional recovery being critical for effective repair. In this study, a platelet-derived growth factor (PDGF)-mimetic peptide hydrogel was constructed and combined with bioactive glass to form a PDGF-mimetic peptide@BG composite system, aiming to synergistically promote wound healing. The structural stability and morphology of the PDGF-mimetic peptide@BG were characterized using electron microscopy and spectroscopic techniques. Biocompatibility was assessed through in vitro cell experiments. A full-thickness skin defect model in mice was established, and wound healing, angiogenesis, and mitochondrial functional recovery were evaluated using histological staining, Western blotting, and immunofluorescence. The involvement of the RhoA/Rock1/Drp1 signaling pathway in mitochondrial function improvement was investigated. The PDGF-mimetic peptide@BG was successfully prepared with stable structure. In vitro experiments demonstrated good biocompatibility and promotion of endothelial cell proliferation and migration. In vivo results confirmed that PDGF-mimetic peptide@BG accelerated wound healing in mice, enhanced granulation tissue formation and collagen deposition, and increased local blood flow and angiogenesis. Furthermore, the composite restored mitochondrial function, as evidenced by reduced ROS levels, elevated ATP and SOD activity, improved mitochondrial morphology, and downregulation of mitochondrial fission-related proteins. Mechanistic studies suggested that PDGF-mimetic peptide@BG may exert its reparative effects at least in part through inhibition of the RhoA/Rock1/Drp1 signaling pathway. This study suggests that the PDGF-mimetic peptide@BG significantly promotes tissue regeneration in a normal murine wound model by increasing wound blood flow, enhancing vascularization, accelerating mitochondrial repair, and improving its structure and function. These findings provide a preliminary foundation for further evaluation in clinically relevant impaired-healing models.