Piezoelectric film promotes skin wound healing with enhanced collagen deposition and vessels regeneration via upregulation of PI3K/AKT

Skin wounds are common in accidental injuries, and the intricacies of wound repair are closely linked to endogenous electric fields. Electrical stimulation plays a pivotal role in the restorative processes of skin injuries, encompassing collagen deposition, angiogenesis, inflammation, and re-epithelialization. Employing electrical stimulation therapy replicates and enhances the effects of endogenous wound electric fields by applying an external electric field to the wound site, thereby promoting skin wound healing. In this study, we developed a self-powered repetitive mechanical impacts-electrical stimulation (RMI-ES) system utilizing a BaTiO3/polydimethylsiloxane (PDMS) piezoelectric composite film. Compared to conventional electrical stimulation devices, the fabricated piezoelectric composite film efficiently harvests energy from the pressure applied by the stimulation device and the tensile force occurring during natural rat activities. The results demonstrated that piezoelectric stimulation generated by the composite membrane expedited the cell cycle, promoting fibroblast proliferation. Additionally, piezoelectric stimulation induced favorable changes in fibroblast gene expression, including increased expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen 1, collagen 3, vascular endothelial growth factor (VEGF), and alpha-smooth muscle actin (α-SMA), while reducing interleukin-6 (IL-6) expression. Transcriptome analysis revealed that piezoelectric stimulation may induce fibroblast migration, proliferation, and collagen expression by influencing PI3K/AKT serine/threonine kinase (AKT) pathways. Further confirmation through the addition of the PI3K inhibitor LY294002 validated that piezoelectric stimulation can regulate the repair process after skin injury through the pathway. Importantly, in vivo results demonstrated that the electric field at the wound site effectively promoted wound healing, reduced inflammation, and stimulated collagen deposition and neovascularization. This study emphasizes the role of the piezoelectric membrane as an effective, safe, and battery-free electrical stimulator crucial for skin wound healing.