Electrical stimulation mediated by poly(ε-caprolactone)/gelatin/Ti3C2TxMXene fibrous membranes enhances the paracrine function of adipose-derived stem cells and promotes wound repair

Current research primarily focuses on the effects of conductive fibrous membranes mediated electrical stimulation (ES) on stem cell behaviors. The role and mechanism of conductive fibrous membranes-mediated ES in regulating the paracrine function of adipose-derived stem cells (ADSCs) for tissue repair remain unexplored. This study aims to investigate the impact of ES mediated by poly (ε-caprolactone)/gelatin/Ti 3 C 2 T x MXene (PGM) fibrous membranes on the paracrine function of ADSCs. Our findings demonstrated that ES mediated by PGM fibrous membranes promoted the adhesion, spreading, proliferation, and migration of ADSCs. Furthermore, ES significantly enhanced the secretion of immunomodulatory and angiogenesis-related genes ( e.g. , hepatocyte growth factor (HGF) and transforming growth factor-β (TGF-β) and proteins ( e.g. , HGF and TGF-β) in the paracrine of ADSCs. Notably, the PGM@ES-CM group exhibited the highest secretion levels of factors promoting macrophage polarization and pro-angiogenic activity, with these secreted factors demonstrating functional efficacy in vitro assays and therapeutic potential in a full-thickness skin defect model. Mechanistically, the focal adhesion kinase (FAK)/extracellular-signal-regulated kinase (ERK) signaling pathway has been identified as a key regulatory pathway underlying ES-mediated modulation of paracrine function. Furthermore, an increase in intracellular Ca 2+ concentration, which mediated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, serves as another critical regulatory mechanism in the ES-mediated modulation of paracrine function. This study provides novel insights into developing advanced wound dressings that leverage biomaterial-mediated electrical signaling to orchestrate stem cell paracrine activity for tissue regeneration.