Runze Zhou, Zhihao Zhang, Epiphane K Silli, Tianchi Lu, Luyong Zhang, Ting Liu, Zhenhai Zhang, Gangli Wang, Huixia Lv
Cell-laden skin equivalents represent a promising approach for chronic wound repair; however, their therapeutic efficacy is limited by poor cell viability and high susceptibility to bacterial invasion. We report a multifunctional bilayer skin substitute that integrates a piezoelectric poly(L-lactic acid)/carbon nanotube (PLLA/CNT) electrospun membrane as an artificial epidermis with a conductive gelatin-hyaluronic acid methacryloyl (Gel-HAMA) hydrogel dermis encapsulating fibroblasts and protocatechualdehyde (PA). Under 6 Hz, 2 N stimulation, the membrane generated 0.8 V, while vibration produced representative outputs reaching 2.5 V. This stimulation induces piezocatalytic reactive oxygen species (ROS) production, achieving antibacterial activity against the tested Staphylococcus aureus, Escherichia coli, and methicillin-resistant S. aureus strains. The conductive hydrogel efficiently transmits bioelectric signals to encapsulated fibroblasts, while sustained PA release provides antioxidant protection and preserves cell viability under oxidative stress. Transcriptomic analysis combined with network pharmacology shows that synergistic electrical and biochemical cues activate HIF-1, MAPK, and FoxO pathways, enhancing fibroblast migration and collagen remodeling. In an infected diabetic wound model, the bilayer construct accelerates wound closure to 92.4% within 15 days, reduces IL-6 expression, and outperforms povidone-iodine in bacterial clearance. This self-powered bioelectronic platform integrates infection control with regenerative stimulation and offers a promising strategy for advanced chronic wound therapy.