Motion-driven piezoelectric response in self-powered hydrogel nanofibers enhances wound healing via intermediate filament remodeling and modulation of energy metabolism

Metabolic regulation is essential for tissue homeostasis and for competence to activate the repair process in damaged tissue. Considering that bioelectric signals possess the ability to regulate cellular membrane potential and cellular energy metabolism for cell activation and skin physiological homeostasis, this study introduces a biomimetic, self-powered piezoelectric hydrogel nanofiber platform to reconstruct the bioelectrical microenvironment and offers a collagen fiber-like structure and antioxidant/anti-inflammatory properties to support intermediate filament remodeling and energy metabolism intervention for therapeutic advances in severe wound repair. Results demonstrate the successful fabrication of the collagen fiber-like substrate through the combination of electrospinning and photo-crosslinking of gelatin methacryloyl. Afterwards, the incorporation of tetragonal barium titanate nanoparticles significantly endows the substrate with notable piezoelectric properties, while tannic acid (TA) modification effectively mitigates the severe inflammatory microenvironment. When implanted in a rat model of dorsal skin injury, the piezoelectric hydrogel nanofibers are noted to markedly promote epidermal regeneration and accelerate skin wound healing. Transcriptome analysis reveals the mechanisms by which the TA-modified biomimetic hydrogel nanofibers enhance cell recruitment through cytokine-cytokine receptor interaction pathways and accelerate skin repair via immune response regulation. Furthermore, piezoelectric stimulation facilitates skin regeneration by activating linoleic acid-related metabolisms, preventing skin aging through the estrogen signaling pathway, and suppressing skin fibrosis by regulating the remodeling of motor protein-mediated contractile cytoskeleton. Overall, this work is poised to advance the development of bioelectricity-induced wound dressings, opening a new avenue for the management of severe skin wounds.