Biomechanical and directional electric field coupling material promotes wound healing through Piezo1-mediated cell...

Re-epithelialization and extracellular matrix (ECM) regeneration determine the quality of wound repair. Although the physical microenvironment regulates these processes through physio-biochemical coupling, effective approaches are lacking. This study aims to reconstruct biomechanical and electric field microenvironments in wounds and is the first to develop a biomimetic coupling material that modulates wound mechanics and directional electric fields. The coupling material markedly accelerated re-epithelialization and promoted the ordered regeneration and structural remodeling of the ECM. Both axolotl skin-inspired biomechanical materials and application of electric fields at physiological intensities downregulated the expression of the mechanosensitive ion channel Piezo1 in keratinocytes, relieving its inhibitory effect on cell migration. This represents a new mechanism by which a biomimetic material with biomechanical and directional electric field coupling synergistically promotes keratinocyte migration. This study provides a novel strategy with translational potential for wound healing while offering theoretical insights and a versatile platform for research on wound regeneration.