Spatiotemporal Self‐Driven Biomimetic Myoelectric Hydrogel for Efficient Repair of Volumetric Muscle Loss

ABSTRACT Volumetric muscle loss (VML) repair remains fundamentally limited by the absence of spatiotemporally controllable bioelectrical signals, which impede coordinated structural regeneration and functional recovery. Herein, we engineer a self‐driven biomimetic myoelectric hydrogel by integrating piezoelectrically enhanced PLLA‐AgNW nanorods, a conductive CMCS‐PANI network, and an injectable tissue‐adhesive poly(α‐lipoic acid‐tannic acid) matrix. This design addresses conventional piezoelectric hydrogel bottlenecks, such as the inability to sustain a controllable electrical output under weak muscle contraction and poor spatial charge propagation into deep defects. In vitro, spatiotemporally coupled stimulation enhanced myoblast migration, myogenic differentiation (MyoD1/MHC), and pro‐angiogenic signaling. In a rat tibialis anterior VML model, the hydrogel suppressed fibrosis while promoting neovascularization and myofiber regeneration, resulting in robust motor recovery. Transcriptomic and metabolomic analyses indicated the involvement of Piezo1/Ca 2+ ‐related signaling, cell‐matrix remodeling, and alterations in energy metabolism‐related pathways. This spatiotemporal electrostimulation strategy achieves seamless integration of structural, signal, and functional restoration, thereby establishing a new paradigm for the applications of electroactive biomaterials in complex soft tissue regeneration.