Highly Deformable Organic Heterojunctions Empower Piezoelectric‐Conductive Hydrogels for Functional Volumetric Muscle Regeneration

ABSTRACT Volumetric muscle loss (VML) results in irreversible muscle impairment, necessitating tissue‐matched electrostimulation scaffolds for clinical repair. Here, we report a biointegrated hydrogel that leverages a piezoelectric‐conductive organic heterojunction to deliver self‐powered electrical cues directly to the injury site. The heterojunction comprises a piezoelectric metal–organic framework (MOF) coated with conductive polypyrrole (PPy), forming a stable p–n organic heterojunction with an intrinsic built‐in electric field. Unlike inorganic piezoelectrics, the organic MOF‐PPy features an ultralow elastic modulus, porous architecture, and exceptional deformability, delivering robust piezoelectric output under mild muscular contraction. These MOF‐PPy is then covalently integrated into a silk fibroin network via in situ photopolymerization to produce the MOF‐PPy@Sil hydrogel, where covalent conjugation ensures efficient stress transfer, maximizing piezoelectric signal generation. The piezoelectric and conductive cues significantly promote cell viability and migration, upregulate myogenic markers, and enhance maturation of organized muscle fibers. In a rat tibialis anterior VML model, MOF‐PPy@Sil drives myofiber formation, structural reconstruction, and near‐complete restoration of hindlimb motor function. Mechanistically, the endogenous electroactive niche upregulates myogenic and metabolic pathways, while mitigating inflammatory responses that impede muscle regeneration. This work presents a piezoelectric‐conductive hydrogel paradigm that harnesses the deformability of organic heterojunctions to generate a mechano‐electrical microenvironment for regenerative medicine.