An implantable mechano-electro cascade platform synchronizes neuro-muscle repair

Peripheral nerve injury triggers slow axonal regeneration and irreversible muscle atrophy due to the absence of synchronous neuromuscular repair strategies. We present a fully implantable, self-powered Mechano-driven Electro-adaptable Bioelectronic Implant System (MEBIS) enabling coordinated mechanical-electrical stimulation for integrated neuromuscular regeneration. A programmable robotic actuator delivers quantifiable mechanical massage to denervated muscle, enhancing perfusion while deforming a nanogenerator that converts motion into localized electrical cues. These signals stimulate injured nerves, inducing intracellular Ca²⁺ elevation and Ca²⁺-dependent signaling, which activates downstream HIF-1α/AMPK pathways to accelerate Schwann cell activity, angiogenesis, and axonal regrowth. This mechano-electro-biochemical cascade couples muscle preservation with nerve regeneration in a closed loop, overcoming depth limitations and output instability of conventional stimulators. Validated in rat and porcine models, MEBIS significantly improves functional recovery, electrophysiology, and histomorphometry without biocompatibility concerns. Our platform establishes a scalable, feedback-controlled paradigm for precision repair and rehabilitation after peripheral nerve injury.