Mesenchymal Stem Cell‐Driven Neurotrophic Bioelectronic Platform (MSC‐NBP) Potentiated Peripheral Nerve Regeneration

Abstract Peripheral nerve injury (PNI) causes persistent sensory and motor deficits, and current surgical repairs fail to fully restore function due to insufficient axonal regeneration, remyelination, and immune modulation. Mesenchymal stem cells (MSCs) offer neurotrophic and immunoregulatory benefits, but post‐transplant survival and activation are suboptimal. Electrical stimulation (ES) promotes axonal growth and myelination, yet as a stand‐alone intervention, ES delivers imprecise dosing, risks device‐related injury, and offers no biological support. Here, a Mesenchymal Stem Cell‐Driven Neurotrophic Bioelectronic Platform (MSC‐NBP) that integrates umbilical cord‐derived MSCs encapsulated in molybdenum nanoparticle‐doped GelMA conductive hydrogel with a skin‐activated, wireless ES device, is presented. The Gel/Mo scaffold provides injectability, rapid in situ crosslinking, tunable mechanics, and high conductivity to ensure stable ES dosing and intimate nerve interfacing. In vitro, ES reprogrammes MSCs toward Schwann cell‐like phenotypes, significantly enhancing secretion of BDNF, NGF, and IL‐10 and supporting neuronal axon elongation and activity. Single‐cell transcriptomics reveal upregulation of neuroregenerative pathways and strengthen MSC‐Schwann cell interactions. In vivo, MSC‐NBP achieves superior gait recovery, muscle preservation, electrophysiological improvement, and histological regeneration compared to single‐modality controls, with confirmed long‐term biosafety. This integrative bioelectronic‐cellular platform offers a mechanism‐driven and clinically translatable strategy for maximizing PNI repair.