Magneto‐Motivated Intracellular Wireless Nanodischarge System Induces Neural Stem Cell Differentiation and Spinal Cord Injury Repair

Abstract While extracellular electrical stimulation for neural repair is established, intracellular electrostimulation remains underexplored. This study proposes an intracellular wireless nanodischarge (IWND) system that leverages electromagnetic induction, with endocytosed multishell gold nanoparticles (MS‐Au NPs) serving as electromagnetic dischargers inside neural stem cells (NSCs). An external rotating magnetic field (RMF) above the NSCs is employed as a transmitter to trigger an induced electric charge. In vitro, the IWND system accelerates neuronal differentiation, achieving a 5‐day advancement and enhancing the mature neuron yield from 15.9% to 49.8%, mainly cholinergic and dopaminergic phenotypes, which are pivotal neuronal populations governing motor coordination and cognitive function. Mechanistically, a moderate concentration of reactive oxygen species (ROS), originating from the electrocatalytic reactions based on wireless nanodischarge‐mediated electrogenesis, activates the extracellular signal‐related kinase (ERK) signaling cascade, forming a key signaling axis in IWND‐driven neural differentiation through controlled oxidative signaling. In vivo experiments demonstrate that transplantation of MS‐Au NP‐internalized NSCs in combination with external magnetic stimulation significantly restores motor function in mice with spinal cord injury, primarily through differentiation into functional neurons. This study establishes a platform for developing spatiotemporally precise stem cell therapies through intracellular bioelectrical modulation, offering new possibilities for neural circuit reconstruction in neurological disorders.