Triboelectric nanogenerator for modulating neuronal outgrowth and neuroplasticity through controlled stimulation

Electrical stimulation effectively accelerates rehabilitation but is limited by the reliance on external power sources or frequent battery replacements, reducing its practicality for long-term use. To address this limitation, triboelectric nanogenerators (TENGs) offer a self-powered alternative, converting human kinetic energy into electrical energy. Although promising in both in vitro and in vivo studies, TENG-based stimulation is constrained by insufficient current output, falling short of the milliampere range needed for effective stimulation. In this study, we developed a TENG system with periodic switching to overcome these limitations, achieving higher current output and reduced internal impedance. The TENG device was integrated with an agar salt bridge setup to deliver controlled electric field (EF) stimulation to neurons isolated from rat pup brains. Subthreshold EF stimulation and suprathreshold EF stimulation were systematically compared for their effects on neuronal outgrowth. Immunofluorescence analysis revealed that subthreshold stimulation primarily induced neurite sprouting, characterized by increased attachment points and initial elongation, whereas suprathreshold stimulation significantly enhanced neurite branching, morphological complexity, and synaptogenesis. These morphological trends were further supported by qPCR analysis, which demonstrated a dose-dependent upregulation of neuroplasticity-related genes, including those associated with neurite outgrowth. Together, these findings highlight the efficacy of TENG-based EF stimulation in promoting neuroplasticity and suggest its potential as a scalable, self-powered tool for facilitating neuronal recovery and rehabilitation following injuries.