Piezo-Nanowired Stem Cells: Ultrasound-Powered Neuronal Commitment for Rapid Neural Circuit Reconstruction after Traumatic Brain Injury.

The inherently constrained regenerative capacity of neuronal tissue poses a major obstacle to repairing traumatic brain injury. While neural stem cell transplantation holds promise, its efficacy is constrained by slow and inefficient neuronal differentiation. Here, we engineered piezo-nanowired stem cells by anchoring piezoelectric barium titanate nanowires to neural stem cell membranes, enabling ultrasound-powered piezoelectrical stimulation to drive neuronal differentiation. The high-aspect-ratio barium titanate nanowires stably localize on cell membranes, enabling targeted electrical stimulation to membrane-bound receptors under ultrasound. In vitro, this approach accelerated neuronal differentiation by 5 days, increasing the mature neuron ratio from 14.0% to 30.7%, and enhancing synaptic network complexity. In a traumatic brain injury rat model, barium titanate nanowires combined with ultrasound promoted rapid neural stem cells differentiation into functional neurons, restoring motor and cognitive functions and reconstructing neural networks at the injury site. By integrating wireless piezoelectric stimulation with neural stem cell transplantation, this work provides a promising approach for precise neuromodulation in neurological regeneration.