After experiencing spinal cord injury (SCI), the interruption of electrical signal transmission impedes both nerve regeneration and functional recovery. Despite its potential as a treatment for spinal cord injury, intrathecal electrical stimulation (ES) is hindered by the risk of infection and the need for a subsequent operation to remove the tethered electrical interface, thereby severely limiting its effectiveness and clinical applicability. Herein, we constructed a conductive piezoelectric hydrogel (SFBP/PER) with ultrasound-triggered wireless ES capability and satisfied conductivity for SCI regeneration. The fabrication process involved the integration of perampanel and polypyrrole-modified BaTiO3 nanoparticles into silk fibroin, followed by enzymatic crosslinking at physiological temperature. We demonstrate that the SFBP/PER hydrogel exhibits anti-glutamate excitotoxicity and antioxidative capabilities in vitro. In vivo, experiments revealed that the SFBP/PER hydrogel significantly enhanced recovery of SCI rats by mitigating oxidative stress, apoptosis, and inflammation, reducing lesion cavities, enhancing remyelination, and promoting the regeneration of functional neurons. This study presents a novel approach utilizing a conductive piezoelectric hydrogel system for in vivo ES in tissue engineering applications.
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