Ultrasound-triggered spinal cord-mimetic electroactive hydrogel enables localized bioelectrical modulation and promotes spinal cord injury repair through JNK-mediated autophagy.

Spinal cord injury (SCI) creates a hostile microenvironment that severely limits neural regeneration and functional recovery. Although bioelectrical modulation has emerged as a promising strategy for SCI repair, existing biomaterials generally provide either passive electrical conduction or stimulus-responsive electrical generation, but rarely integrate both properties within a mechanically compliant scaffold suitable for spinal cord repair. Here, we developed an injectable, remotely activatable electroactive hydrogel (SMT) by integrating conductive MXene nanosheets into a silk fibroin/tannic acid matrix, endowing the scaffold with tissue-matched mechanics, continuous electrical conductivity, and stimulus-responsive electrical output. Upon ultrasound activation, SMT generated localized bioelectrical cues within the lesion site. At the cellular level, SMT exhibited intrinsic antioxidant and anti-inflammatory effects that were further enhanced by ultrasound activation, while SMT + US promoted autophagic flux through Ca2+-dependent JNK signaling. In a rat model of SCI, the ultrasound-activated hydrogel promoted neural tissue repair and remyelination, attenuated reactive gliosis, and improved functional recovery. Collectively, this study presents a remotely activatable electroactive hydrogel for SCI repair and provides a promising strategy for dynamic bioelectrical regulation during SCI repair.