Wireless Electrical Stimulation via a Conductive Hydrogel Scaffold Synergizes With Stem Cell Transplantation Therapy to Promote Traumatic Brain Injury Repair

Electrical stimulation (ES) offers a robust approach to boost the efficacy of stem cell transplantation therapy for the treatment of neurological disorders. Notably, wireless technology blends convenience with the elimination of infection risk posed by wired connections, but the challenge lies in the integration of wireless-enabled stimulation materials and stem cell carriers. Here, we describe a flexible annular conductive dopamine-modified hyaluronic acid (HAD)/polyvinyl alcohol (PVA)/carbon nanotube‌ (CNT) hydrogel that acts as a secondary coil to realize wireless ES via electromagnetic induction, while also serving as a three-dimensional (3D) scaffold carrier for endogenous neural stem cells (NSCs). Established on the annular HAD/PVA/CNT hydrogel with high conductivity and good biocompatibility, wireless ES significantly enhances neuronal differentiation of NSCs. Furthermore, transplantation of the NSC-laden annular hydrogel into a traumatic brain injury (TBI) rat model modulates the behaviors of both exogenous and endogenous neural cells. The combined therapy of wireless ES and NSC transplantation promotes neuronal differentiation in both the injury zone and hippocampus in association with the PI3K-Akt pathway, reduces post-traumatic inflammatory responses, and effectively restores motor and memory functions in TBI rats. This study offers a promising therapeutic strategy of integrating wireless ES with stem cell transplantation therapy for brain injury repair.