Multifunctional magneto-electric and exosome-loaded hydrogel enhances neuronal differentiation and immunoregulation through remote non-invasive electrical stimulation for neurological recovery after spinal cord injury

Intervention in the differentiation of neural stem cells (NSCs) is emerging as a highly promising approach for the treatment of spinal cord injury (SCI). However, NSCs at the injury site often suffer from low survival and uncontrolled differentiation. Whereas electrical stimulation has proven effective in regulating the fate of NSCs and promoting tissue repair, however, conventional electrical stimulation therapy has failed to be widely applied due to challenges such as invasiveness and technical complexity. To overcome these limitations, we developed a biomimetic magneto-electric hydrogel incorporating Fe₃O₄@BaTiO₃ core-shell nanoparticles and human umbilical mesenchymal stem cell exosomes (HUMSC-Exos) around the concept of constructing remote noninvasive electrical stimulation for the synergistic treatment of SCI. The Fe₃O₄@BaTiO₃ is activated by the peripheral magnetic field to generate electrical stimulation, which, in conjunction with the synergistic effects of HUMSC-Exos, significantly alleviates the early inflammatory response associated with SCI and enhances the regeneration of newborn neurons and axons, thereby creating favorable conditions for functional recovery post-SCI. Our findings indicate that applying this magneto-exosome hydrogel in a rat model of SCI leads to substantial functional recovery. This innovative combination represents a promising therapeutic strategy for SCI repair.