Engineering neuroregenerative microenvironment via aligned hydrogel-assisted magnetic stimulation for complete spinal cord injury repair

Utilizing biomaterials in tissue engineering has shown considerable promise for tissue regeneration, particularly through delivering multimodel cell-regulatory signals, including the material-related signals and extrinsic stimuli. In this research, we developed a magnetic-responsive aligned nanofiber fibrin hydrogel (MAFG), integrating the structured alignment of nanofibers and the pliability of fibrin hydrogel with an external magnetic field. This design aimed to enhance the regenerative response in spinal cord injury treatment. A medium-strength magnetic field, aligned with the spinal cord, was applied to aid motor function recovery in rats with spinal cord injuries. The use of MAFG in this context not only intensified the effect of the magnetic field but also encouraged the activation and differentiation of native neural stem cells. Furthermore, this method effectively steered macrophage polarization towards a beneficial M2 phenotype, addressing immune dysregulation at the injury site. The parallel application of magnetic field stimulation through MAFG in a spinal cord injury model contributed to the concurrent promotion of neurogenesis, angiogenesis, and immunomodulation, resulting in marked improvement in motor function in rats. This investigation underscores the therapeutic potential of magnetic field stimulation and highlights how aligning this stimulation with the spinal cord can significantly enhance the regenerative milieu at the injury site.