Magnetic field-oriented conductive decellularized extracellular matrix hydrogel synergizes with electrical stimulation to promote spinal cord injury repair and electrophysiological function restoration

Spinal cord injury (SCI) results in electrophysiological and behavioral dysfunction. Electrical stimulation (ES) is considered to be an effective treatment for mild SCI; however, ES is not applicable to severe SCI due to the disruption of electrical conduction caused by tissue defects. Therefore, the use of conductive materials to fill the defects and restore electrical conduction in the spinal cord is a promising therapeutic strategy. In this study, we used ultrasound to composite conductive reduced graphene oxide (rGO) and magnetic Fe₃O₄ nanoparticles and encapsulated them into gelatin methacryloyl (GelMA) along with decellularized extracellular matrix (dECM) to form a conductive composite hydrogel, rGO/Fe₃O₄/dECM@GelMA. The rGO/Fe₃O₄ complexes were able to orientate themselves in the hydrogel with a magnetic field, conferring an orientated electrical conduction function to the hydrogel. The implantation of this composite hydrogel re-established the electrical conduction in the damaged spinal cord and synergized with ES to promote the regeneration of neurons and myelinated axons at the injury site, resulting in the restoration of electrophysiological function of the spinal cord and motor function of the hind limbs of mice. Our study combines a conductive tissue-engineered scaffold with ES therapy to improve the efficacy of ES in severe spinal cord injuries and promote the restoration of spinal cord function.