Multifunctional conductive biomimetic scaffolds combined with electrical stimulation promote neural regeneration and functional recovery after spinal cord injury

Abstract Electrical stimulation (ES) is an established therapeutic strategy for nerve injury that regulates neural cell behavior and promotes tissue regeneration. Furthermore, the bio-scaffolds that are sensitive to external stimuli not only influence cell behavior through their inherent properties, but also act as a medium to receive external signals and regulate cell activity. Therefore, using scaffold materials with good electroactivity combined with exogenous ES is a potentially beneficial approach for repairing spinal cord injuries (SCI). In this research, we developed a multifunctional conductive biomimetic scaffold suitable for combined electrical stimulation therapy. Firstly, a biomimetic scaffold material (GelMA) was prepared by combining patterned nanofiber with hydrogel. Then, the stromal cell-derived factor 1 labeled with 3,4-dihydroxyphenylalanine (DOPA) (SDF-1), donepezil (DPL) and two-dimensional titanium carbide-magnesium oxide composite material (MXene-MgO) were loaded onto the surface of the scaffold. MXene-MgO, DOPA modified SDF-1 and DPL endow the scaffold material with excellent electrical conductivity, anti-inflammatory and antibacterial properties, long-term stem cell recruitment function, and the ability to prevent glial scar formation during spinal cord tissue regeneration. Cell and animal experiments showed that under ES, the MXene-MgO/SDF-1/DPL scaffold can effectively enhance the activity of neural stem cells (NSCs), promote the recovery of motor function in rats, and increase the regeneration rate of new neurons. We suggest that this multi-functional bionic scaffold can provide a new treatment strategy for spinal cord injuries, and at the same time expand the application scope of auxiliary therapies such as ES.