Combination therapy of fingolimod-GelMA hydrogel loaded with neural stem cells and electrical stimulation promotes recovery of spinal cord injury

Spinal cord injury (SCI) is one of the most devastating diseases worldwide, and its recovery is hindered by damage and loss of nerve endings leading to loss of neurons and formation of glial scars. In this study, an injectable GelMA hydrogel incorporating neural stem cells (NSCs) and fingolimod (FTY720), combined with electrical stimulation (ES), was developed to enhance neural regeneration and suppress glial scar formation in a rat SCI model of complete spinal cord transection. The combined therapy of ES and injectable hydrogel incorporated with FTY720 improved both proliferation and neuronal differentiation and inhibited astrocytic differentiation of NSCs <i>in vitro</i>. When applied to a complete transected SCI rat model, the combined therapy significantly enhanced neuronal regeneration and reduced glial scar formation in the lesioned area, thus resulting in better motor function recovery. Taken together, this research demonstrated a promising FTY720 enhanced GelMA hydrogel loaded with NSCs for exogenous NSCs delivery and provided a novel strategy for combination therapy of SCI. In this study, an injectable hydrogel loaded with NSCs and FTY720 was successfully prepared. Combined therapy of FTY720 enhanced GelMA hydrogel loaded with NSCs and electrical stimulation enhance SCI recovery. Combined therapy of NSCs-loaded FTY720-GelMA and ES promoted neuronal regeneration and reduced glial scar formation after SCI.