Alginate self-adhesive hydrogel combined with dental pulp stem cells and FGF21 repairs hemisection spinal cord injury via apoptosis and autophagy mechanisms

• A calcium alginate hydrogel combined with DPSC and FGF21 were synthesized. • Ca2+@Alg-FGF21 + DPSC promotes the reconnection of the spinal cord cross-section. • Ca2+@Alg-FGF21 + DPSC promotes cell migration and DPSC differentiation. • The hydrogel protects neurons via inhibiting apoptosis and promoting autophagy. • The hydrogel effectively promotes the recovery of motor function in HSCI mice. Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia after injury. Hemisection spinal cord injury (HSCI) is a special type of SCI. The most important difference between HSCI and SCI is the occurrence of spinal cord dissection. Therefore, a calcium alginate hydrogel combined with dental pulp stem cells (DPSCs) and fibroblast growth factor 21 (FGF21) was designed based on the principle that cadherin expression is regulated by calcium ion concentration. Each element in Ca 2+ @Alg-FGF21 + DPSC hydrogel can exert different effects 1). calcium ions can regulate cadherin to achieve self-adhesion; 2). alginic acid can absorb calcium ions to prevent calcium overload induced injury; 3) FGF21 can regulate microenvironment; 4). DPSCs can supplement exogenous neurons. The multi-factorially comprehensive effects were hypothesized to improve the HSCI recovery. It was revealed in our study that Ca 2+ @Alg-FGF21 + DPSC hydrogel could effectively promote the recovery after spinal cord hemisection in mice via regulating apoptosis and autophagy, providing potential clues and cues of using Ca2+@Alg-FGF21 + DPSC hydrogel for HSCI treatment.