Black phosphorus nanosheets promote neuronal differentiation of neural stem cells through adhesion and pinocytosis for spinal cord injury repair

Spinal cord injury (SCI) is a severe neurological and pathological disorder, but there are few effective treatments that can significantly promote functional recovery after SCI. Neural stem cell (NSC) transplantation therapy is considered a promising approach to repair neural connection and enhance functional recovery. However, a series of pathological changes at the injury site make the microenvironment unfavorable for NSC neuronal differentiation. In this study, black phosphorus nanosheets (BPNSs), a kind of nanomaterial which degraded into phosphate anions, exhibited good biocompatibility and effective function on regulating NSC differentiation. In vitro, BPNSs can promote neuronal differentiation of NSC by upregulating the p53 signaling pathway via activating membrane receptors and intracellular receptors mediated by its adhesin and cell pinocytosis. In vivo, BPNSs-treated NSCs transplantation could promote neural regeneration and functional recovery effectively. In conclusion, our results suggest that BPNSs have the potential to be a nanomedical strategy for the repair of SCI. STATEMENT OF SIGNIFICANCE: Black phosphorus nanosheets (BPNSs), which are composed of the single chemical element phosphorus that is a fundamental component of biological systems, exhibit good biocompatibility, as they predominantly degrade into phosphate anions. BPNSs are quickly internalized by neural stem cells (NSCs) within 6 h and can promote NSC neuronal differentiation by upregulating the p53 signaling pathway. Transplantation of NSCs pre-treated with BPNSs effectively promotes nerve regeneration and facilitates significant functional recovery following spinal cord injury.