Piezotronic effect for in situ electrostimulation of neural stem cell therapy for nerve injury

Nerve injury threatens the health of humans and causes death and disability in adults worldwide. The difficulty of recovery from nerve injury is that there is no newborn functional tissue to fill the damaged tissue. Transplantation of neural stem cells (NSCs) is a potential therapy for nerve injury because of the ability of NSCs to differentiate into different kinds of functional cells. However, non-directed nature of differentiation and lack of functional neurons limit the application of NSCs transplantation. Electrical stimulation can promote the neuronal differentiation of NSCs, which may improve the therapeutic efficacy of NSC transplantation in brain tissue. Cellulose nanofibers (CNFs) possess good piezotronic effect and biocompatibility, which provides the possibility of wireless electric stimulation of NSC differentiation. In this study, based on piezotronic effect, natural cellulose nanofibers (CNFs) were proposed to promote the neuronal differentiation of NSCs with the ultrasound treatment. In vitro, ultrasound-driven CNF treatment promoted NSCs to differentiate into functional neurons and form a neural network that was able to transfer nerve impulses. Transplantation of NSCs combined with CNFs promoted nerve regeneration in a rat model under ultrasound treatment. The newborn nerve tissue derived from implanted NSCs effectively rebuilds neural function. In conclusion, this study demonstrates that transplantation therapy with NSCs combined with ultrasound-driven CNF treatment has potential for applications in neural regeneration.