Chiral Nanoagonist Targeting EGFR for Nerve Injury Repair

Abstract Nerve injury repair is limited by the incapacity to regenerate neurons in the nervous system. Epidermal growth factor receptor (EGFR) plays an important role in the development of the nervous system, but its potential in nerve regeneration and repair has remained underappreciated. Herein, a chiral nanoagonist, D ‐Histidine ZnO nanorods (NRs), is reported to effectively activate EGFR and initiate multiple downstream cascade signaling pathways, promoting nerve cell proliferation, differentiation, and migration in three different types of neural cells. D ‐Histidine ZnO NRs not only achieve more than 85% differentiation rate (with neurite length larger than 50 µm), but also induce the transdifferentiating of Schwann cells into a stem‐like phenotype. A biodegradable band‐aid‐like bandage incorporating D ‐Histidine ZnO NRs is developed and applied in nerve injury repair in both sciatic nerve and spinal cord injury models. The neurorestoration and functional recovery are significantly improved after 4‐week therapy. This study reveals that chirality‐dependent regulation of nerve cell behavior by chiral nanoagonist targeting EGFR is a pioneering and promising strategy in nerve regeneration therapies.