Synergistic effect of endocellular calcium ion release and nanotopograpy of one-dimensional hydroxyapatite nanomaterials for accelerating neural stem cell differentiation

Neural stem cells (NSCs) based nerve repair is the most promising approach for neurodegenerative disease therapy. However, the long-time requirement for NSCs differentiation into mature neurons challenges the clinical applications of NSCs because of the missing of the best opportunity for nerve repair. In this work, we synthesized four kinds of one-dimensional (1D) hydroxyapatite (HAp) nanomaterials with different morphologies of short nanorod, long nanorod, short nanowire, and long nanowire. And we found that rapid differentiation of NSCs could be realized just by the endocytosis of 1D HAp nanomaterials with different lengths. Both the endocellular calcium ion (Ca2+) release of HAp nanosturctures suffered a low pH in endosomes and their nanotopography can regulate the neural differentiation of NSCs, and their synergistic effect is the main reason for the acceleration of NSCs differentiation. The safe, rapid and low-cost approach for promoting NSCs differentiation supposed in this work will have great potential in clinical applications for therapy of neurodegenerative diseases.