Hydroxyapatite Nanorods Function as Safe and Effective Growth Factors Regulating Neural Differentiation and Neuron Development

Abstract Neural stem cell (NSC) transplantation is one of the most promising therapeutic strategies for neurodegenerative diseases. However, the slow spontaneous differentiation of NSCs often hampers their application in neural repair. Although some biological growth factors accelerate the differentiation of NSCs, their high cost, short half‐life, and unpredictable behavior in vivo, as well as the complexity of the operation, hinder their clinical use. In this study, it is demonstrated that hydroxyapatite (HAp), the main component of bone, in the form of nanorods, can regulate the neural differentiation of NSCs and maturation of the newly differentiated cells. Culturing NSCs with HAp nanorods leads to the differentiation of NSCs into mature neurons that exhibit well‐defined electrophysiological behavior within 5 days. The state of these neurons is much better than when culturing the cells without HAp nanorods, which undergo a 2‐week differentiation process. Furthermore, RNA‐sequencing data reveal that the neuroactive ligand–receptor interaction pathway is dominant in the enriched differentiated neuronal population. Hence, inorganic growth factors like HAp act as a feasible, effective, safe, and practical tool for regulating the differentiation of NSCs and can potentially be used in the treatment of neurodegenerative diseases.