Abstract
Neuronal disorders are characterized by the loss of functional neurons and disrupted neuroanatomical connectivity, severely impacting the quality of life of patients. This study investigates a novel electroconductive nanocomposite consisting of glycine-derived carbon nanodots (GlyCNDs) incorporated into a collagen matrix and validates its beneficial physicochemical and electro-active cueing to relevant cells. To this end, this work employs mouse induced pluripotent stem cell (iPSC)-derived neural progenitor (NP) spheroids. The findings reveal that the nanocomposite markedly augmented neuronal differentiation in NP spheroids and stimulate neuritogenesis. In addition, this work demonstrates that the biomaterial-driven enhancements of the cellular response ultimately contribute to the development of highly integrated and functional neural networks. Lastly, acute dizocilpine (MK-801) treatment provides new evidence for a direct interaction between collagen-bound GlyCNDs and postsynaptic N-methyl-D-aspartate (NMDA) receptors, thereby suggesting a potential mechanism underlying the observed cellular events. In summary, the findings establish a foundation for the development of a new nanocomposite resulting from the integration of carbon nanomaterials within a clinically approved hydrogel, toward an effective biomaterial-based strategy for addressing neuronal disorders by restoring damaged/lost neurons and supporting the reestablishment of neuroanatomical connectivity.