1 Department of Mechanical Engineering, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
2 Ottawa-Carleton Institute for Biomedical Engineering (OCIBME), Ottawa, ON, K1N 6N5, Canada.
3 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
4 Department of Chemistry and Biochemistry and the Centre for NanoScience Research, Concordia University, Montreal, QC, H4B 1R6, Canada.
5 Quebec Centre for Advanced Materials, Department of Chemistry and Biochemistry, Concordia University, Montreal, QC, H4B 1R6, Canada.
6 The Ottawa Hospital Research Institute, Ottawa, ON, K1Y 4E9, Canada.

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.