Electroconductive Collagen-Carbon Nanodots Nanocomposite Elicits Robust Neurite Outgrowth, Supports Neurogenic Differentiation and Accelerates Electrophysiological Maturation of iPSCs in Neural Progenitor Spheroids.

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, we employed mouse induced pluripotent stem cell (miPSC)-derived neural progenitor (NP) spheroids and 3D cultures of primary neurons. Our findings revealed that the nanocomposite markedly augmented neuronal differentiation in NP spheroids and stimulated neuritogenesis. In addition, we demonstrated that the biomaterial-driven enhancements of the cellular response ultimately contributed to the development of highly integrated and functional neural networks. Lastly, acute MK-801 treatment provided new evidence for a direct interaction between collagen-bound GlyCNDs and post-synaptic NMDA receptors, thereby suggesting a potential mechanism underlying the observed cellular events. In summary, our findings establish a foundation for the development of a new nanocomposite resulting from the integration of carbon nanomaterials within a clinically approved hydrogel, towards an effective biomaterial-based strategy for addressing neuronal disorders by restoring damaged/lost neurons and supporting the reestablishment of neuroanatomical connectivity. This article is protected by copyright. All rights reserved.