Graphene Nano-Fiber Composites for Enhanced Neuronal Differentiation of Human Mesenchymal Stem Cells†
Abstract Graphene-based nanocomposites have been extensively employed to design biomimetic platforms epitomizing the structural and functional complexity of the tissue with increased robustness and physiological relevance. The adhesive and mechanical cues provided by such nanocomposite microenvironment kindles the cell fate decisions. Owing to their differentiation and regenerative potential, Human Mesenchymal Stem Cells (hMSCs) have proven to be a promising candidate for treating several neurodegenerative disorders. However, their degree of differentiation and its reproducibility is often jeopardized by multiple levels of heterogeneity, thereby compromising their translational utilization. Baffled at this crossroad, we designed a one-step approach to electrospin Poly-caprolactone (PCL) nanocomposite, with varying graphene concentrations, to capture, for the first time, the realms of their biocompatible and anisotropic characteristics, providing biomimetic platforms for improved differentiation of human bone marrow-derived MSCs (hMSCs) into neurons. Interestingly, PCL having 0.05% graphene (PCL-G0.05) showcased an ideal nano-topography with an unprecedented combination of guidance stimuli and substrates cues, aiding in enhanced differentiation of hMSCs into dopaminergic neurons (DA). These newly differentiated DA neurons were characterized at gene, protein, and functional levels and were seen to exhibit unique neuronal arborization, enhanced intracellular Ca2+ influx, and dopamine secretion, thereby opening new horizons for pre-clinical and clinical applications.