Formation of 3D Self-Organized Neuron-Glial Interface Derived from Neural Stem Cells via Mechano-Electrical Stimulation

Due to dissimilarities in genetics and metabolism, current animal models cannot accurately depict human neurological diseases. To develop patient-specific in vitro neural models, a functional material-based technology that offers multi-potent stimuli for enhanced neural tissue development is devised. An electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) nanofibrous scaffold is systematically optimized to maximize its piezoelectric properties while accommodating the cellular behaviors of neural stem cells. Hydro-acoustic actuation is elegantly utilized to remotely activate the piezoelectric effect of P(VDF-TrFE) scaffolds in a physiologically-safe manner for the generation of cell-relevant electric potentials. This mechano-electrical stimulation, which arose from the deflection of the scaffold and its consequent generation of electric charges on the scaffold surface under hydro-acoustic actuation, induces the multi-phenotypic differentiation of neural stem cells simultaneously toward neuronal, oligodendrocytic, and astrocytic phenotypes. As compared to the traditional biochemically-mediated differentiation, the 3D neuron-glial interface induced by the mechano-electrical stimulation results in enhanced interactions among cellular components, leading to superior neural connectivity and functionality. These results demonstrate the potential of piezoelectric material-based technology for developing functional neural tissues in vitro via effective neural stem cell modulation with multi-faceted regenerative stimuli.

Automated summary

The study introduces a functional material-based technology to develop patient-specific in vitro neural models, utilizing hydro-acoustic actuation to remotely activate the piezoelectric effect of P(VDF-TrFE) scaffolds for multi-phenotypic differentiation of neural stem cells. The mechano-electrical stimulation induced by the deflection of the scaffold leads to enhanced interactions among cellular components, resulting in improved neural connectivity and functionality in the 3D neuron-glial interface.