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Abstract Electrospinning is a versatile method for synthesizing nanofibrous structures from nearly all polymers, offering a solution for the industrial‐scale mass production of nanomaterials in a wide range of applications. However, the continuous non‐woven structure intrinsic to electrospun fibers limits their applications, where a smaller length scale is desired. Here, we present a novel method to synthesize polymeric nanofiber‐fragments based on colloid electrospinning of polymer and sacrificial silica nanoparticles, followed by mechanical fracturing with ultrasonication. The size and hydrophobicity of silica nanoparticles are optimized for their improved integration within the polymer matrix, and the controllability of nanofiber‐fragment length by the amount of silica nanoparticle loading, down to 2 µm in length for poly(vinylidene fluoride‐trifluoroethylene) nanofibers with an average fiber diameter of approximately 100 nm, is shown. The resultant nanofiber‐fragments are shown to maintain their material properties including piezoelectric coefficients and their enhanced injectability for drug delivery application is demonstrated with an animal model. 

Abstract 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.