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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. 

Polymeric biomaterials exhibit excellent physicochemical characteristics as a scaffold for cell and tissue engineering applications. Chemical modification of the polymers has been the primary mode of functionalization to enhance biocompatibility and regulate cellular behaviors such as cell adhesion, proliferation, differentiation, and maturation. Due to the complexity of the in vivo cellular microenvironments, however, chemical functionalization alone is usually insufficient to develop functionally mature cells/tissues. Therefore, the multifunctional polymeric scaffolds that enable electrical, mechanical, and/or magnetic stimulation to the cells, have gained research interest in the past decade. Such multifunctional scaffolds are often combined with exogenous stimuli to further enhance the tissue and cell behaviors by dynamically controlling the microenvironments of the cells. Significantly improved cell proliferation and differentiation, as well as tissue functionalities, are frequently observed by applying extrinsic physical stimuli on functional polymeric scaffold systems. In this regard, the present paper discusses the current state-of-the-art functionalized polymeric scaffolds, with an emphasis on electrospun fibers, that modulate the physical cell niche to direct cellular behaviors and subsequent functional tissue development. We will also highlight the incorporation of the extrinsic stimuli to augment or activate the functionalized polymeric scaffold system to dynamically stimulate the cells.