Electricity is important in the physiology and development of human tissues such as embryonic and fetal development, and tissue regeneration for wound healing. Accordingly, electrical stimulation (ES) is increasingly being applied to influence cell behavior and function for a biomimetic approach to in vitro cell culture and tissue engineering. Here, the application of conductive polymer (CP) poly(3,4‐ethylenedioxythiophene)‐polystyrenesulfonate (PEDOT:PSS) pillars is described, direct‐write printed in an array format, for 3D ES of maturing neural tissues that are derived from human neural stem cells (NSCs). NSCs are initially encapsulated within a conductive polysaccharide‐based biogel interfaced with the CP pillar microelectrode arrays (MEAs), followed by differentiation in situ to neurons and supporting neuroglia during stimulation. Electrochemical properties of the pillar electrodes and the biogel support their electrical performance. Remarkably, stimulated constructs are characterized by widespread tracts of high‐density mature neurons and enhanced maturation of functional neural networks. Formation of tissues using the 3D MEAs substantiates the platform for advanced clinically relevant neural tissue induction, with the system likely amendable to diverse cell types to create other neural and non‐neural tissues. The platform may be useful for both research and translation, including modeling tissue development, function and dysfunction, electroceuticals, drug screening, and regenerative medicine.

Direct writing is an effective and versatile technique for three-dimensional (3D) fabrication of conducting polymer (CP) structures. It is precisely localized and highly controllable, thus providing great opportunities for incorporating CPs into microelectronic array devices. Herein we demonstrate 3D writing and characterization of poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS) pillars in an array format, by using an in-house-constructed variant of scanning ion conductance microscopy (SICM). CP pillars with different aspect ratios were successfully fabricated by optimizing the writing parameters: pulling speed, pulling time, concentration of the polymer solution, and the micropipette tip diameter. Especially, super high aspect ratio pillars of around 7 μm in diameter and 5000 μm in height were fabricated, indicating a good capability of this direct writing technique. Additions of an organic solvent and a cross-linking agent contribute to a significantly enhanced water stability of the pillars, critical if the arrays were to be used in biologically relevant applications. Surface morphologies and structural analysis of CP pillars were characterized by scanning electron microscopy and Raman spectroscopy, respectively. Electrochemical properties of the individual pillars of different heights were examined by cyclic voltammetry using a double-barrel micropipette as an electrochemical cell. Exceptional mechanical properties of the pillars, such as high flexibility and robustness, were observed when bent by applying a force. The 3D pillar arrays are expected to provide versatile substrates for functionalized and integrated biological sensing and electrically addressable array devices.

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