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In this study, nanopatterned Nafion microelectrode arrays for in vitro cardiac electrophysiology are reported. With the aim of defining sophisticated Nafion nanostructures with highly ionic conductivity, fabrication parameters such as Nafion concentration and curing temperature are optimized. By increasing curing temperature and Nafion concentration, the replication fidelity of Nafion nanopatterns when copied from a polydimethylsiloxane master mold are controlled. It is also found that cross‐sectional morphology and ion current density of nanopatterned Nafion strongly depends on the fabrication parameters. To investigate this dependency, current‐voltage analysis is conducted using organic electrochemical transistors overlaid with patterned Nafion substrates. Nanopatterned Nafion is found to allow higher ion current densities than unpatterned surfaces. Furthermore, higher curing temperatures are found to render Nafion layers with higher ion/electrical transfer properties. To optimize nanopattern dimensions, electrical current flows, and film uniformity, a final configuration consisting of 5% nanopatterned Nafion cured at 65 °C is chosen. Microelectrode arrays (MEAs) are then covered with optimized Nafion nanopatterns and used for electrophysiological analysis of two types of induced pluripotent stem cell‐derived cardiomyocytes (iPSCs‐CMs). These data highlight the suitability of nanopatterned Nafion, combined with MEAs, for enhancing the cellular environment of iPSC‐CMs for use in electrophysiological analysis in vitro.

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Tissue engineering with human induced pluripotent stem cell-derived cardiomyocytes enables unique opportunities for creating physiological models of the heart in vitro. However, there are few approaches available that can recapitulate the complex structure-function relationships that govern cardiac function at the macroscopic organ level. Here, we report a down-scaled, conical human 3D ventricular model with controllable cellular organization using multilayered, patterned cardiac sheets. Tissue engineered ventricles whose cardiomyocytes were pre-aligned parallel or perpendicular to the long axis outperformed those whose cardiomyocytes were angled or randomly oriented. Notably, the inner layers of perpendicular cardiac sheets realigned over 4 days into a parallel orientation, creating a helical transmural architecture, whereas minimal remodeling occurred in the parallel or angled sheets. Finite element analysis of engineered ventricles demonstrated that circumferential alignment leads to maximal perpendicular shear stress at the inner layer, whereas longitudinal orientation leads to maximal parallel stress. We hypothesize that cellular remodeling occurs to reduce perpendicular shear stresses in myocardium. This advanced platform provides evidence that physical forces such as shear stress drive self-organization of cardiac architecture.

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