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While existing polydimethylsiloxane (PDMS)\u2010based microfluidic platforms offer precise architectures, the cultured neurons grow on two\u2010dimensional (2D) planar multielectrode arrays (MEA). To mimic the native microenvironment, where neurons grow in three\u2010dimensional (3D) extracellular matrices (ECM), 3D hydrogels can be designed to encapsulate cells and enable physiologically mimicked behaviors. Here, we describe \u2018hydroMEA,\u2019 a 3D platform fabricated by placing PDMS microstructures on a high\u2010density MEA and filled with a desired hydrogel, to offer controlled topologies, physiologically relevant microenvironments, and real\u2010time electrophysiological measurements. First, we developed a gelatin methacryloyl (GelMA) hydrogel with incorporated ECM components and tuned the mechanical properties to match those of nerve tissue. The hydrogel was able to support: (1) the growth of iPSC\u2010derived sensory neurons (hSNs) for &gt;100 days; (2) co\u2010cultures of hSN with human embryonic stem cell\u2010derived Schwann cells (hSCs), to enable reliable 3D myelination. Next, hydroMEA were prepared for topologically defined 3D growth and myelination in designated compartments. Finally, electrophysiological evaluation of hSN\u2010hSCs co\u2010cultures revealed increased conduction speeds indicating functional myelin. This platform is a promising tool to study cell\u2010cell interactions and to functionally evaluate the effect of pharmacological compounds in a more translational manner.<\/jats:p>","DOI":"10.1002\/adhm.71655","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:24:21Z","timestamp":1787804661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HydroMEA: A 3D Hydrogel\u2010Based Microfluidic Device to Study Electrophysiology for Myelinated Nerve\u2010on\u2010Chip"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-0469","authenticated-orcid":false,"given":"Blandine F.","family":"Cl\u00e9ment","sequence":"first","affiliation":[{"name":"Laboratory of Biosensors and Bioelectronics Institute for Biomedical Engineering  Z\u00fcrich 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