{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:35:30Z","timestamp":1792802130760,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>This study presents the development of a Nervous System-on-Chip (NoC) using microfabrication techniques, focusing on the integration of human induced pluripotent stem cell (hiPSC)-derived neurons. We designed and fabricated NoCs based on microtunnel devices (MDs) with radial and linear configurations to facilitate the compartmentalized culture of cortical and enteric neural networks. Our findings demonstrate that these MDs allow axonal growth while restricting migration of somas and dendrites between compartments, thereby promoting the formation of organized neural networks. This creates a microfluidic platform capable of supporting the growth of different culture systems, which could potentially be combined to study interactions between the central and enteric nervous systems. The resulting neuronal networks exhibited viability, expression of key lineage markers, and synapse formation, highlighting the platform\u2019s potential for advanced nervous system modeling. MD-based NoC models provide an innovative microfluidic platform for studying the biology of human neural networks, with implications for the investigation of neurodegenerative diseases such as Parkinson\u2019s Disease and applications in pre-clinical research.<\/jats:p>","DOI":"10.3390\/mi17020199","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:00:47Z","timestamp":1770033647000},"page":"199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nervous System-on-Chip: Innovative Microfluidic Platform to Compartmentalize hiPSC-Derived Neural Networks"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3534-7218","authenticated-orcid":false,"given":"Rahman","family":"Sabahi-Kaviani","sequence":"first","affiliation":[{"name":"Neuro-Nanoscale Engineering, Department of Mechanical Engineering\/Microsystems and Institute of Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-2426","authenticated-orcid":false,"given":"Antigoni","family":"Gogolou","sequence":"additional","affiliation":[{"name":"Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK"},{"name":"Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Souilhol","sequence":"additional","affiliation":[{"name":"Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK"},{"name":"Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5517-3687","authenticated-orcid":false,"given":"Mark","family":"van der Kroeg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9777-3338","authenticated-orcid":false,"given":"Steven A.","family":"Kushner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0825-3806","authenticated-orcid":false,"given":"Femke M. S.","family":"de Vrij","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2184-2990","authenticated-orcid":false,"given":"Anestis","family":"Tsakiridis","sequence":"additional","affiliation":[{"name":"Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK"},{"name":"Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8486-5866","authenticated-orcid":false,"given":"Regina","family":"Luttge","sequence":"additional","affiliation":[{"name":"Neuro-Nanoscale Engineering, Department of Mechanical Engineering\/Microsystems and Institute of Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands"},{"name":"Eindhoven Artificial Intelligence Systems Institute and Casimir Institute, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/s41551-024-01236-0","article-title":"Standardizing Designed and Emergent Quantitative Features in Microphysiological Systems","volume":"8","author":"Nahon","year":"2024","journal-title":"Nat. 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