{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:02:06Z","timestamp":1792785726896,"version":"4.5.0"},"reference-count":38,"publisher":"IOP Publishing","issue":"4","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"}],"funder":[{"name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","award":["MI 1_02824450999_0000622"],"award-info":[{"award-number":["MI 1_02824450999_0000622"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biofabrication"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The quantitative investigation of functional connectivity across spatially organized neuronal networks remains a major challenge in human three-dimensional (3D)\n                    <jats:italic>in vitro<\/jats:italic>\n                    models. Although neurospheroids, brain organoids, and microfluidic systems enable controlled structural organization and guided neurite growth, their integration with high-resolution electrophysiological interfaces remains limited, often requiring post hoc adaptations that compromise recording stability and long-term reproducibility. Here, we present a polydimethylsiloxane (PDMS) microfluidic platform natively engineered for seamless integration with high-density microelectrode arrays (HD-MEAs), enabling the controlled interconnection and long-term electrophysiological interrogation of human neurospheroids within a defined geometry. The platform supports reproducible axonal growth between spatially separated spheroids while preserving full compatibility with HD- microelectrode arrays (MEA) recording requirements and electrical stability. Structural characterization revealed the formation of a stable inter-spheroid axonal fascicle enriched in neuronal and synapse-associated markers, supported by ultrastructural analyzes across multiple spatial scales. Long-term electrophysiological recordings revealed progressive electrophysiological maturation-associated changes, characterized by increased mean firing rate, sustained and spatially confined neuronal activity within each spheroid, and changes in burst dynamics. Quantitative cross-correlation analysis identified lag-consistent interaction patterns compatible with both local (intra-spheroid) and long-range (inter-spheroid) putative functional connectivity, enabling the distinction between local and distributed network dynamics within the modular system. By combining controlled 3D architecture, stable HD-MEA integration, and quantitative electrophysiological readouts, this platform establishes a robust, reproducible and human-relevant framework for investigating activity patterns compatible with functional connectivity dynamics in interconnected neuronal assemblies, with potential applications in disease modeling and connectopathies-related studies.\n                  <\/jats:p>","DOI":"10.1088\/1758-5090\/aea7de","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:53:11Z","timestamp":1789512791000},"page":"045005","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A high-density microelectrode array integrated microfluidic platform for quantitative investigation of functional connectivity in interconnected human dopaminergic neurospheroids"],"prefix":"10.1088","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3756-6740","authenticated-orcid":false,"given":"Chiara","family":"Ausilio","sequence":"first","affiliation":[{"name":"Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia (IIT)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2354-8509","authenticated-orcid":true,"given":"Annachiara","family":"Scalzone","sequence":"additional","affiliation":[{"name":"Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia (IIT)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Mollo","sequence":"additional","affiliation":[{"name":"Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia (IIT)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2435-7181","authenticated-orcid":true,"given":"Paolo Antonio","family":"Netti","sequence":"additional","affiliation":[{"name":"Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia (IIT)"},{"name":"Dipartimento di Chimica Materiali e Produzione Industriale Universit\u00e0 di Napoli Federico II"},{"name":"Interdisciplinary Research Centre on Biomaterials (CRIB), Universit\u00e0 di Napoli Federico II"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"bfaea7debib1","doi-asserted-by":"publisher","first-page":"5142","DOI":"10.1038\/s41467-024-48905-x","type":"journal-article","article-title":"Bi\u0153muS: a new tool for neurological disorders studies through real-time emulation and hybridization using biomimetic spiking neural network","volume":"15","author":"Beaubois","year":"2024","journal-title":"Nat. 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Published by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2026-06-11","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-09-15","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-09-28","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}