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However, mature neurons are delicate and susceptible to manipulation. Here, extrusion\u2010based 3D bioprinting is employed to fabricate gelatin methacryloyl (GelMA)\u2010based constructs containing embryonic day 18 (E18) rat cortical neurons, referred to as 3D neuMatrix. 3D neuMatrix displays favorable neuronal viability, with the progressive formation of a 3D brain\u2010like neural network with local and long\u2010range functional axon connections. Compared with 2D cultured neurons, 3D neuMatrix is more similar to the E18 cortex according to the bulk transcriptomic profile, with a recreation of cellular components in the cerebral cortex. The 3D neuMatrix is employed to establish a disease model of ischemic stroke, with a faithful recapitulation of the viability, function, and transcriptomic features of rats with middle cerebral artery occlusion\/reperfusion (MCAO\/R). These findings demonstrate the formation of multiscale neural circuits within 3D neuMatrix and its valuable potential in the study of neurodevelopment, disease modeling with drug screening, and in vitro intelligence.<\/jats:p>","DOI":"10.1002\/advs.202504455","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T08:15:33Z","timestamp":1748420133000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix"],"prefix":"10.1002","volume":"12","author":[{"given":"Huiyu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery PUMCH PUMC &amp; CAMS  Beijing 100730 China"},{"name":"Eight\u2010Year Medical Doctor Program CAMS &amp; PUMC  Beijing 100730 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