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The in vitro investigations of the crossing and diffusion of drugs through the blood\u2013brain barrier (BBB) are still not completely reliable, due to technological limits in the replication of 3D microstructures that can faithfully mimic the in vivo scenario. Here, an innovative 1:1 scale 3D\u2010printed realistic biohybrid model of the brain tumor microenvironment, with both luminal and parenchyma compartments, is presented. The dynamically controllable microfluidic device, fabricated through two\u2010photon lithography, enables the triple co\u2010culture of hCMEC\/D3 cells, forming the internal biohybrid endothelium of the capillaries, of astrocytes, and of magnetically\u2010driven spheroids of U87 glioblastoma cells. Tumor spheroids are obtained from culturing glioblastoma cells inside 3D microcages loaded with superparamagnetic iron oxide nanoparticles (SPIONs). The system proves to be capable in hindering dextran diffusion through the bioinspired BBB, while allowing chemotherapy\u2010loaded nanocarriers to cross it. The proper formation of the selective barrier and the good performance of the anti\u2010tumor treatment demonstrate that the proposed device can be successfully exploited as a realistic in vitro model for high\u2010throughput drug screening in CNS diseases.<\/jats:p>","DOI":"10.1002\/admt.202000540","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T03:56:01Z","timestamp":1598241361000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["A 3D Biohybrid Real\u2010Scale Model of the Brain Cancer Microenvironment for Advanced In Vitro Testing"],"prefix":"10.1002","volume":"5","author":[{"given":"Omar","family":"Tricinci","sequence":"first","affiliation":[{"name":"Smart Bio\u2010Interfaces Istituto Italiano di Tecnologia  Viale Rinaldo Piaggio 34 Pontedera 56025 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"De Pasquale","sequence":"additional","affiliation":[{"name":"Smart Bio\u2010Interfaces Istituto Italiano di Tecnologia  Viale Rinaldo Piaggio 34 Pontedera 56025 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attilio","family":"Marino","sequence":"additional","affiliation":[{"name":"Smart Bio\u2010Interfaces Istituto Italiano di Tecnologia  Viale Rinaldo Piaggio 34 Pontedera 56025 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Battaglini","sequence":"additional","affiliation":[{"name":"Smart Bio\u2010Interfaces Istituto Italiano di Tecnologia  Viale Rinaldo Piaggio 34 Pontedera 56025 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Pucci","sequence":"additional","affiliation":[{"name":"Smart Bio\u2010Interfaces Istituto Italiano di Tecnologia  Viale Rinaldo Piaggio 34 Pontedera 56025 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1192-3647","authenticated-orcid":false,"given":"Gianni","family":"Ciofani","sequence":"additional","affiliation":[{"name":"Smart Bio\u2010Interfaces Istituto Italiano di Tecnologia  Viale Rinaldo Piaggio 34 Pontedera 56025 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,23]]},"reference":[{"key":"e_1_2_7_1_1","volume-title":"Neurological Disorders: Public Health Challenges","author":"World Health Organization","year":"2006"},{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1016\/B978-1-4160-3966-2.00051-5","volume-title":"Modern Surgical Pathology","author":"Johnson M. 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