{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:15:10Z","timestamp":1785413710209,"version":"3.56.0"},"reference-count":94,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"Chinese Scholarship Council","doi-asserted-by":"publisher","award":["202106170022"],"award-info":[{"award-number":["202106170022"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"award":["202106170022"],"award-info":[{"award-number":["202106170022"]}],"id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Health-Holland Top consortium for Knowledge and Innovation in Life Sciences & Health (TKI-LSH) grant BEACON","award":["EMCLSH24052"],"award-info":[{"award-number":["EMCLSH24052"]}]},{"name":"European Union\u2019s Horizon Europe research and innovation program grant NEOLIVER bioprinting","award":["101191649"],"award-info":[{"award-number":["101191649"]}]},{"name":"Convergence Health Technology Flagship grant \u201cOrgan Transplantation\u201d of the Erasmus MC and TU Delft"},{"id":[{"id":"https:\/\/ror.org\/02e2c7k09","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Drug-induced liver injury (DILI) remains a major cause of acute liver failure and drug withdrawal from the market. Recently developed three-dimensional (3D) hepatic in vitro systems exhibit improved functionality and drug sensitivity compared with conventional two-dimensional cultures. These 3D models range from simple physiologic-like culture systems to advanced bioreactors with dynamic flow to provide sufficient nutrients and consistent drug exposure. However, whether dynamic perfusion improves sensitivity and reproducibility of hepatotoxicity testing remains unclear. Here, we developed a tailor-made perfusion platform to support volumetric bioprinted hepatic constructs for hepatotoxicity testing. The constructs consist of intrahepatic cholangiocyte organoids (ICOs) differentiated towards hepatocyte lineage and embedded in a gelatin methacryloyl bioresin. For toxicity evaluation, the hepatocyte-like ICO constructs were exposed to prolonged subtoxic acetaminophen treatment (10 mM, 7 days). The perfusion system effectively maintained and enhanced hepatocyte differentiation, evidenced by upregulated hepatic markers under perfused conditions compared to static controls. Testing of acetaminophen hepatotoxicity revealed that the perfused constructs displayed elevated cellular injury, with markedly higher liver injury markers relative to controls. Collectively, this study demonstrates the successful application of perfusion-based 3D model culture and highlights its potential as a more physiological platform for hepatotoxicity risk assessment in drug discovery and regenerative medicine.<\/jats:p>","DOI":"10.3390\/cells15151342","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:15:56Z","timestamp":1785140156000},"page":"1342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rapid Volumetric Bioprinting Coupled with Dynamic Perfusion Enhances Human Hepatic Organoid Toxicity Testing"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6198-7046","authenticated-orcid":false,"given":"Yu","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0875-5438","authenticated-orcid":false,"given":"Paulina","family":"N\u00fa\u00f1ez Bernal","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Gin\u00e9s Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7141-9939","authenticated-orcid":false,"given":"Manon Christel","family":"Bouwmeester","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1770-4153","authenticated-orcid":false,"given":"Tom J. G.","family":"Walraven","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"},{"name":"Division of Toxicology, Wageningen University and Research, 6708 WE Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Wanders","sequence":"additional","affiliation":[{"name":"LifeTec Group BV, 5611 ZS Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Kock","sequence":"additional","affiliation":[{"name":"LifeTec Group BV, 5611 ZS Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nura van","family":"Heck","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8109-7657","authenticated-orcid":false,"given":"Kerstin","family":"Schneeberger-Verjaal","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0651-5334","authenticated-orcid":false,"given":"Luc J. W.","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-0560","authenticated-orcid":false,"given":"Bart","family":"Spee","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1136\/gutjnl-2016-313369","article-title":"Drug-induced liver injury: Recent advances in diagnosis and risk assessment","volume":"66","author":"Andrade","year":"2017","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17562848231163410","DOI":"10.1177\/17562848231163410","article-title":"Drug-induced liver injury: A comprehensive review","volume":"16","author":"Hosack","year":"2023","journal-title":"Ther. 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