{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:04:08Z","timestamp":1783440248126,"version":"3.54.6"},"reference-count":88,"publisher":"Wiley","issue":"37","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21EB034423\u201001A1"],"award-info":[{"award-number":["1R21EB034423\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AI183529\u201001"],"award-info":[{"award-number":["1R01AI183529\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The lack of physiologically relevant in vitro models remains a limitation in liver transplantation research. Progress in organ\u2010on\u2010a\u2010chip technologies enables the generation of clinically translatable data in vitro. A vascularized liver tissueoid\u2010on\u2010a\u2010chip (LToC) model is engineered to replicate human liver tissue's structural and functional features for modeling liver regeneration and allograft rejection. The LToC comprises a microfluidic device containing donor\u2010matched human hepatic progenitor cells and intrahepatic portal vein endothelial cells embedded in a fibrin matrix and maintained in dynamic culture for 49 days. The system supports self\u2010assembly into a perfusable microvascular network and liver lobule\u2010like architecture, with &gt;95% cell viability, stable vascular integrity, and active hepatic function (albumin, urea, complement factors, and hepatocyte growth factor secretion). The mature tissueoid includes hepatocytes (CK18\n                    <jats:sup>+<\/jats:sup>\n                    , albumin\n                    <jats:sup>+<\/jats:sup>\n                    , CYP2D6\n                    <jats:sup>+<\/jats:sup>\n                    ), cholangiocytes (CK19\n                    <jats:sup>+<\/jats:sup>\n                    , EPCAM\n                    <jats:sup>+<\/jats:sup>\n                    ), Kupffer cells (CD68\n                    <jats:sup>+<\/jats:sup>\n                    ), stellate cells (PDGFR\u2010\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    ), and endothelial cells (CD31\n                    <jats:sup>+<\/jats:sup>\n                    ). Perfusion with allogeneic T cells induces cellular rejection, characterized by decreased viability, endothelial disruption, hepatic marker loss, HLA\u2010I upregulation, and a proinflammatory cytokine response (IL\u20106, TNF\u2010\u03b1, IL\u20101\u03b2, IFN\u2010\u03b3, granzyme A and B, and perforin). The LToC provides a physiologically relevant platform for studying immune\u2010mediated liver injury, tissue regeneration, and allograft rejection, with potential applications in immunosuppressive drug testing and personalized transplant medicine.\n                  <\/jats:p>","DOI":"10.1002\/adma.202521178","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T07:58:25Z","timestamp":1770623905000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liver Tissueoid on\u2010a\u2010Chip Modeling Liver Regeneration and Allograft Rejection"],"prefix":"10.1002","volume":"38","author":[{"given":"Abdul Rahim Chethikkattuveli","family":"Salih","sequence":"first","affiliation":[{"name":"Terasaki Institute for Biomedical Innovation  Woodland Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Peirsman","sequence":"additional","affiliation":[{"name":"Terasaki Institute for Biomedical Innovation  Woodland Hills California USA"},{"name":"Plastic, Reconstructive and Aesthetic Surgery Ghent University Hospital  Ghent Oost\u2010Vlaanderen Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danial","family":"Khorsandi","sequence":"additional","affiliation":[{"name":"Terasaki Institute for Biomedical Innovation  Woodland Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Ferrao","sequence":"additional","affiliation":[{"name":"Terasaki Institute for Biomedical Innovation  Woodland Hills California USA"},{"name":"Institute for Interdisciplinary Research Doctoral Programme in Experimental Biology and Biomedicine (PDBEB) University of Coimbra  Coimbra Portugal"},{"name":"CIBB \u2013 Center for Innovative Biomedicine and Biotechnology  Coimbra"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Institute for Interdisciplinary Research Doctoral Programme in Experimental Biology and Biomedicine (PDBEB) University of Coimbra  Coimbra Portugal"},{"name":"Faculty of Medicine Institute of Pharmacology and Experimental Therapeutics University of Coimbra  Coimbra Portugal"},{"name":"CIBB \u2013 Center for Innovative Biomedicine and Biotechnology  Coimbra"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Kamaraj","sequence":"additional","affiliation":[{"name":"Terasaki Institute for Biomedical Innovation  Woodland Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnson V.","family":"John","sequence":"additional","affiliation":[{"name":"Terasaki Institute for Biomedical Innovation  Woodland Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles","family":"Baquerizo","sequence":"additional","affiliation":[{"name":"Terasaki Institute for Biomedical Innovation  Woodland Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-2623","authenticated-orcid":false,"given":"Vadim","family":"Jucaud","sequence":"additional","affiliation":[{"name":"Terasaki Institute for Biomedical Innovation  Woodland Hills California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.04.005"},{"key":"e_1_2_9_3_1","unstructured":"United Network for Organ Sharing \u201cCurrent state of organ donation and transplantation: Liver Transplant trends \u201d United Network for Organ Sharing (2025) (accessed 06\/01\/2025) https:\/\/unos.org\/data\/."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2024.01.014"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.01.030"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201002104\u20108"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13520"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/transplantology2040039"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2022.0018"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hbpd.2024.03.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281\u2010009\u20100155\u20106"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535\u2010016\u20101169\u20101"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389203717666160226145101"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i5.792"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210091"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02155"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/ti.2024.13523"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1020889"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.607953"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101373\u20102"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586\u2010022\u201000118\u20106"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.08.005"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/bios14050225"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering11050476"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI175824"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1223108"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232\u2010022\u201000248\u20100"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101143"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0172677"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12938\u2010024\u201001226\u2010y"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eng.2021.06.020"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122686"},{"key":"e_1_2_9_33_1","article-title":"A Microvascularizedin Vitroliver Model for Disease Modeling and Drug Discovery","author":"Bonanini F.","year":"2024","journal-title":"BioRxiv"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456\u2010022\u201009842\u20109"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122731"},{"key":"e_1_2_9_36_1","article-title":"A Vascularized Liver Microphysiological System Captures Key Features of Hepatic Insulin Resistance and Monocyte Infiltration","author":"Tevonian E. N.","year":"2025","journal-title":"BioRxiv"},{"key":"e_1_2_9_37_1","article-title":"Sox9 links Biliary Maturation to Branching Morphogenesis","author":"Hrncir H. R.","year":"2024","journal-title":"BioRxiv"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2012.06.021"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12172129"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090675"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.06.010"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax5516"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i26.8491"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201004488\u20105"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.21037\/tgh.2020.02.21"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24157"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i34.5429"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119112"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002284RR"},{"key":"e_1_2_9_50_1","volume-title":"Amino Acids in Nutrition and Health: Amino Acids in Systems Function and Health","author":"Hou Y.","year":"2020"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31232"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.710420"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726\u2010010\u20100765\u20102"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.348340.121"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.436"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370215592121"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.021873"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22034"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.97"},{"key":"e_1_2_9_60_1","article-title":"HGF\/c\u2010Met: a Key Promoter in Liver Regeneration","volume":"13","author":"Zhao Y.","year":"2022","journal-title":"Frontiers in Pharmacology"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27328"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25700"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5LC00392J"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010020\u20100342\u20104"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00117"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001377\u20109"},{"key":"e_1_2_9_67_1","volume-title":"Immune Response Activation and Immunomodulation","author":"Castro\u2010Dopico T.","year":"2019"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2024.03.008"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13909"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201001070\u20103"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-96400-3_32"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040\u20104603.2013.tb00507.x"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182483713"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600\u20106143.2003.00135.x"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31817c4cb8"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.06.009"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2024.100749"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/ti.2024.13196"},{"key":"e_1_2_9_79_1","article-title":"Allogeneic HLA Humoral Immunogenicity and the Prediction of Donor\u2010Specific HLA Antibody Development","volume":"13","author":"Jucaud V.","year":"2024","journal-title":"Antibodies (Basel)"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119634010.ch43"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202403560"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2LC00262K"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobme.2021.100309"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.06.013"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2024.101345"},{"key":"e_1_2_9_86_1","article-title":"Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non\u2010parenchymal Liver Cells","author":"Kegel V.","year":"2016","journal-title":"Journal of visualized experiments: JoVE"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74119"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.54"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201045710\u20104"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202521178","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202521178","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202521178","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:04:42Z","timestamp":1783011882000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202521178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,8]]},"references-count":88,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/adma.202521178"],"URL":"https:\/\/doi.org\/10.1002\/adma.202521178","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,8]]},"assertion":[{"value":"2025-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21178"}}