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To advance preclinical toxicology research, we developed an\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      liver model using HepG2 for toxic evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The model was constructed based on the extracellular matrix. We assessed its long-term stability by monitoring the morphological change and anabolic capacity for 2\u00a0weeks, with functional analyses including albumin\/urea production, lipid accumulation with Nile red staining, bile secretion with CLF signal, and transporter\/enzyme expression including PGP, MRP2, BSEP, and CYP3A4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The model could be maintained for at least 10\u00a0days with enhanced hepatic synthetic functions indicated by albumin and urea nitrogen. Compared with the two-dimensional (2D) cultures, 3D culture exhibited enhanced lipid accumulation and biliary excretion. Key hepatic transporters PGP, MRP2, and BSEP and the metabolic enzyme cytochrome P450 3A4 were expressed between day 5 and 7. Single-exposure induced measurable apoptosis, mitochondrial disfunction and viability assays, while repeated treatment replicated impaired bile acid transport by reduced CLF intensity, and cytotoxicity with elevated AST, ALT, and decreased survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our 3D model surpasses conventional 2D systems in culture duration and functional complexity. It is suitable for DILI prediction after single- and repeated- treatment, which makes it particularly valuable for preclinical drug screening.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271251350797","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T14:54:31Z","timestamp":1752591271000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Establishment and validation of an\n                    <i>in vitro<\/i>\n                    liver model based extracellular matrix for hepatotoxicity prediction"],"prefix":"10.1177","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-7362","authenticated-orcid":false,"given":"Yue","family":"Yu","sequence":"first","affiliation":[{"name":"National Institutes for Food and Drug Control"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3060-3362","authenticated-orcid":false,"given":"Haodong","family":"Zhong","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control"},{"name":"China Pharmaceutical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5828-4485","authenticated-orcid":false,"given":"Qianyi","family":"Niu","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control"},{"name":"Shenyang Pharmaceutical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manman","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control"},{"name":"State Key Laboratory of Drug Regulatory Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobing","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control"},{"name":"State Key Laboratory of Drug Regulatory Science"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13062-020-00285-0"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.938807"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.8b00054"},{"key":"e_1_3_6_5_2","unstructured":"FDA. 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