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While previously reported liver\u2010on\u2010a\u2010chip models effectively provide basic structural organization and multilayered arrangements using artificial barriers, they fall short in replicating the higher\u2010order organization of diverse cell types. Herein, we fabricated a membrane\u2010free liver\u2010on\u2010a\u2010chip (MF\u2010LOC) using\u00a0CGRGDS peptide\u2010modified PEGDA hydrogel that not only provides a native\u2010like 3D microenvironment for encapsulated HepG2 (Hepatocytes) cells and NIH\u20103T3 (fibroblasts) but also offers a platform for HUVEC monolayer formation. The immobilization of the CGRGDS peptide on the hydrogel surface, which operates at a nanoscale level to enhance cell adhesion and signaling via integrin binding, strengthens HUVEC adhesion and prevents cell detachment caused by the shear stress of direct tangential flow. In MF\u2010LOC, nutrients easily diffuse through the HUVEC monolayer and hydrogel pores to sustain cell functions. Live\/Dead imaging and cell tracking showed HepG2 clusters associated with neighboring NIH\u20103T3 fibroblasts, with HUVECs forming a surface monolayer which replicate native liver structure. Functional validation confirmed prolonged albumin and urea secretion, with MF\u2010LOC exhibiting sustained CYP1A1 enzyme activity compared to gold standard microsomes, highlighting its ability to replicate liver\u2010like metabolism. MF\u2010LOC has the potential for predicting drug\u2010induced liver injury (DILI) and may provide a powerful platform for disease modeling.<\/jats:p>","DOI":"10.1002\/adhm.202503454","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T06:25:24Z","timestamp":1768976724000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microfabricated Liver\u2010on\u2010a\u2010Chip with Membrane\u2010Free Endothelial\u2013Hepatic Interface for Long\u2010Term Culture and Drug\u2010Induced Liver Injury Modeling"],"prefix":"10.1002","volume":"15","author":[{"given":"Preeti","family":"Sati","sequence":"first","affiliation":[{"name":"Material Science Programme Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"},{"name":"Center For Environmental Science and Engineering Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafat","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"},{"name":"Department of Chemistry Anjabit Singh College, Bikramganj, Veer Kunwar Singh University, Ara, Bihar Bikramganj Bihar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhu","family":"Verma","sequence":"additional","affiliation":[{"name":"Center For Environmental Science and Engineering Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"},{"name":"Department of Chemical Engineering Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Verma","sequence":"additional","affiliation":[{"name":"Center For Environmental Science and Engineering Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"},{"name":"Department of Chemistry Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"},{"name":"Center For Nanosciences Gangwal School of Medical Sciences and Technology Mehta Family Center For Engineering in Medicine Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-2702","authenticated-orcid":false,"given":"Sri","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Material Science Programme Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"},{"name":"Center For Environmental Science and Engineering Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"},{"name":"Department of Chemical Engineering Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"},{"name":"Center For Nanosciences Gangwal School of Medical Sciences and Technology Mehta Family Center For Engineering in Medicine Indian Institute of Technology Kanpur  Kanpur Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101791108"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147215"},{"key":"e_1_2_9_4_1","article-title":"A Standardised Framework To Identify Optimal Animal Models For Efficacy Assessment In Drug Development","volume":"14","author":"Ferreira G. 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