{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:20:01Z","timestamp":1782933601105,"version":"3.54.5"},"reference-count":67,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["1R01AA027189-01A1"],"award-info":[{"award-number":["1R01AA027189-01A1"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM104320"],"award-info":[{"award-number":["P20 GM104320"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008114","name":"University of Nebraska-Lincoln","doi-asserted-by":"publisher","award":["Nebraska Research Initiative-Systems Grant"],"award-info":[{"award-number":["Nebraska Research Initiative-Systems Grant"]}],"id":[{"id":"10.13039\/100008114","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Chronic liver disease is characterized by progressive hepatic fibrosis leading to the formation of cirrhosis irrespective of the etiology with no effective treatment currently available. Liver stiffness (LS) is currently the best clinical predictor of this fibrosis progression irrespective of the etiology. LS and hepatocytes-nonparenchymal cells (NPC) interactions are two variables known to be important in regulating hepatic function during liver fibrosis, but little is known about the interplay of these cues. Here, we use polydimethyl siloxane (PDMS) based substrates with tunable mechanical properties to study how cell\u2013cell interaction and stiffness regulates hepatocytes function. Specifically, primary rat hepatocytes were cocultured with NIH-3T3 fibroblasts on soft (2 kPa) and stiff substrates that recreates physiologic (2 kPa) and cirrhotic liver stiffness (55 kPa). Urea synthesis by primary hepatocytes depended on the presence of fibroblast and was independent of the substrate stiffness. However, albumin synthesis and Cytochrome P450 enzyme activity increased in hepatocytes on soft substrates and when in coculture with a fibroblast. Western blot analysis of hepatic markers, E-cadherin, confirmed that hepatocytes on soft substrates in coculture promoted better maintenance of the hepatic phenotype. These findings indicate the role of stiffness in regulating the hepatocytes interactions with NPCs necessary for maintenance of hepatocytes function.<\/jats:p>","DOI":"10.3390\/biology10050408","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T11:06:01Z","timestamp":1620212761000},"page":"408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Exploring Interactions between Primary Hepatocytes and Non-Parenchymal Cells on Physiological and Pathological Liver Stiffness"],"prefix":"10.3390","volume":"10","author":[{"given":"Vaishaali","family":"Natarajan","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youra","family":"Moeun","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0282-0411","authenticated-orcid":false,"given":"Srivatsan","family":"Kidambi","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"},{"name":"The Fred &amp; Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"},{"name":"Nebraska Center for the Prevention of Obesity Diseases, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, Lincoln, NE 68588, USA"},{"name":"Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1159\/000374098","article-title":"Hepatic Fibrosis: Emerging Therapies","volume":"33","author":"Friedman","year":"2015","journal-title":"Dig. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.jhep.2015.02.039","article-title":"Hepatic fibrosis: Concept to treatment","volume":"62","author":"Trautwein","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/gutjnl-2014-306842","article-title":"Pathobiology of liver fibrosis: A translational success story","volume":"64","author":"Lee","year":"2015","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s12072-010-9240-0","article-title":"Non-invasive assessment of liver fibrosis in chronic hepatitis C","volume":"5","author":"Castera","year":"2011","journal-title":"Hepatol. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.cgh.2007.06.012","article-title":"Assessment of hepatic fibrosis with magnetic resonance elastography","volume":"5","author":"Yin","year":"2007","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/hep.22007","article-title":"Acute viral hepatitis increases liver stiffness values measured by transient elastography","volume":"47","author":"Arena","year":"2008","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1136\/gut.2005.069153","article-title":"Diagnosis of cirrhosis by transient elastography (FibroScan): A prospective study","volume":"55","author":"Foucher","year":"2006","journal-title":"Gut"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1002\/hep.29612","article-title":"Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality","volume":"67","author":"Jansen","year":"2018","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R266","DOI":"10.1186\/cc10543","article-title":"Increased liver stiffness denotes hepatic dysfunction and mortality risk in critically ill non-cirrhotic patients at a medical ICU","volume":"15","author":"Koch","year":"2011","journal-title":"Crit. Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/apt.12561","article-title":"Food intake increases liver stiffness measurements and hampers reliable values in patients with chronic hepatitis B and healthy controls: The PROLIFICA experience in The Gambia","volume":"39","author":"Lemoine","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jhep.2009.11.018","article-title":"Liver stiffness is directly influenced by central venous pressure","volume":"52","author":"Millonig","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1055\/s-2001-17551","article-title":"Hepatic blood flow regulation by stellate cells in normal and injured liver","volume":"21","author":"Rockey","year":"2001","journal-title":"Semin Liver Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3892\/ijmm.2013.1544","article-title":"Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats","volume":"33","author":"Arima","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1053\/gast.2001.25540","article-title":"Nonalcoholic fatty liver disease: Predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese","volume":"121","author":"Dixon","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wells, R.G. (2016). Location, location, location: Cell-level mechanics in liver fibrosis. Hepatology.","DOI":"10.1002\/hep.28519"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.bbadis.2013.02.007","article-title":"Tissue mechanics and fibrosis","volume":"1832","author":"Wells","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1172\/JCI93561","article-title":"Mechanosensing and fibrosis","volume":"128","author":"Tschumperlin","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sato, K., Kennedy, L., Liangpunsakul, S., Kusumanchi, P., Yang, Z., Meng, F., Glaser, S., Francis, H., and Alpini, G. (2019). Intercellular Communication between Hepatic Cells in Liver Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092180"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.tox.2008.06.013","article-title":"Hepatic fibrosis\u2014overview","volume":"254","author":"Friedman","year":"2008","journal-title":"Toxicology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.276.5309.60","article-title":"Liver regeneration","volume":"276","author":"Michalopoulos","year":"1997","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hurrell, T., Kastrinou-Lampou, V., Fardellas, A., Hendriks, D.F.G., Nordling, A., Johansson, I., Baze, A., Parmentier, C., Richert, L., and Ingelman-Sundberg, M. (2020). Human Liver Spheroids as a Model to Study Aetiology and Treatment of Hepatic Fibrosis. Cells, 9.","DOI":"10.3390\/cells9040964"},{"key":"ref_23","first-page":"1753","article-title":"The interplay between hepatic stellate cells and hepatocytes in an in vitro model of NASH","volume":"29","author":"Giraudi","year":"2015","journal-title":"Toxicol. Vitro Int. J. Publ. Assoc. BIBRA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.yexmp.2014.12.006","article-title":"The importance of the interaction between hepatocyte and hepatic stellate cells in fibrogenesis induced by fatty accumulation","volume":"98","author":"Giraudi","year":"2015","journal-title":"Exp. Mol. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell (Cambridge, MA, United States)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5481493","DOI":"10.1155\/2016\/5481493","article-title":"Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes","volume":"2016","author":"Cozzolino","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7389","DOI":"10.1016\/j.biomaterials.2011.06.042","article-title":"Regulation of hepatic stem\/progenitor phenotype by microenvironment stiffness in hydrogel models of the human liver stem cell niche","volume":"32","author":"Lozoya","year":"2011","journal-title":"Biomaterials"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kidambi, S. (2020). Chapter 55. Stiffness and Hepatocytes Function In Vitro in \u201cLiver Elastography-Clinical Use and Interpretation\u201d. Liver Elastography Clin. Use Interpret.","DOI":"10.1007\/978-3-030-40542-7_55"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.bbrc.2018.04.142","article-title":"Matrix stiffness regulate apoptotic cell death in HIV-HCV co-infected hepatocytes: Importance for liver fibrosis progression","volume":"500","author":"Ganesan","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"80956","DOI":"10.1039\/C5RA15208A","article-title":"Substrate stiffness regulates primary hepatocyte functions","volume":"5","author":"Natarajan","year":"2015","journal-title":"Rsc Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28450","article-title":"Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha","volume":"64","author":"Desai","year":"2016","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/bit.20328","article-title":"Engineering hepatocellular morphogenesis and function via ligand-presenting hydrogels with graded mechanical compliance","volume":"89","author":"Semler","year":"2005","journal-title":"Biotechnol. Bioeng."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jmbbm.2015.10.016","article-title":"Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology","volume":"55","author":"Deegan","year":"2015","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1089\/ten.tea.2012.0681","article-title":"Characterizing the effects of heparin gel stiffness on function of primary hepatocytes","volume":"19","author":"You","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.biomaterials.2008.10.055","article-title":"Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers","volume":"30","author":"Chen","year":"2009","journal-title":"Biomaterials"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1525-1594.2012.01546.x","article-title":"Matrix Stiffness in Three-Dimensional Systems Effects on the Behavior of C3A Cells","volume":"37","author":"Huang","year":"2013","journal-title":"Artif. Organs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1073\/pnas.85.7.2161","article-title":"Cell-cell and cell-matrix interactions differentially regulate the expression of hepatic and cytoskeletal genes in primary cultures of rat hepatocytes","volume":"85","author":"Robinson","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/jcp.1041510308","article-title":"Switching from differentiation to growth in hepatocytes: Control by extracellular matrix","volume":"151","author":"Mooney","year":"1992","journal-title":"J. Cell. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0070-2153(05)72004-4","article-title":"Regulation of hepatocyte cell cycle progression and differentiation by type I collagen structure","volume":"72","author":"Hansen","year":"2006","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1091\/mbc.e05-09-0871","article-title":"Type I collagen structure regulates cell morphology and EGF signaling in primary rat hepatocytes through cAMP-dependent protein kinase A","volume":"17","author":"Fassett","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_41","first-page":"3768","article-title":"T-cadherin modulates hepatocyte functions in vitro","volume":"22","author":"Khetani","year":"2008","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/hep.20351","article-title":"Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling","volume":"40","author":"Khetani","year":"2004","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/(SICI)1097-4636(199702)34:2<189::AID-JBM8>3.0.CO;2-M","article-title":"Controlling cell interactions by micropatterning in co-cultures: Hepatocytes and 3T3 fibroblasts","volume":"34","author":"Bhatia","year":"1997","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/00002480-199907000-00005","article-title":"Endothelial cell behavior on vascular prosthetic grafts: Effect of polymer chemistry, surface structure, and surface treatment","volume":"45","author":"Marois","year":"1999","journal-title":"ASAIO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/S0142-9612(98)00250-6","article-title":"PDMS-based polyurethanes with MPEG grafts: Synthesis, characterization and platelet adhesion study","volume":"20","author":"Park","year":"1999","journal-title":"Biomaterials"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1163\/156856299X00333","article-title":"Novel polyisobutylene\/polydimethyl siloxane bicomponent networks: III. Tissue compatibility","volume":"10","author":"Sherman","year":"1999","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1163\/156856292X00475","article-title":"Cytocompatibility study of NHLBI primary reference materials using human endothelial cells","volume":"3","author":"Bordenave","year":"1992","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1097-4636(199821)43:1<1::AID-JBM1>3.0.CO;2-T","article-title":"Influence of silicone (PDMS) surface texture on human skin fibroblast proliferation as determined by cell cycle analysis","volume":"43","author":"Whitesides","year":"1998","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/jbm.820280603","article-title":"In vitro study of the intrinsic toxicity of synthetic surfaces to cells","volume":"28","author":"Ertel","year":"1994","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/masy.200350913","article-title":"Synthesis and properties of poly(butylene terephthalate)-poly(ethylene oxide)-poly(dimethylsiloxane) block copolymers","volume":"199","author":"Dahrouch","year":"2003","journal-title":"Macromol. Symp."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1021\/ma001785w","article-title":"Poly(dimethylsilylenemethylene-co- dimethylsiloxane): A Regularly Alternating Copolymer of Poly(dimethylsiloxane) and Poly(dimethylsilylenemethylene)","volume":"34","author":"Interrante","year":"2001","journal-title":"Macromolecules"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/cld.186","article-title":"Noninvasive assessment of patients with alcoholic liver disease","volume":"2","author":"Mueller","year":"2013","journal-title":"Clin. Liver Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2147\/HMER.S7394","article-title":"Liver stiffness: A novel parameter for the diagnosis of liver disease","volume":"2","author":"Mueller","year":"2010","journal-title":"Hepatic Med. Evid. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1163\/156856298X00695","article-title":"Probing heterotypic cell interactions: Hepatocyte function in microfabricated co-cultures","volume":"9","author":"Bhatia","year":"1998","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/53.1.261","article-title":"Epithelial cell cultures from normal glandular tissue of mice","volume":"53","author":"Owens","year":"1974","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/BF02619590","article-title":"Selective elimination of fibroblasts from cultures of normal human melanocytes","volume":"20","author":"Halaban","year":"1984","journal-title":"Vitro"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0040-8166(80)90033-6","article-title":"The isolation and characterization in vitro of normal epithelial cells, endothelial cells and fibroblasts from rat urinary bladder","volume":"12","author":"Pauli","year":"1980","journal-title":"Tissue Cell"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Rubio, S., Cazares, O., Macias, H., and Hinck, L. (2020). Generation of Mosaic Mammary Organoids by Differential Trypsinization. J. Vis. Exp. JoVE.","DOI":"10.3791\/60742"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"529","DOI":"10.2217\/rme-2016-0039","article-title":"Human-derived feeder fibroblasts for the culture of epithelial cells for clinical use","volume":"11","author":"Morgan","year":"2016","journal-title":"Regen. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nmat3889","article-title":"Mechanical memory and dosing influence stem cell fate","volume":"13","author":"Yang","year":"2014","journal-title":"Nat. Mater"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.ultrasmedbio.2013.01.009","article-title":"Liver fibrosis assessment using transient elastography guided with real-time B-mode ultrasound imaging: A feasibility study","volume":"39","author":"Mak","year":"2013","journal-title":"Ultrasound Med. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e201800177","DOI":"10.1002\/jbio.201800177","article-title":"Feasibility study of using the dispersion of surface acoustic wave impulse for viscoelasticity characterization in tissue mimicking phantoms","volume":"12","author":"Zhou","year":"2019","journal-title":"J. Biophotonics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0142-9612(96)85576-1","article-title":"Culture matrix configuration and composition in the maintenance of hepatocyte polarity and function","volume":"17","author":"Moghe","year":"1996","journal-title":"Biomaterials"},{"key":"ref_64","first-page":"174","article-title":"Hepatocyte function and extracellular matrix geometry: Long-term culture in a sandwich configuration","volume":"3","author":"Dunn","year":"1989","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/brv.12650","article-title":"The science and engineering of stem cell-derived organoids-examples from hepatic, biliary, and pancreatic tissues","volume":"96","author":"Ogoke","year":"2021","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lee, J.Y., Han, H.J., Lee, S.J., Cho, E.H., Lee, H.B., Seok, J.H., Lim, H.S., and Son, W.C. (2020). Use of 3D Human Liver Organoids to Predict Drug-Induced Phospholipidosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082982"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1039\/C8LC00869H","article-title":"In situ differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system","volume":"18","author":"Wang","year":"2018","journal-title":"Lab chip"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/5\/408\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:57:16Z","timestamp":1760162236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/5\/408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":67,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["biology10050408"],"URL":"https:\/\/doi.org\/10.3390\/biology10050408","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]}}}