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However, the challenges of replicating the in\u00a0vivo microenvironment, particularly the extracellular matrix, remain important in liver organoid culture. In this study, we explored the roles of Matrigel, a commonly used extracellular matrix component, in the expansion, polarization, and functional maturation of liver organoids derived from human embryonic stem cells (hESCs) under 3-dimensional suspension conditions. Using multiple assays, we demonstrated that a low concentration of Matrigel supported the efficient expansion of hESC-derived hepatoblast organoids by regulating reactive oxygen species (ROS)\u2013autophagy homeostasis through the inhibition of ROS\u2013AMPK\u2013mTOR-mediated excessive autophagy. Moreover, Matrigel induced the polarization of mature hepatocyte organoids differentiated from hESC-derived expandable hepatoblast organoids via activation of the FAK\u2013ERK\u2013AMPK pathway under 3-dimensional suspension conditions. Our findings underscore the importance of integrin signaling in hepatocyte organoid culture and provide insights for the development of artificial, synthetic, bioactive hydrogels for the large-scale production of hepatocytes for clinical applications.<\/jats:p>","DOI":"10.34133\/bmr.0280","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T15:34:58Z","timestamp":1761147298000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":4,"title":["Distinct Roles of Matrigel Enabled the Production of Expandable Hepatoblast and Polarized Hepatocyte Organoids from Human Embryonic Stem Cells under 3-Dimensional Suspension Conditions"],"prefix":"10.34133","volume":"29","author":[{"given":"Haibin","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, \rSouth China 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