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Here, a liver\u2010on\u2010a\u2010chip platform with bioengineered multicellular liver microtissues is developed, composed of four major types of liver cells (hepatocytes, endothelial cells, Kupffer cells, and stellate cells) to implement a human hepatic fibrosis model driven by NAFLD: i) lipid accumulation in hepatocytes (steatosis), ii) neovascularization by endothelial cells, iii) inflammation by activated Kupffer cells (steatohepatitis), and iv) extracellular matrix deposition by activated stellate cells (fibrosis). In this model, the presence of stellate cells in the liver\u2010on\u2010a\u2010chip model with fat supplementation showed elevated inflammatory responses and fibrosis marker up\u2010regulation. Compared to transforming growth factor\u2010beta\u2010induced hepatic fibrosis models, this model includes the native pathological and chronological steps of NAFLD which shows i) higher fibrotic phenotypes, ii) increased expression of fibrosis markers, and iii) efficient drug transport and metabolism. Taken together, the proposed platform will enable a better understanding of the mechanisms underlying fibrosis progression in NAFLD as well as the identification of new drugs for the different stages of NAFLD.<\/jats:p>","DOI":"10.1002\/smll.202007425","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T17:32:20Z","timestamp":1615311140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Bioengineered Multicellular Liver Microtissues for Modeling Advanced Hepatic Fibrosis Driven Through Non\u2010Alcoholic Fatty Liver Disease"],"prefix":"10.1002","volume":"17","author":[{"given":"Hyun\u2010Jong","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Bioengineering Henry Samueli School of Engineering and Applied Sciences University of California\u2010Los Angeles  Los Angeles CA 90095 USA"},{"name":"Center for Minimally Invasive Therapeutics (C\u2010MIT) University 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