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However, the extracellular matrix (ECM) scaffold used for such models often does not mimic either the complex composition or the nanofibrous topography of native liver ECM. Thus, here novel methods are developed to electrospin decellularized porcine liver ECM (PLECM) and collagen I into nano\u2010 and microfibers (\u2248200\u20131000\u00a0nm) without synthetic polymer blends. Primary human hepatocytes (PHHs) on nanofibers in monoculture or in coculture with nonparenchymal cells (3T3\u2010J2 embryonic fibroblasts or primary human liver endothelial cells) display higher albumin secretion, urea synthesis, and cytochrome\u2010P450 1A2, 2A6, 2C9, and 3A4 enzyme activities than on conventionally adsorbed ECM controls. PHH functions are highest on the collagen\/PLECM blended nanofibers (up to 34\u2010fold higher CYP3A4 activity relative to adsorbed ECM) for nearly 7 weeks in the presence of the fibroblasts. In conclusion, it is shown for the first time that ECM composition and topography synergize to enhance and stabilize PHH functions for several weeks in vitro. The nanofiber platform can prove useful for the above applications and to elucidate cell\u2010ECM interactions in the human liver.<\/jats:p>","DOI":"10.1002\/adhm.202202302","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T12:13:36Z","timestamp":1679487216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Decellularized Liver Nanofibers Enhance and Stabilize the Long\u2010Term Functions of Primary Human Hepatocytes In Vitro"],"prefix":"10.1002","volume":"12","author":[{"given":"Jennifer S.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Illinois at Chicago  Chicago IL 60607 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liszt Y. 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