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These biomechanical alterations have long been considered as pathological consequences. Recently, growing evidence proposes that these alternations result in the fibrotic biomechanical microenvironment, which drives the activation of hepatic stellate cells (HSCs). Here, an inorganic ascorbic acid\u2010oxidase (AAO) mimicking nanozyme loaded with liquiritigenin (LQ) is developed to trigger remodeling of the fibrotic biomechanical microenvironment. The AAO mimicking nanozyme is able to consume intracellular ascorbic acid, thereby impeding collagen I deposition by reducing its availability. Simultaneously, LQ inhibits the transcription of lysyl oxidase like 2 (LOXL2), thus impeding collagen I crosslinking. Through its synergistic activities, the prepared nanosystem efficiently restores the fibrotic biomechanical microenvironment to a near\u2010normal physiological condition, promoting the quiescence of HSCs and regression of fibrosis. This strategy of remodeling the fibrotic biomechanical microenvironment, akin to \u201cpulling the rug out from under\u201d, effectively treats hepatic fibrosis in mice, thereby highlighting the importance of tissue biomechanics and providing a potential approach to improve hepatic fibrosis treatment.<\/jats:p>","DOI":"10.1002\/adma.202406590","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T01:38:02Z","timestamp":1729042682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pulling the Rug Out from Under: Biomechanical Microenvironment Remodeling for Induction of Hepatic Stellate Cell Quiescence"],"prefix":"10.1002","volume":"36","author":[{"given":"Haobo","family":"Wang","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Drug Delivery &amp; High\u2010Efficiency School of Pharmaceutical Science and Technology Faculty of Medicine Tianjin University  Tianjin 300072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"You","sequence":"additional","affiliation":[{"name":"Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering Yong Loo Lin School of Medicine and College of Design and Engineering National University of Singapore  Singapore 119074 Singapore"},{"name":"Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore  Singapore 117599 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Kang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Drug Delivery &amp; 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