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The present study evaluated the therapeutic efficacy of a hepatocyte spheroid\u2010laden composite hydrogel comprising a chitosan\u2013phenol self\u2010healing hydrogel (CPDP), decellularized liver matrix (DLM), and tannic acid (TA), assessing its effects in both in vitro and in vivo rat models of MASLD. This design combined the rapid gelation, self\u2010healing ability, and injectability of CPDP, the antioxidant properties of TA, the high biocompatibility of DLM and the ability of hepatocyte spheroids to mimic the liver microenvironment and maintain hepatic function. Our results demonstrated that the composite self\u2010healing hydrogel incorporating TA (0.1 wt%) and DLM (0.002 wt%) laden further with hepatocyte spheroids (\u201cTA\u2010CDS\u201d) exhibited significant therapeutic effects, including reductions in body weight, liver weight, and liver\u2010to\u2010body\u2010weight ratio in MASLD rats. After 2 weeks of treatment, TA\u2010CDS markedly improved hepatic function and lipid metabolism, as evidenced by favorable changes in serum biochemical parameters, including liver enzymes and lipid profiles. This study underscores the short\u2010term therapeutic efficacy of the hepatocyte spheroid\u2010laden composite self\u2010healing hydrogel for MASLD therapy. Further studies are warranted to evaluate its long\u2010term safety, degradation behavior, tissue response, and therapeutic efficacy before clinical translation.<\/jats:p>","DOI":"10.1002\/adhm.71783","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:53:57Z","timestamp":1790661237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatocyte Spheroid\u2010Laden Self\u2010Healing Hydrogel Containing Decellularized Liver Matrix and Tannic Acid: A Potential Treatment for Metabolic\u2010Dysfunction\u2010Associated Steatotic Liver Disease"],"prefix":"10.1002","author":[{"given":"Xin\u2010Yu","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Biomechatronics Engineering National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Rong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics Engineering National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutaro","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application (CiRA) Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Osafune","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application (CiRA) Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3399-055X","authenticated-orcid":false,"given":"Shan\u2010hui","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Polymer Science and Engineering National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4978-9829","authenticated-orcid":false,"given":"Yung\u2010Te","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics Engineering National Taiwan University  Taipei Taiwan"},{"name":"Animal Resource Center National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12051852"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168\u20108278(02)00429\u20104"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13081264"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1343587"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/rpsppr\/rqac001"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46070376"},{"issue":"2","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","DOI":"10.14309\/ctg.0000000000000806","article-title":"Healthy Lifestyle and Metabolic Dysfunction\u2010Associated Steatotic Liver Disease: A Study of the Efficacy of Fatty Liver Regression","volume":"16","author":"Wang J.","year":"2025","journal-title":"Clinical and Translational Gastroenterology"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1419384"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121067"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.2c00967"},{"issue":"9","key":"e_1_2_13_13_1","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1021\/acsbiomaterials.9b00745","article-title":"Liver Tissue Engineering: Challenges and Opportunities","volume":"5","author":"Agarwal T.","year":"2019","journal-title":"ACS Biomaterials Science & Engineering"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202300411"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.molmet.2018.11.001","article-title":"Tannic Acid, a Novel Histone Acetyltransferase Inhibitor, Prevents Non\u2010Alcoholic Fatty Liver Disease both In Vivo and In Vitro Model","volume":"19","author":"Chung M. 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