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A chitosan\u2010phenol based self\u2010healing hydrogel (CP) integrated with decellularized liver matrix (DLM) is proposed in this study as a 3D gel matrix to carry hepatocytes for possible therapy of liver fibrosis. To mimic the physiological liver microenvironment, DLM is extracted from pigs and mixed with CP hydrogel to generate DLM\u2010CP self\u2010healing hydrogel. Hepatocyte spheroids coated with endothelial cells (ECs) are fabricated using a customized method and embedded in the hydrogel. Hepatocytes injured by exposure to CCl<jats:sub>4<\/jats:sub>\u2010containing medium are used as the in vitro toxin\u2010mediated liver fibrosis model, where the EC\u2010covered hepatocyte spheroids embedded in the hydrogel are co\u2010cultured with the injured hepatocytes. The urea synthesis of the injured hepatocytes reaches 91% of the normal level after 7 days of co\u2010culture, indicating that the hepatic function of injured hepatocytes is rescued by the hybrid spheroid\u2010laden DLM\u2010CP hydrogel. Moreover, the relative lactate dehydrogenase activity of the injured hepatocytes is decreased 49% by the hybrid spheroid\u2010laden DLM\u2010CP hydrogel after 7 days of co\u2010culture, suggesting reduced damage in the injured hepatocytes. The combination of hepatocyte\/EC hybrid spheroids and DLM\u2010CP hydrogel presents a promising therapeutic strategy for hepatic fibrosis.<\/jats:p>","DOI":"10.1002\/mabi.202300411","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T02:58:30Z","timestamp":1707361110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Self\u2010Healing Hydrogel Containing Decellularized Liver Matrix and Endothelial Cell\u2010Covered Hepatocyte Spheroids for Rescue of Injured Hepatocytes"],"prefix":"10.1002","volume":"24","author":[{"given":"Xin\u2010Yu","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Biomechatronics Engineering National Taiwan University  No. 1, Sec. 4, Roosevelt Road Taipei 10617 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Yi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics Engineering National Taiwan University  No. 1, Sec. 4, Roosevelt Road Taipei 10617 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Rong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics Engineering National Taiwan University  No. 1, Sec. 4, Roosevelt Road Taipei 10617 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzong\u2010Jih","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biomechatronics Engineering National Taiwan University  No. 1, Sec. 4, Roosevelt Road Taipei 10617 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richie L. 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