Chou, Xin YuXin YuChouCheng, Kai YiKai YiChengYin, Wei RongWei RongYinCheng, Tzong-JihTzong-JihChengChen, Richie L. C.Richie L. C.ChenSHAN-HUI HSUYUNG-TE HOU2024-03-012024-03-012024-01-0116165187https://scholars.lib.ntu.edu.tw/handle/123456789/640167Liver fibrosis occurs in many chronic liver diseases, while severe fibrosis can lead to liver failure. A chitosan-phenol based self-healing 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-CP self-healing hydrogel. Hepatocyte spheroids coated with endothelial cells (ECs) are fabricated using a customized method and embedded in the hydrogel. Hepatocytes injured by exposure to CCl4-containing medium are used as the in vitro toxin-mediated liver fibrosis model, where the EC-covered hepatocyte spheroids embedded in the hydrogel are co-cultured with the injured hepatocytes. The urea synthesis of the injured hepatocytes reaches 91% of the normal level after 7 days of co-culture, indicating that the hepatic function of injured hepatocytes is rescued by the hybrid spheroid-laden DLM-CP hydrogel. Moreover, the relative lactate dehydrogenase activity of the injured hepatocytes is decreased 49% by the hybrid spheroid-laden DLM-CP hydrogel after 7 days of co-culture, suggesting reduced damage in the injured hepatocytes. The combination of hepatocyte/EC hybrid spheroids and DLM-CP hydrogel presents a promising therapeutic strategy for hepatic fibrosis.endecellularized liver matrix | endothelial cells | hepatocyte spheroids | liver fibrosis | self-healing hydrogel[SDGs]SDG3journal article10.1002/mabi.202300411383262192-s2.0-85184702485https://api.elsevier.com/content/abstract/scopus_id/85184702485