Self‐Healable Hydrogel for Regression of Liver Fibrosis

Liver fibrosis is considered as a wound healing process in the presence of chronic hepatic injury. A hydrogel (CPDP) based on chitosan-phenol that undergoes fast gelling and owns self-healing and injectable properties was investigated for the effect on regression of liver fibrosis. For the purpose, we established both in vitro and in vivo liver fibrosis models and implanted CPDP hydrogel into the injured liver. The CPDP hydrogel not only provided a suitable microenvironment for hepatocyte spheroids, but also demonstrated a potential for the hepatocyte spheroid-embedded system to mimic the liver tissue in vitro. Furthermore, the urea synthesis of injured hepatocytes cultured on hepatocyte spheroid-embedded CPDP hydrogel was 1.12 times higher than that on hepatocyte spheroid-embedded collagen hydrogel after 7 days of culture, indicating that CPDP hydrogel effectively rescued hepatic function in the injured hepatocytes. Moreover, the hepatic injury was alleviated with improved hepatic function in the liver fibrosis model in vivo. A reduction of approximately 28% in serum AST/ALT ratios and a 70% decrease in the fibrotic area suggested the regression of liver fibrosis after 2 weeks of CPDP hydrogel administration. These findings suggest that CPDP hydrogel holds promise for applications in liver tissue engineering.