HGF/heparin-immobilized decellularized liver matrices as novel hepatic patches for hepatocyte regeneration in an acute liver injury model

Abstract

Although liver cirrhosis is a common condition and cause of death, treatment methods remain limited; for example, instead of facilitating hepatocyte regeneration, they may only alleviate or resolve symptoms. Notably, studies have indicated that liver fibrosis is reversible; moreover, prompt and appropriate treatment can prevent liver fibrosis from developing into liver cirrhosis. In this study, a hepatocyte growth factor (HGF)/heparin-immobilized decellularized liver matrix (HGF/heparin-DLM) was fabricated for hepatocyte regeneration in a model of acute d-galactosamine–induced liver injury. Various initial concentrations (0.2, 0.4, 0.6, 0.8, 1 mg/mL) were used for the immobilization of heparin on DLM films. The amounts of immobilized heparin on the DLM films at these concentrations were 4.7 ± 1.1, 12.2 ± 2.7, 18.2 ± 5.1, 21.9 ± 3.8, and 29.1 ± 1.1 μg/cm2, respectively. The relative viability and albumin synthesis of the hepatocytes on the HGF/heparin-DLM films were 19% and 26% greater than those of the hepatocytes cultured in regular petri dishes on day 3, respectively. The LDH and albumin of the injured hepatocytes on the HGF/heparin-DLM films were 95% lower and almost 2.7 times higher than those cultured in regular petri dishes on day 5, respectively. In sum, the HGF/heparin-DLM films were effective in hepatocyte culturing and repairing d-galactosamine–induced hepatocyte damage. Thus, they have potential for future clinical applications.