Vascularized Hepatocellular Carcinoma on a Chip to Control Chemoresistance through Cirrhosis, Inflammation and Metabolic Activity

Understanding the effects of inflammation and cirrhosis on regulation drug metabolism during progression hepatocellular carcinoma (HCC) is critical for developing patient-specific treatment strategies. Herein, novel 3D vascularized HCC chips (HCCoCs), composed HCC, endothelial, stellate, Kupffer cells tuned to mimic normal or cirrhotic liver stiffness, are created. controlled by tuning macrophage numbers, impact cytochrome P450-3A4 (CYP3A4) investigated culturing HepG2 transfected with CYP3A4 upregulate expression from baseline. This model allows simulation chemotherapeutic delivery methods such as intravenous injection transcatheter arterial chemoembolization (TACE). It shown that upregulation metabolic activity, incorporation inflammation, increases vascular permeability due upregulated inflammatory cytokines leading significant variability in efficacy. Specifically, it further modulation activity TACE doxorubicin provides an additional improvement response reduces chemotherapy-associated endothelial porosity increase. The HCCoCs have utility uncovering tumor microenvironment cancer properties, therapeutics,