A 3D bio-printed spheroids based perfusion in vitro liver on chip for drug toxicity assays

Abstract

Liver is the foremost organ of human being for drug metabolism, and it played a significant role in toxicity evaluation of drugs. Establishing a liver model in vitro can accelerate the process of the drug screening and new drug research and development. We provide a 3D printing based hepatic sinusoid-on-a-chip microdevice that reconstitutes organ-level liver functions to create a drug screening model of toxicity evaluation on chip. The microfluidic device, which recapitulates the hepatic sinusoid microenvironment, consists of PET polyporous membranes which mimic the perisinusoidal space, and experience fluid flow to mimic the hepatic arterial capillaries. The PET membrane was used to separate the hepatocyte and endotheliocyte. The endotheliocyte was cultured on the downside of the membrane and the hepatocyte were 3D seeded on the membrane via the 3D printer. This device was used to reproduce the in vitro liver model for drug toxicity assays. The expression of several biomarkers of liver was compared with the monoculture and 2D cultured conditions, and the results reveal that this organ-on-a-chip microdevice mimics the drug hepatoxicity that has not been possible by 2D cell-based and animal models, providing a useful platform for screening the drugs and developing an effective therapy in hepatopathy.