A 3D Bioprinted In Vitro Model of Human Liver for the Study of Liver Fibrosis

Liver fibrosis , a characteristic of most liver diseases, results from chronic liver injury in conjunction with the accumulation of extracellular matrix (ECM) proteins 1,2. Despite the critical role of liver tissue microenvironmental changes in the development and progression of liver fibrosis3,4, the cellular mechanisms underlying hepatic dysfunction in liver fibrosis in response to mechanical cues ( e.g., ECM stiffness and dynamic flow) remain elusive. In this study, we fabricated three-dimensional (3D) perfusable liver models with ECM stiffness values mimicking those in the healthy vs. fibrotic states of the human liver. Engineered liver models retained viability, proliferation, and function of both human endothelial and hepatic cells during a 2- week culture period. Further, the effect s of hepatocyte-endothelial cell coculture and dynamic flow conditions (static vs. rocking) were studied in our 3D bioprinted model of liver fibrosis. Finally, a pilot perfu sion study was successfully conducted using a customized bioreactor system, demonstrating the robust potential of this 3D bioprinted liver platform to be utilized for intensive in vitro studies of liver diseases.