A Functional Human Liver Tissue Model: 3D Bioprinted Co-culture Discoids

Abstract

To reduce costs and delays related to developing new and effective drugs, there is a critical need for improved human liver tissue models. Here we describe an approach for 3D bioprinting functional human liver tissue models, in which we fabricate disc-shaped structures (discoids) 200 {\mu}m in thickness and 1-3 mm in diameter, embedded in a highly permeable support medium made from packed microgels. We demonstrate that the method is precise, accurate, and scalable; up to 100 tissues per hour can be manufactured with a variability and error in diameter of about 4%. Histologic and immunohistochemical evaluation of printed discs reveal self-organization, cell cohesion, and key liver marker expression. During the course of 3-4 weeks in culture, the tissues stably synthesize albumin and urea at high levels, outperforming spheroid tissue models. We find the tissues express more than 100 genes associated with molecular absorption, distribution, metabolism, and excretion (ADME) at levels within the range of human liver. The liver tissue models exhibit enzymatic formation of metabolites after exposure to multiple test compounds. Together, these results demonstrate the promise of 3D printed discoids for pharmacological and toxicological applications.