Drug discovery for complex liver diseases faces alarming attrition rates. The lack of non-clinical models that 
recapitulate key aspects of liver (patho)-physiology is likely contributing to the inefficiency of developing 
effective treatments. Of particular notice is the common omission of an organized microvascular component 
despite its importance in maintaining liver function and its involvement in the development of several 
pathologies. Increasing the complexity of in vitro models is usually associated with a lack of scalability and 
robustness which hinders their implementation in drug development pipelines. Here, we describe a 
comprehensive liver MPS model comprising stellates, liver-derived endothelial cells and hepatocytes
conceived within a scalable and automated platform. We show that endothelial cells self-organize in a 
microvascular network when co-cultured with stellates in a hydrogel. In a tri-culture, hepatocytes polarize 
accordingly, with a basolateral side facing blood vessels and an apical side facing bile-canaliculi-like structures.
Stellates interact and surround the hollow microvessels. Steatosis was induced by exogenous administration 
of fatty acids which could be prevented by co-administration of firsocostat. Administration of TGF-ß resulted 
in an activated stellate cells phenotype which could be prevented by the co-administration of SB-431542. 
The model was implemented on a microtiter plate format comprising 64 chips which enabled the 
development of a fully automated, multiplexed fibrosis assay with a robust Z’ factor suitable for highthroughput applications.