Modeling Liver Biology and the Tissue Response to Injury in Bioprinted Human Liver Tissues

Abstract

The rapid advancement of additive manufacturing technologies and their extension into biological systems have led to the emergence of a new category of cell-based models, namely bioprinted tissues. By combining automation and spatially controlled deposition of distinct components, such as cells, hydrogels, and mixtures thereof, the tissue engineer can now design and build tissues with far more control over the architecture of the end product. Bioprinted human liver tissues (BHLT) were one of the first commercial examples of a tissue model fabricated from three or more specific cell types using a custom-built robotic bioprinting platform. Significant progress has been made toward characterizing BHLT and evaluating their performance in a broad spectrum of applications, including in vitro safety and efficacy testing, and disease modeling. Like many multicellular and/or three-dimensional liver tissue models, BHLT exhibit enhanced longevity and persistent liver functions (protein synthesis, metabolism) compared with traditional monocellular or two-dimensional systems. BHLT are a compelling option for many in vitro applications due to several factors: (1) they contain cell–cell interfaces with direct contact between multiple cell types without interference from culture surfaces (polystyrene or polymeric membranes); (2) they have sufficient biomass to enable isolation of nucleic acids or proteins for use in genomic or proteomic analyses; and (3) they are compatible with histology techniques and thus enable detection of outcomes that require histological endpoints for interpretation, such as liver fibrosis and nonalcoholic steatohepatitis. The advantages and limitations of BHLT are highlighted herein through a series of exemplary case studies and related discussion.