Involved in detoxifying and metabolizing compounds, the liver regulates how drugs interact with target and off-target organs. Most orally-ingested drugs find their way to the liver, and the interactions between these compounds and liver cells help determine dosage levels. The liver consists of Kupffer cells, sinusoidal endothelial cells, and stellate cells, which contribute to the numerous intricate metabolic pathways conducted by the organ.
Typical static cultures of liver cells cannot mimic organ-level physiology due to poor cell morphology and functionality as well as a lack of cell-to-cell signaling. Since the liver has multiple cell types, two-dimensional static models also limit the number of cell systems that can be cultured and analyzed at once. Assessing hepatotoxicity on static in vitro models and animal in vivo models has also been shown as problematic due to the poor translatability of data from these models to human parameters.
By culturing liver organs in three-dimensional microfluidic platforms, the mechanisms of drugs flowing through the organ can be observed. Since the microenvironment accounts for parameters like sheer stress and barrier integrity, which are key features found in vivo, acquired data is more translatable to human trials. Hepatotoxic compounds can be screened with more accuracy, which accelerates drug development workflows.