Inflammation-on-a-chip : a microphysiological human liver mode

Microphysiological organ-on-a-chip models enter the stage as an enhanced in vitro method to emulate physiological processes ex vivo. This approach offers new possibilities to study systemic inflammatory diseases like sepsis and could be a promising tool to investigate the pathophysiological role of organs, such as the liver, during inflammation under humanized conditions. The objective of this work was the establishment of a human liver-on-a-chip and its application as a model of inflammatory hepatic dysfunction. In the first study, four major cell types of the liver were integrated in the Multi Organ Tissue Flow (MOTiF) biochip and examined by functional as well as morphological characteristics. To verify the applicability of the liver-on-a-chip model as a new biomedical research tool we investigated toll-like receptor (TLR)-mediated inflammation. Interestingly, hepatic damage was prevented by integration of circulating monocytes, which resulted in inflammatory resolution. To improve utilization of organ-on-a-chip applications we developed novel protocols for hypothermic storage of liver-on-a-chip models to maintain their microstructure after assembly. The study confirmed that the preservation of the liver model in an adapted formulation of the TiProtec® storage solution is possible for up to two days at 4 °C. Our hepatic model featured characteristics of human tissue samples and clinical observations during liver inflammation. This model has the potential to become a valuable alternative to overcome the limitations in translational research and will help to close the gap between conventional cell culture and animal experimentation.