Figure 5.

Different possible modes of operation of liver microphysiological systems (MPS) based on circulation of cell culture medium. Developed systems can differ from each other on operational levels that relate to the way cell culture medium is supplied to the cell culture unit. These operational levels have a strong impact in the kinetics of cellular metabolism and energetics due to differences in cellular exposure to nutrients, metabolites, and drugs, which eventually affect system response to drugs.63 (a) Medium can be recirculated and completely changed every 2–3 days throughout the operation time.53 (b) Soluble medium components or compounds can be supplied between media changes.39 (c) Fresh medium can be continuously perfused into the cell culture unit.61 S represents drug substrates, M represents drug metabolites, and X represents carbon sources or other soluble components that set cellular function or physiology. 3‐D, three‐dimensional. [Colour figure can be viewed at wileyonlinelibrary.com]