Liver-on-a-Chip: Searching for a Balance Between Biomimetics and Functionality

One of the common issues in the R&D of new drugs is the failure of clinical trials caused by the species-specific inadequacy of animal models to assess drugs' efficiency and safety. Therefore, systems like organ-on-a-chip and, particularly, liver-on-a-chip (LOC) can be an efficient tool for recapitulating in vivo-like human physiology at the microscale. This review focuses on discussing LOC design, emphasizing its architecture and validation to reveal the trends in searching for a balance between biomimetics and functionality. We found that the huge variety of already published models can be divided into five groups based on their configuration complexity: flat one-channel, flat two-channel, vertically stacked multilayered, hexagonal-patterned, and multi-well chips. While researchers attempt to recapitulate the liver's histology and its functions in detail by increasing the complexity of devices' architectonics, industrial companies prefer to promote more simple and flexible solutions. Thus, the LOC designs of the future require neglecting some liver characteristics to make them standardizable and sustainable, which could facilitate their introduction into the market and clinics.