A comprehensive review on organ-on-chips as powerful preclinical models to study tissue barriers.

In the preclinical stage of drug development, 2D and 3D cell cultures under static conditions followed by animal models are utilized. However, these models are insufficient to recapitulate the complexity of human physiology. With the developing organ-on-chip (OoC) technology in recent years, human physiology and pathophysiology can be modeled better than traditional models. In this review, the need for OoC platforms is discussed and evaluated from both biological and engineering perspectives. The cellular and extracellular matrix components are discussed from a biological perspective, whereas the technical aspects such as the intricate working principles of these systems, the pivotal role played by flow dynamics and sensor integration within OoCs are elucidated from an engineering perspective. Combining these two perspectives, bioengineering applications are critically discussed with a focus on tissue barriers such as blood-brain barrier, ocular barrier, nasal barrier, pulmonary barrier and gastrointestinal barrier, featuring recent examples from the literature. Furthermore, this review offers insights into the practical utility of OoC platforms for modeling tissue barriers, showcasing their potential and drawbacks while providing future projections for innovative technologies.