Microfluidic Platform with Local Oxygen Sensors Demonstrates That 3D Blood Vessel Networks Exhibit Time‐Dependent Changes in Oxygen Concentrations During Their Formation and Perfusion

Abstract Organ‐on‐chip (OoC) technology is rapidly advancing, with in vitro human models becoming increasingly popular for their ability to mimic the smallest functional units of human organs using human‐derived cells integrated into microfluidic systems. These models can offer significant advantages over animal models in pharmacology, biomedical science, and toxicology, prompting a drive for more physiologically accurate models that better replicate human tissue complexity. However, the development of these models faces significant challenges, particularly in supplying adequate nutrients and oxygen to cells within 3D constructs, where diffusion limitations and the use of low‐gas‐permeable materials can lead to suboptimal culture conditions. To address these challenges, integrating functional vascular networks into OoC models has become a focal point of research, though the impact on local oxygen levels remains inadequately understood. This study introduces a microfluidic platform with integrated optical oxygen sensors, enabling continuous monitoring of oxygen levels during the formation of human induced pluripotent stem cells (hiPSC)‐derived vascular networks. Despite establishing functional vasculature, oxygen levels fluctuated and decreased over time, highlighting the limitations of current perfusion methods. The findings emphasize the need for improved oxygenation strategies and the importance of continuous oxygen monitoring for the development of robust and physiologically relevant OoC systems.