Multi-organ-on-a-chip: Modeling strategy, method, and biomedical applications

In recent years, organ-on-a-chip technology has developed rapidly in the biomedical field. Traditional single-organ chip provides a reliable experimental platform for disease modeling and drug development by simulating the physiological function of a specific organ, and some data generated by these platforms have been recognized by the Food and Drug Administration. Nevertheless, single-organ chip cannot fully simulate the complex interactions between body organs. To address these limitations, multi-organ-on-a-chip (MOOC) platform emerged. By using microelectromechanical system technology and 3D printing method, MOOC can integrate multiple organs with different structures/connections and precisely regulate the parameters of a micro-environment, such as fluid dynamics, chemical gradient, and mechanical stress. Moreover, the use of a biocompatible membrane and matrix gel materials enables the three-dimensional construction of cellular microenvironments, which enhance substance exchange and signal transmission between organs. Combined with a real-time monitoring system, the MOOC platform offers dynamic feedback and regulatory capabilities to simulate the complex interactions of human physiology more accurately. This paper recently reviews research progress in MOOC design strategies, construction methods, and their applications in drug discovery, disease research, and personalized medicine. Additionally, the technical challenges of MOOC technology and outlook of MOOC development trend are also included in this paper. In summary, MOOC technology represents an emerging platform with significant potential to improve disease modeling and early stage drug development. Furthermore, its integration with other frontier technologies may offer new opportunities to study disease mechanisms and explore novel therapeutic strategies.