Organoids meet microfluidics: recent advancements, challenges, and future of organoids-on-chip.

Organoids are three-dimensional, miniaturized tissue-like structures derived from either stem cells or primary cells, emerging as powerful in vitro models for studying developmental biology, disease pathology, and drug discovery. These organoids more accurately mimic cell-cell interactions and complexities of human tissues compared to traditional cell cultures. However, challenges such as limited nutrient supply and biomechanical cue replication hinder their maturation and viability. Microfluidic technologies, with their ability to control fluid flow and mimic the mechanical environment of tissues, have been integrated with organoids to create organoid-on-chip models that address these limitations. These models not only improve the physiological relevance of organoids but also enable more precise investigation of disease mechanisms and therapeutic responses. By combining microfluidics and organoids, several advanced organoids-on-chip models have been developed to investigate mechanical and biochemical cues involved in disease progression. This review discusses various methods to develop organoids-on-chip and the recently established organoids-on-chip models with their advanced functions. Finally, we highlighted potential strategies to enhance the functionality of organoid models, aiming to overcome current limitations and bridge the gap between current cell culture models and clinical applications, advancing personalized medicine, and improving therapeutic testing.