Recent advances and challenges in organoid-on-a-chip technology

Conventional 2-dimensional cell culture poorly mimics human-relevant models, which is considered a major challenge in biological research. Organoids are a recent breakthrough in 3-dimensional (3D) in vitro tissue engineering that better reflect the physiological, morphological, and functional properties of in vivo organs (e.g., brain, heart, kidney, lung, and liver). Consequently, organoids are extensively used in various impactful biomedical applications including organ development, disease modeling, and clinical drug testing. However, organoid technology still has several limitations, including low reproducibility, vascularization, limited nutrient uptake and distribution (affecting the level of organoid maturation), lack of standardization, and intra-clonal variability. Efforts have been made to overcome these shortcomings of organoid culture. Microfluidic technology has successfully facilitated the establishment of organoid-on-a-chip systems, which effectively improve the structural and physiological features of organoids in a controlled manner. This review discusses the recent advances and developments in organoid-on-a-chip technology. We hope that this study will motivate researchers to explore the possible engagement between microfluidic devices and self-assembled 3D cell cultures to leverage the enhanced quality of organoids, which will have favorable impacts on future tissue regeneration and regenerative therapies.