Integrating organoids and organ-on-a-chip devices

Organoids and organs-on-chips are two rapidly emerging 3D cell culture techniques that aim to bridge the gap between in vitro 2D cultures and animal models to enable clinically relevant drug discovery and model human diseases. Despite their similar goals, they use different approaches and exhibit varying requirements for implementation. Integrative approaches promise to provide improved cellular fidelity in the format of a device that can control the geometry of the organoid and provide flow, mechanical and electrical stimuli. In this Review, we discuss recent integrative approaches in the areas of intestine, kidney, lung, liver, pancreas, brain, retina, heart and tumour. We start by defining the two fields and describe how they emerged from the fields of tissue engineering, regenerative medicine and stem cells. We compare the scales at which the two methods operate and briefly describe their achievements, followed by studies integrating organoids and organ-on-a-chip devices. Finally, we define implementation limitations and requirements for translation of the integrated devices, including determining the differentiation stage at which an organoid should be placed into an organ-on-a-chip device, providing perfusable vasculature within the organoid and overcoming limitations of cell line and batch-to-batch variability. Organoids and organs-on-chips aim to improve drug testing and disease modelling, but each has limitations. This Review discusses the integration of these systems to improve cellular hierarchy, structural fidelity, reproducibility, throughput, scale-up and efficiency to improve translational outcomes.