Advances in human organoids-on-chips in biomedical research

Abstract

Organoids-on-chips is opening up new frontier of research in biomedical field by combining organoids and organs-on-chips technology. The integrative technology offers great opportunities to maximize the potentials of organoids with higher fidelity, thus building advanced organ model systems in a physiologically relevant manner. In this review, we highlight the key features of organoids-on-chips and how this integrative technology could be used to build organoids in higher fidelity under controlled cellular microenvironment. We then introduce the recent progress of organoids-on-chips and their applications in biomedical research. We also discuss the opportunities and challenges of the nascent field of organoids-on-chips that lie ahead to accelerate their utility in disease research, drug testing, and regenerative medicine.

Keywords: biomedical research; organoid; organoids-on-chips; organs-on-chips; stem cell.

Figure 1.

Schematic of engineered organoids-on-chips by combining organs-on-chips (organ chips) and organoids. Organoids are 3D multicellular tissues that derived from human PSCs (ESCs and iPSCs) or ASCs by self-organization. Organ chips can be utilized for engineering organoids by guiding stem cells differentiation, organization, and organoids formation in a controlled microenvironment, thereby improving functions and maturity of organoids for advancing biomedical research.

Figure 2.

Illustration of integrative strategies to engineer advanced organoids-on-chips. The perfused 3D culture on chip may facilitate nutrient exchange and long-term survival of organoids. The spatiotemporal control of the biochemical components including growth factors gradients may guide organoid formation resembled in vivo. The spatiotemporal control over the biophysical microenvironment cues, such as stretch, topological structure, and substrate stiffness may steer organoid differentiation and formation during development. The incorporation of pre-vascular networks on chip may facilitate the vascularization of organoids. Organ chips with compartmentalized microenvironments may allow co-culture of different types of organoids, recapitulating the complex interactions in organism.

Figure 3.

Representative types and functions of organoids-on-chips. (A) A perfusable organ chip was fabricated for in situ differentiation and formation of brain organoids from hiPSCs, and this brain organoid-on-a-chip was used to model prenatal nicotine exposure. Reproduced with permission [20]. Copyright 2018, Royal Society of Chemistry. (B) A perfusable liver organoids-on-a-chip derived from hiPSCs were developed for drug testing. Reproduced with permission [44]. Copyright 2018, Royal Society of Chemistry. (C) Human intestinal organoids-derived epithelial cells were incorporated into microengineered chips under continuous media flow, which generated polarized intestinal folds that contained multiple epithelial subtypes and were biologically responsive to exogenous stimuli. Reproduced with permission [42]. Copyright 2018, Elsevier. (D) A perfused multi-organoid system contained two compartmentalized regions enabled the co-culture of liver and islet organoids from hiPSCs, which could recapitulate human-relevant liver-islet axis in normal and Type 2 diabetes states. Reproduced with permission [87]. Copyright 2022, Wiley.

Figure 4.

Schematic depiction of advanced organoids-on-chips to meet the needs of biomedical research, extending their applications in organ developmental studies, disease modeling, translational research, and personalized medicine.