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Advances in organ-on-a-chip engineering

Abstract

Predicting the effects of drugs before human clinical trials is at the heart of drug screening and discovery processes. The cost of drug discovery is steadily increasing owing to the limited predictability of 2D cell culture and animal models. The convergence of microfabrication and tissue engineering gave rise to organ-on-a-chip technologies, which offer an alternative to conventional preclinical models for drug screening. Organ-on-a-chip devices can replicate key aspects of human physiology crucial for the understanding of drug effects, improving preclinical safety and efficacy testing. In this Review, we discuss how organ-on-a-chip technologies can recreate functions of organs, focusing on tissue barrier properties, parenchymal tissue function and multi-organ interactions, which are three key aspects of human physiology. Specific organ-on-a-chip systems are examined in terms of cell sources, functional hallmarks and available disease models. Finally, we highlight the challenges that need to be overcome for the clinical translation of organ-on-a-chip devices regarding materials, cellular fidelity, multiplexing, sensing, scalability and validation.

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Fig. 1: Major milestones in organ-on-a-chip technology and establishment of organ-on-a-chip companies.
Fig. 2: Reproducing tissue barrier function.
Fig. 3: Reproducing elongated parenchymal tissues.
Fig. 4: Reproducing spherical parenchymal tissues.
Fig. 5: Body-on-a-chip devices.
Fig. 6: Functional scaling of body-on-a-chip devices.
Fig. 7: Modelling multi-organ interactions.

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Acknowledgements

The authors thank M. Lecce and L. D. Huyer for helping with the editing of this manuscript. This work was made possible by the National Sciences and Engineering Research Council of Canada (NSERC) Postgraduate Scholarships-Doctoral Program awarded to B.F.L.L., Alexander Graham Bell Canada Graduate Scholarships-Doctoral Program awarded to A.K. and the Canadian Institutes of Health Research (CIHR) Banting Postdoctoral Fellowship to B.Z. This work was also funded by the CIHR Operating Grants (MOP-126027 and MOP-137107), NSERC Discovery Grant (RGPIN-2015-05952), NSERC Steacie Fellowship (SMFSU 4620), Heart and Stroke Foundation Grant-in-Aid (G-16-00012), NSERC-CIHR Collaborative Health Research Grant (CHRPJ 4937) and NSERC Strategic Grant (STPGP 5066) to M.R.

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B.Z., A.K. and B.F.L.L. wrote and edited the manuscript. M.R. supervised the work and edited the manuscript.

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Correspondence to Milica Radisic.

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B.Z. and M.R. hold equity in TARA Biosystems Inc.

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American Institute for Medical and Biological Engineering (AIMBE): http://aimbe.org

Comprehensive In Vitro Proarrhythmia Assay (CiPA): http://cipaproject.org

IQ Consortium: https://iqconsortium.org

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Zhang, B., Korolj, A., Lai, B.F.L. et al. Advances in organ-on-a-chip engineering. Nat Rev Mater 3, 257–278 (2018). https://doi.org/10.1038/s41578-018-0034-7

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