Review Article | Published:

Advances in organ-on-a-chip engineering

Nature Reviews Materialsvolume 3pages257278 (2018) | Download Citation

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

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

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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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Affiliations

  1. Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada

    • Boyang Zhang
    • , Anastasia Korolj
    • , Benjamin Fook Lun Lai
    •  & Milica Radisic
  2. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada

    • Anastasia Korolj
    •  & Milica Radisic
  3. Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

    • Milica Radisic
  4. The Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, Ontario, Canada

    • Milica Radisic

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Contributions

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

Competing interests

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

Corresponding author

Correspondence to Milica Radisic.

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DOI

https://doi.org/10.1038/s41578-018-0034-7