Organs-on-chips at the frontiers of drug discovery
Open accessAbstract
Improving the effectiveness of preclinical predictions of human drug responses is critical to reducing costly failures in clinical trials. Recent advances in cell biology, microfabrication and microfluidics have enabled the development of microengineered models of the functional units of human organs - known as organs-on-chips - that could provide the basis for preclinical assays with greater predictive power. Here, we examine the new opportunities for the application of organ-on-chip technologies in a range of areas in preclinical drug discovery, such as target identification and validation, target-based screening, and phenotypic screening. We also discuss emerging drug discovery opportunities enabled by organs-on-chips, as well as important challenges in realizing the full potential of this technology.
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Organ-on-chip systems have shown promise sustaining functional microtissues for relatively extended timeframes.
“Recently, organ-on-chip systems—microphysiological systems that combine the use of microfluidics, tissue engineering, and microfabrication tools—have shown promise sustaining functional microtissues for relatively extended timeframes [9,10,11,12].”
From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [10]
The ‘Comparison with conventional models’ section says organs-on-chips can reconstitute organ-level physiological functions, supporting the functional-microtissue part of the claim. But the passages do not establish that this function is sustained for relatively extended periods; ‘Current challenges and limitations’ instead describes long-term culture as a major challenge. Page numbers are not available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe lung-on-a-chip system was also used as a model for lung diseases such as pulmonary edema.
“C: the system was also used as a model for lung diseases like pulmonary edema.”
From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [33]
A lung-on-a-chip system was able to recreate organ-level functions, including an inflammatory response to bacteria.
“B: the system could recreate organ-level functions, such as an inflammatory response bacteria.”
From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [33]
3D tissue models, such as in vitro tissue-engineered disease models, have shown promise for overcoming obstacles faced with 2D cultured cells and animal models.
“3D tissue models, such as in vitro tissue-engineered disease models have shown promise for addressing the current obstacles faced with 2D in vitro cultured cells and animal models [352–356].”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [352]
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- Authors
- Esch, E. W., Bahinski, A., & Huh, D.
- Affiliations
- University of Pennsylvania (US)
- Harvard University (US)
- Corresponding author
- Huh, Dongeun
- Venue
- Nature Reviews Drug Discovery
- Published
- 2015-03-20
- Volume
- 14
- Issue
- 4
- Pages
- 248-260
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- PMC
- PMC4826389
- OpenAlex
- W2010546163
- Cited by
- 1,185
- References
- 104
- Citations by year
- 2026: 57 · 2025: 88 · 2024: 74 · 2023: 87 · 2022: 107 · 2021: 124 · 2020: 114 · 2019: 133 · 2018: 134 · 2017: 151 · 2016: 94 · 2015: 19 · 2014: 1 · 2012: 1
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (DP2HL127720)
- National Institute of Environmental Health Sciences (P30ES013508)
- National Center for Chronic Disease Prevention and Health Promotion (1DP2HL127720-01)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- organ-on-a-chip, drug discovery, preclinical drug screening, toxicity screening, target identification and validation, target-based screening, phenotypic screening, microfluidics, microfabrication, stratified medicine, predictive preclinical models
- MeSH terms
- Animals, Computer Simulation, Drug Industry, Drug Evaluation, Preclinical, Humans, Models, Biological, Pharmacokinetics, Rare Diseases, Drug Discovery, High-Throughput Screening Assays
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