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Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing
Open accessAbstract
The recent advent of microphysiological systems - microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro - is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-six experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale.
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“OoCs currently constitute the most promising approach to emulate human diseases in vitro55,61.”
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“human-based models have so far been primarily used for toxicity testing61–64, and their application in preclinical and clinical research is still in its infancy.”
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Metadata
- Authors
- Marx, U.
- Corresponding author
- Marx, Uwe
- ORCID
- Marx, Uwe
- Venue
- ALTEX
- Publisher
- ALTEX Edition
- Published
- 2016
- Volume
- 33
- Issue
- 3
- Pages
- 272-321
- ISSN
- 0946-7785 (ISSN-L)
- 1868-596X
- PMC
- PMC5396467
- OpenAlex
- W2373100661
- Cited by
- 295
- References
- 373
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 15 · 2023: 22 · 2022: 17 · 2021: 33 · 2020: 46 · 2019: 48 · 2018: 52 · 2017: 28 · 2016: 9
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- ALTEX (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- KOPS (University of Konstanz) (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion)
- OpenAgrar (submittedVersion, cc-by)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection (cc-by)
- Funders
- National Institutes of Health (Z99 TR999999)
- U.S. Food and Drug Administration
- National Human Genome Research Institute (Z01HG200319)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- microphysiological systems, organ-on-a-chip, toxicity prediction, hazard characterization, alternatives to animal testing, drug development, in vitro disease model, ADME prediction, regulatory acceptance, microfluidics
- MeSH terms
- Animals, Animal Testing Alternatives, Cell Line, Stem Cells, Hazardous Substances, Toxicity Tests, Lab-On-A-Chip Devices
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