Journal
EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 239, Issue 9, Pages 1225-1239Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370214529397
Keywords
Microphysiological system; PBPK models; microfabrication; chemical analysis; electrical analysis; mechanical analysis
Categories
Funding
- National Research Foundation of Korea (NRF) [2011-0013862]
- KFRI (Korea Food Research Institute) [E0121705]
- Hongik University Research Fund
- NSF [CBET-1106153]
- National Center For Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) Microphysiological Systems [UH2TR000516-02SI]
- NCATS NIH Microphysiological Systems [UH2TR000516]
- NINDS [R01NS050452]
- NIBIB [R01EB009429]
- National Research Foundation of Korea [2011-0013862] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The continued development of invitro systems that accurately emulate human response to drugs or chemical agents will impact drug development, our understanding of chemical toxicity, and enhance our ability to respond to threats from chemical or biological agents. A promising technology is to build microscale replicas of humans that capture essential elements of physiology, pharmacology, and/or toxicology (microphysiological systems). Here, we review progress on systems for microscale models of mammalian systems that include two or more integrated cellular components. These systems are described as a body-on-a-chip, and utilize the concept of physiologically-based pharmacokinetic (PBPK) modeling in the design. These microscale systems can also be used as model systems to predict whole-body responses to drugs as well as study the mechanism of action of drugs using PBPK analysis. In this review, we provide examples of various approaches to construct such systems with a focus on their physiological usefulness and various approaches to measure responses (e.g. chemical, electrical, or mechanical force and cellular viability and morphology). While the goal is to predict human response, other mammalian cell types can be utilized with the same principle to predict animal response. These systems will be evaluated on their potential to be physiologically accurate, to provide effective and efficient platform for analytics with accessibility to a wide range of users, for ease of incorporation of analytics, functional for weeks to months, and the ability to replicate previously observed human responses.
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