Using physiologically-based pharmacokinetic-guided "body-on-a-chip" systems to predict mammalian response to drug and chemical exposure

    Authors

    J. H. Sung; B. Srinivasan; M. B. Esch; W. T. McLamb; C. Bernabini; M. L. Shuler;J. J. Hickman

    Comments

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    Abbreviated Journal Title

    Exp. Biol. Med.

    Keywords

    Microphysiological system; PBPK models; microfabrication; chemical; analysis; electrical analysis; mechanical analysis; CELL-CULTURE ANALOG; NEUROMUSCULAR-JUNCTION FORMATION; FLUORESCENCE; OPTICAL-DETECTION; SINGLE CARDIAC MYOCYTES; SKELETAL-MUSCLE TISSUE; BREAST-CANCER CELLS; DEFINED SYSTEM; MICROELECTRODE ARRAYS; MICROFLUIDIC; PLATFORM; BARRIER FUNCTION; Medicine, Research & Experimental

    Abstract

    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.

    Journal Title

    Experimental Biology and Medicine

    Volume

    239

    Issue/Number

    9

    Publication Date

    1-1-2014

    Document Type

    Review

    Language

    English

    First Page

    1225

    Last Page

    1239

    WOS Identifier

    WOS:000342773100014

    ISSN

    1535-3702

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