title: Using physiologically-based pharmacokinetic-guided "body-on-a-chip" systems to predict mammalian response to drug and chemical exposure.
abstract: The continued development of in vitro 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.
authors.affiliation: Chemical Engineering, Hongik University, Seoul 121-791, Republic of Korea.
authors.forename: Jong Hwan
authors.initials: JH
authors.lastname: Sung
authors.affiliation: NanoScience Technology Center, University of Central Florida, Orlando, FL 32826, USA.
authors.forename: Balaji
authors.initials: B
authors.lastname: Srinivasan
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Mandy Brigitte
authors.initials: MB
authors.lastname: Esch
authors.affiliation: NanoScience Technology Center, University of Central Florida, Orlando, FL 32826, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: McLamb
authors.affiliation: NanoScience Technology Center, University of Central Florida, Orlando, FL 32826, USA.
authors.forename: Catia
authors.initials: C
authors.lastname: Bernabini
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA jhickman@mail.ucf.edu mls50@cornell.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shuler
authors.affiliation: NanoScience Technology Center, University of Central Florida, Orlando, FL 32826, USA Biomolecular Science Center, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USA jhickman@mail.ucf.edu mls50@cornell.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hickman
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008954:Models, Biological; D010599:Pharmacokinetics; D046509:Tissue Culture Techniques / Q000295:instrumentation / Q000379:methods
keywords: Microphysiological system; PBPK models; chemical analysis; electrical analysis; mechanical analysis; microfabrication