title: Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution ofin-vitroliver technologies.
abstract: The liver performs many key functions, the most prominent of which is serving as the metabolic hub of the body. For this reason, the liver is the focal point of many investigations aimed at understanding an organism's toxicological response to endogenous and exogenous challenges. Because so many drug failures have involved direct liver toxicity or other organ toxicity from liver generated metabolites, the pharmaceutical industry has constantly sought superior, predictivein-vitromodels that can more quickly and efficiently identify problematic drug candidates before they incur major development costs, and certainly before they are released to the public. In this broad review, we present a survey and critical comparison ofin-vitroliver technologies along a broad spectrum, but focus on the current renewed push to develop "organs-on-a-chip". One prominent set of conclusions from this review is that while a large body of recent work has steered the field towards an ever more comprehensive understanding of what is needed, the field remains in great need of several key advances, including establishment of standard characterization methods, enhanced technologies that mimic thein-vivocellular environment, and better computational approaches to bridge the gap between thein-vitroandin-vivoresults.
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA.
authors.forename: O B
authors.initials: OB
authors.lastname: Usta
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: McCarty
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bale
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hegde
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA.
authors.forename: R
authors.initials: R
authors.lastname: Jindal
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bhushan
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA.
authors.forename: I
authors.initials: I
authors.lastname: Golberg
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, MA 02114, USA ; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd., Piscataway, NJ 08854, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Yarmush