title: Bioreactor technologies to support liver function in vitro.
abstract: Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drives efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Ebrahimkhani
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jaclyn A Shepard
authors.initials: JA
authors.lastname: Neiman
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Micha Sam B
authors.initials: MS
authors.lastname: Raredon
authors.affiliation: CN Bio Innovations Ltd, Oxford, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hughes
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Gynepathology Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: griff@mit.edu.
authors.forename: Linda G
authors.initials: LG
authors.lastname: Griffith
mesh_terms: D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods* / Q000639:trends; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000502:physiology*; D009924:Organ Culture Techniques / Q000379:methods / Q000639:trends
keywords: Bioreactor; Drug development; Drug toxicity; Hepatocytes; Liver non-parenchymal cells; Microfluidic; Organ on chip; Tissue engineering