title: Fabrication of 3D-culture platform with sandwich architecture for preserving liver-specific functions of hepatocytes using 3D bioprinter.
abstract: The development of new three-dimensional (3D) cell culture system that maintains the physiologically relevant signals of hepatocytes is essential in drug discovery and tissue engineering research. Conventional two-dimensional (2D) culture yields cell growth, proliferation, and differentiation. However, gene expression and signaling profiles can be different from in vivo environment. Here, we report the fabrication of a 3D culture system using an artificial scaffold and our custom-made inkjet 3D bioprinter as a new strategy for studying liver-specific functions of hepatocytes. We built a 3D culture platform for hepatocytes-attachment and formation of cell monolayer by interacting the galactose chain of galactosylated alginate gel (GA-gel) with asialoglycoprotein receptor (ASGPR) of hepatocytes. The 3D geometrical arrangement of cells was controlled by using 3D bioprinter, and cell polarity was controlled with the galactosylated hydrogels. The fabricated GA-gel was able to successfully promote adhesion of hepatocytes. To observe liver-specific functions and to mimic hepatic cord, an additional parallel layer of hepatocytes was generated using two gel sheets. These results indicated that GA-gel biomimetic matrices can be used as a 3D culture system that could be effective for the engineering of liver tissues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1583-1592, 2017.
authors.affiliation: Division of Innovative Life Sciences, Graduate School of Innovative Life Science, University of Toyama, Japan.|Department of Regenerative Medicine and Biomedical Engineering, Saga University, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Arai
authors.affiliation: Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Motonori
authors.initials: M
authors.lastname: Okabe
authors.affiliation: Biomaterials Center for Regenerative Medical Engineering, Foundation for Advancement of International Science, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Goto
authors.affiliation: Division of Biomedical System Engineering, Graduate School of Science and Engineering for Education, University of Toyama, Toyama, Japan.
authors.forename: Tanveer Ahmad
authors.initials: TA
authors.lastname: Mir
authors.affiliation: Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Soko
authors.affiliation: Division of Biomedical System Engineering, Graduate School of Science and Engineering for Education, University of Toyama, Toyama, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Tsukamoto
authors.affiliation: Biomaterials Center for Regenerative Medical Engineering, Foundation for Advancement of International Science, Japan.|Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akaike
authors.affiliation: Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nikaido
authors.affiliation: Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Kaixuan
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Division of Biomedical System Engineering, Graduate School of Science and Engineering for Education, University of Toyama, Toyama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D004867:Equipment Design; D005690:Galactose / Q000031:analogs & derivatives / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D008813:Mice, Inbred ICR; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000295:instrumentation*
chemical_list: D000464:Alginates; D037263:Asialoglycoprotein Receptor; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D005690:Galactose
keywords: 3D bioprinter; 3D culture; galactosylated alginate (GA-gel); hepatocyte; tissue engineering