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.