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Dynamic three-dimensional micropatterned cell co-cultures within photocurable and chemically degradable hydrogels

Authors

  • Shinji Sugiura,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA
    2. Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
    3. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan
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  • Jae Min Cha,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA
    2. Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
    3. Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co., Ltd., Seoul, South Korea
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  • Fumiki Yanagawa,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA
    2. Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • Pinar Zorlutuna,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA
    2. Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
    3. Biomedical Engineering Program and Mechanical Engineering Department, University of Connecticut, Storrs, CT, USA
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  • Hojae Bae,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA
    2. Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
    3. College of Animal Bioscience and Technology, Department of Bioindustrial Technologies, Konkuk University, Seoul, South Korea
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  • Ali Khademhosseini

    Corresponding author
    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA
    2. Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
    3. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA
    • Correspondence to: Ali Khademhosseini, Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. E-mail: alik@rics.bwh.harvard.edu

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Abstract

In this paper we report on the development of dynamically controlled three-dimensional (3D) micropatterned cellular co-cultures within photocurable and chemically degradable hydrogels. Specifically, we generated dynamic co-cultures of micropatterned murine embryonic stem (mES) cells with human hepatocellular carcinoma (HepG2) cells within 3D hydrogels. HepG2 cells were used due to their ability to direct the differentiation of mES cells through secreted paracrine factors. To generate dynamic co-cultures, mES cells were first encapsulated within micropatterned photocurable poly(ethylene glycol) (PEG) hydrogels. These micropatterned cell-laden PEG hydrogels were subsequently surrounded by calcium alginate (Ca-Alg) hydrogels containing HepG2 cells. After 4 days, the co-culture step was halted by exposing the system to sodium citrate solution, which removed the alginate gels and the encapsulated HepG2 cells. The encapsulated mES cells were then maintained in the resulting cultures for 16 days and cardiac differentiation was analysed. We observed that the mES cells that were exposed to HepG2 cells in the co-cultures generated cells with higher expression of cardiac genes and proteins, as well as increased spontaneous beating. Due to its ability to control the 3D microenvironment of cells in a spatially and temporally regulated manner, the method presented in this study is useful for a range of cell-culture applications related to tissue engineering and regenerative medicine. Copyright © 2013 John Wiley & Sons, Ltd.

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