Two-Dimensional Multiarray Formation of Hepatocyte Spheroids on a Microfabricated PEG-Brush Surface

Authors

  • Hidenori Otsuka Dr.,

    1. Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8656, Japan, Fax: (+81) 3-5841-7139
    2. Present address: Biomaterials Center, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
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  • Akihiro Hirano,

    1. Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8656, Japan, Fax: (+81) 3-5841-7139
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  • Yukio Nagasaki Dr.,

    1. Department of Materials Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan
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  • Teruo Okano Dr.,

    1. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan
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  • Yasuhiro Horiike Dr.,

    1. Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8656, Japan, Fax: (+81) 3-5841-7139
    2. Present address: Biomaterials Center, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
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  • Kazunori Kataoka Dr.

    1. Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8656, Japan, Fax: (+81) 3-5841-7139
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Abstract

A two-dimensional microarray of ten thousand (100×100) hepatocyte heterospheroids, underlaid with endothelial cells, was successfully constructed with 100 μm spacing in an active area of 20×20 mm on microfabricated glass substrates that were coated with poly(ethylene glycol) brushes. Cocultivation of hepatocytes with endothelial cells was essential to stabilize hepatocyte viability and liver-specific functions, allowing us to obtain hepatocyte spheroids with a diameter of 100 μm, functioning as a miniaturized liver to secret albumin for at least one month. The most important feature of this study is that these substrates are defined to provide an unprecedented control of substrate properties for modulating cell behavior, employing both surface engineering and synthetic polymer chemistry. The spheroid array constructed here is highly useful as a platform of tissue and cell-based biosensors and detects a wide variety of clinically, pharmacologically, and toxicologically active compounds through a cellular physiological response.

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