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Two‐Dimensional Multiarray Formation of Hepatocyte Spheroids on a Microfabricated PEG‐Brush Surface
Author(s) -
Otsuka Hidenori,
Hirano Akihiro,
Nagasaki Yukio,
Okano Teruo,
Horiike Yasuhiro,
Kataoka Kazunori
Publication year - 2004
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200300822
Subject(s) - spheroid , hepatocyte , ethylene glycol , chemistry , peg ratio , biophysics , substrate (aquarium) , albumin , cell , biosensor , nanotechnology , biochemistry , materials science , biology , in vitro , ecology , organic chemistry , finance , economics
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.