Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biomaterials.2011.05.087
Title: Galactosylated cellulosic sponge for multi-well drug safety testing
Authors: Nugraha, B.
Hong, X.
Mo, X.
Tan, L.
Zhang, W. 
Chan, P.-M.
Kang, C.H.
Wang, Y.
Beng, L.T.
Sun, W.
Choudhury, D.
Robens, J.M.
McMillian, M.
Silva, J.
Dallas, S.
Tan, C.-H. 
Yue, Z.
Yu, H. 
Keywords: Cellulose
Cytochrome P450
Drug induction
Galactose
Hydrogel
Sponge
Issue Date: Oct-2011
Citation: Nugraha, B., Hong, X., Mo, X., Tan, L., Zhang, W., Chan, P.-M., Kang, C.H., Wang, Y., Beng, L.T., Sun, W., Choudhury, D., Robens, J.M., McMillian, M., Silva, J., Dallas, S., Tan, C.-H., Yue, Z., Yu, H. (2011-10). Galactosylated cellulosic sponge for multi-well drug safety testing. Biomaterials 32 (29) : 6982-6994. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2011.05.087
Abstract: Hepatocyte spheroids can maintain mature differentiated functions, but collide to form bulkier structures when in extended culture. When the spheroid diameter exceeds 200 μm, cells in the inner core experience hypoxia and limited access to nutrients and drugs. Here we report the development of a thin galactosylated cellulosic sponge to culture hepatocytes in multi-well plates as 3D spheroids, and constrain them within a macroporous scaffold network to maintain spheroid size and prevent detachment. The hydrogel-based soft sponge conjugated with galactose provided suitable mechanical and chemical cues to support rapid formation of hepatocyte spheroids with a mature hepatocyte phenotype. The spheroids tethered in the sponge showed excellent maintenance of 3D cell morphology, cell-cell interaction, polarity, metabolic and transporter function and/or expression. For example, cytochrome P450 (CYP1A2, CYP2B2 and CYP3A2) activities were significantly elevated in spheroids exposed to β-naphthoflavone, phenobarbital, or pregnenolone-16α-carbonitrile, respectively. The sponge also exhibits minimal drug absorption compared to other commercially available scaffolds. As the cell seeding and culture protocols are similar to various high-throughput 2D cell-based assays, this platform is readily scalable and provides an alternative to current hepatocyte platforms used in drug safety testing applications. © 2011 Elsevier Ltd.
Source Title: Biomaterials
URI: http://scholarbank.nus.edu.sg/handle/10635/76237
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2011.05.087
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