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Citation
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HERO ID
784767
Reference Type
Journal Article
Title
Galactosylated cellulosic sponge for multi-well drug safety testing
Author(s)
Nugraha, B; Hong, X; Mo, X; Tan, L; Zhang, W; Chan, PM; Kang, CH; Wang, Y; Beng, LT; Sun, W; Choudhury, D; Robens, JM; McMillian, M; Silva, J; Dallas, S; Tan, CH; Yue, Z; Yu, H
Year
2011
Is Peer Reviewed?
Yes
Journal
Biomaterials
ISSN:
0142-9612
EISSN:
1878-5905
Volume
32
Issue
29
Page Numbers
6982-6994
Language
English
PMID
21741702
DOI
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.
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Dioxin (2012 Project Page for Final Report)
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