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A thixotropic nanocomposite gel for three-dimensional cell culture

Nature Nanotechnology volume 3, pages 671–675 (2008)Cite this article

Abstract

Thixotropic materials, which become less viscous under stress and return to their original state when stress is removed1, have been used to deliver gel–cell constructs2 and therapeutic agents3. Here we show that a polymer–silica nanocomposite thixotropic gel can be used as a three-dimensional cell culture material. The gel liquefies when vortexed—allowing cells and biological components to be added—and resolidifies to trap the components when the shear force from spinning is removed. Good permeability of nutrients and gases through the gel allows various cell types to proliferate and be viable for up to three weeks. Human mesenchymal stem cells cultured in stiffer gels developed bone-like behaviour, showing that the rheological properties of the gel can control cell differentiation. No enzymatic4, chemical5,6, or photo-crosslinking7,8,9, changes in ionic strength10,11,12,13,14 or temperature15,16 are required to form or liquefy the gel, offering a way to sub-culture cells without using trypsin—a protease commonly used in traditional cell culture techniques.

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Figure 1: Synthesis and properties of PEG–silica gels.
Figure 2: Rheological characteristics of PEG–silica gels.
Figure 3: Viability of cells cultured in 3D PEG–silica gels.
Figure 4: Using PEG–silica gels for 3D cell culture.

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Acknowledgements

The authors thank Yuangang Zheng, Fan Lee, Bao Guo Hsieh, Karthikeyan Narayanan, Soon Huat Low, Xingfang Su, Su Seong Lee, Yu Han, Kwong Joo Leck and Benjamin Tai for helpful discussions. The HSC-T6 cells used in this study were a generous gift from S. Friedman (Mount Sinai School of Medicine, New York). This work was supported by the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore).

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  1. Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore

    Y. Shona Pek, Andrew C. A. Wan, Asha Shekaran, Lang Zhuo & Jackie Y. Ying

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  1. Y. Shona Pek
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  2. Andrew C. A. Wan
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  3. Asha Shekaran
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Contributions

J.Y.Y., A.C.A.W. and Y.S.P. led the project, conducted the data analysis and wrote the paper. Y.S.P., A.C.A.W. and A.S. performed the experiments and collected the data. L.Z. provided cells and discussions for some of the cell culture studies.

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Correspondence to Andrew C. A. Wan or Jackie Y. Ying.

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Pek, Y., Wan, A., Shekaran, A. et al. A thixotropic nanocomposite gel for three-dimensional cell culture. Nature Nanotech 3, 671–675 (2008). https://doi.org/10.1038/nnano.2008.270

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