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The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder

Abstract

A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.

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Figure 1: OPN and OCN staining of osteoprogenitors after 21 days of culture.
Figure 2: OPN and OCN staining of MSC cells after 21 days and phase-contrast/bright-field images of alizarin-red-stained cells after 28 days.
Figure 3: Osteogenic oligoarray (macroarray) results for MSCs cultured on planar control, DSQ50 and with DEX for 14 days.
Figure 4: qPCR analysis of selected osetoblastic genes.
Figure 5: IPA for 19,000 gene microarrays.

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Acknowledgements

M.J.D. is a BBSRC David Phillips Fellow, N.G. is an RSE Fellow, R.T. is supported by the BBSRC and ROCO is supported by grants from the BBSRC and EPSRC. We thank A. Curtis for discussions.

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Authors and Affiliations

Authors

Contributions

M.J.D. designed and carried out many of the experiments, analysed most of the data and wrote much of the original manuscript and rewrites. N.G. designed and fabricated the materials and helped with manuscript style/writing and electronics sections. R.T. isolated stem cells, carried out PCR and analysed the PCR data. A.A. carried out the microarray experiments. M.O.R. helped in experimental and material design. P.H. helped M.J.D. with bioinformatics analysis and data presentation. C.D.W. was involved in material design and facilitation of fabrication. R.O.C.O. facilitated stem cell isolation and PCR, helped M.J.D. and R.T. with experimental design and wrote much of the original manuscript and rewrites.

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Correspondence to Matthew J. Dalby.

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Dalby, M., Gadegaard, N., Tare, R. et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nature Mater 6, 997–1003 (2007). https://doi.org/10.1038/nmat2013

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