Bone grafts are one of the most commonly transplanted tissues. However, autologous grafts are in short supply, and can be associated with pain and donor-site morbidity. The creation of tissue-engineered bone grafts could help to fulfil clinical demand and provide a crucial resource for drug screening. Here, we show that vibrations of nanoscale amplitude provided by a newly developed bioreactor can differentiate a potential autologous cell source, mesenchymal stem cells (MSCs), into mineralized tissue in 3D. We demonstrate that nanoscale mechanotransduction can stimulate osteogenesis independently of other environmental factors, such as matrix rigidity. We show this by generating mineralized matrix from MSCs seeded in collagen gels with stiffness an order of magnitude below the stiffness of gels needed to induce bone formation in vitro. Our approach is scalable and can be compatible with 3D scaffolds.
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This work was supported by grants to S.R. and M.J.D. from the BBSRC, BBSRC/SFI and EPSRC (BB/N012690/1, BB/P00220X/1, EP/N013905/1, EP/N012631/1 and EP/P001114/1), along with a Wolfson Merit Award from The Royal Society and a programme grant from Find a Better Way. M.J.P.B. is funded by SFI grant nos. 11/SIRG/B2135 and 13/RC/2073. P.G.C. was funded by an STFC/BBSRC fellowship. We thank J. Hough, H. Nikukar, I. Tifenbrun and K. Robertson for their discussion, C.-A. Smith for technical support, and E. Manson for help with metabolite analysis. We also thank C. Boyle, S. Robertson and P. Campsie for help with the construction of the bioreactor.
The authors declare no competing financial interests.
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Tsimbouri, P.M., Childs, P.G., Pemberton, G.D. et al. Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor. Nat Biomed Eng 1, 758–770 (2017). https://doi.org/10.1038/s41551-017-0127-4
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