Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor

Tsimbouri, Penelope M. and Childs, Peter G. and Pemberton, Gabriel D. and Yang, Jingli and Jayawarna, Vineetha and Orapiriyakul, Wich and Burgess, Karl and González-García, Cristina and Blackburn, Gavin and Thomas, Dilip and Vallejo-Giraldo, Catalina and Biggs, Manus J. P and Curtis, Adam S. G. and Salmerón-Sánchez, Manuel and Reid, Stuart and Dalby, Matthew J. (2017) Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor. Nature Biomedical Engineering, 1 (9). pp. 758-770. ISSN 2157-846X

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    Abstract

    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.