An Experimental and Computational Investigation of Bone Formation in Mechanically Loaded Trabecular Bone Explants
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Understanding how bone marrow multipotent stromal cells (MSCs) contribute to new bone formation and remodeling in vivo is of principal importance for informing the development of effective bone tissue engineering strategies in vitro. However, the precise in situ stimuli that MSCs experience have not been fully established. The shear stress generated within the bone marrow of physiologically loaded samples has never been determined, but could be playing an important role in the generation of sufficient stimulus for MSCs to undergo osteogenic differentiation. In this study fluid structure interaction (FSI) computational models were used in conjunction with a bioreactor which physiologically compresses explanted trabecular bone samples to determine whether MSCs can be directly stimulated by mechanical cues within the bone marrow. Experimentally loaded samples were found to have greater osteogenic activity, as verified by bone histomorphometry, compared to control static samples. FSI models demonstrated a linear relationship between increasing shear stress and decreasing bone volume. The FSI models demonstrated that bone strain, not marrow shear stress, was likely the overall driving mechanical signal for new bone formation during compression. However, the shear stress generated in the models is within the range of values which has been shown previously to generate an osteogenic response in MSCs.
KeywordsBone marrow multipotent stromal cells Bone tissue engineering Bone marrow Fluid structure interaction Shear stress Bioreactor Marrow
The authors would like to acknowledge funding from the Irish Research Council, under the EMBARK program, U.S. National Science Foundation grant CMMI 1100207, Science Foundation Ireland under the Short Term Travel Fellowship and the ORS under the Collaborative Exchange Award.
- 14.David, V., A. Guignandon, A. Martin, L. Malaval, M.-H. Lafage-Proust, A. Rattner, V. Mann, B. Noble, D. B. Jones, and L. Vico. Ex vivo bone formation in bovine trabecular bone cultured in a dynamic 3D bioreactor is enhanced by compressive mechanical strain. Tissue Eng. A 14:117–126, 2008.Google Scholar
- 27.Lambers, F. M., K. Koch, G. Kuhn, D. Ruffoni, C. Weigt, F. A. Schulte, and R. Müller. Trabecular bone adapts to long-term cyclic loading by increasing stiffness and normalization of dynamic morphometric rates. Bone. doi: 10.1016/j.bone.2013.04.016.
- 34.Parfitt, A. M., M. K. Drezner, F. H. Glorieux, J. A. Kanis, H. Malluche, P. J. Meunier, S. M. Ott, and R. R. Recker. Bone histomorphometry: standardization of nomenclature, symbols, and units: report of the asbmr histomorphometry nomenclature committee. J. Bone Miner. Res. 2:595–610, 1987.CrossRefPubMedGoogle Scholar
- 35.DS SIMULIA. Abaqus 6.12 theory manual. Providence, RI: DS SIMULIA Corp., 2012.Google Scholar
- 42.Vaughan, T. J., M. Voisin, G. L. Niebur, and L. M. McNamara. Multiscale modeling of trabecular bone marrow: understanding the micromechanical environment of mesenchymal stem cells during osteoporosis. J. Biomech. Eng. 2015. doi: 10.1115/1.4028986.