Regulatory Effects of Mechanical Strain on the Chondrogenic Differentiation of MSCs in a Collagen-GAG Scaffold: Experimental and Computational Analysis
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- McMahon, L.A., Reid, A.J., Campbell, V.A. et al. Ann Biomed Eng (2008) 36: 185. doi:10.1007/s10439-007-9416-5
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The effective treatment of cartilage defects by tissue engineering requires an improved understanding of the effect of mechanical forces on cell differentiation within three-dimensional (3D) matrices. The objective of this study was to investigate the effects of mechanical constraint and cyclic tensile strain on the chondrogenic differentiation of mesenchymal stem cells (MSCs) in a 3D collagen type I-glycosaminoglycan (GAG) scaffold. A multi-station uniaxial stretching bioreactor was fabricated to facilitate application of cyclic strain to the constructs cultured in a chondrogenic medium. Mechanical constraint, created by uniaxial clamping, prevented the cell-mediated contraction of the scaffolds and resulted in a reduction in the rate of GAG synthesis as measured by [35S] sulfate incorporation relative to unconstrained controls. However, the rate of GAG synthesis was increased following application of continuous 10% cyclic tensile loading at 1 Hz for 7 days. A poroelastic finite element analysis of the 3D scaffold computed a maximum fluid flow of 19 μm/s and maximum principal strains of 8% under 10% stretch suggesting these magnitudes were sufficient to mechano-regulate the chondrogenic differentiation process.