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Regulatory Effects of Mechanical Strain on the Chondrogenic Differentiation of MSCs in a Collagen-GAG Scaffold: Experimental and Computational Analysis

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Abstract

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.

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Acknowledgments

This work was funded by the Irish Research Council for Science, Engineering and Technology: funded by the National Development Plan and by the Programme for Research in Third Level Institutions (Trinity Centre for Bioengineering) administered by the Higher Education Authority, Ireland. The authors would like to thank Dr. Fergal O’Brien and Mr. Matthew Haugh (RCSI, Dublin) and Integra for their generous donation of the scaffolds, Mr. Gabriel Nicholson (Trinity Centre for Bioengineering) for the fabrication of the multi-station bioreactor, and Dr. Thomas Connor and Ms. Noreen Boyle (Trinity College Institute of Neuroscience, Trinity College), for their advice on flow cytometry.

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Authors and Affiliations

  1. Trinity Centre for Bioengineering, School of Engineering, Trinity College, Parsons Building, Dublin, 2, Ireland

    Louise A. McMahon, Veronica A. Campbell & Patrick J. Prendergast

  2. Department of Mechanical Engineering, School of Engineering, Trinity College, Parsons Building, Dublin, 2, Ireland

    Alan J. Reid & Patrick J. Prendergast

  3. Department of Physiology, School of Medicine, Trinity College, Parsons Building, Dublin, 2, Ireland

    Veronica A. Campbell

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  1. Louise A. McMahon
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  2. Alan J. Reid
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  4. Patrick J. Prendergast
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Correspondence to Patrick J. Prendergast.

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Presented, in part, at the American Society of Mechanical Engineers Summer Bioengineering Conference, Florida, June 2006, and the Orthopaedic Research Society, San Diego, February 2007.

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McMahon, L.A., Reid, A.J., Campbell, V.A. et al. Regulatory Effects of Mechanical Strain on the Chondrogenic Differentiation of MSCs in a Collagen-GAG Scaffold: Experimental and Computational Analysis. Ann Biomed Eng 36, 185–194 (2008). https://doi.org/10.1007/s10439-007-9416-5

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