Regulatory effects of mechanical strain on the chondrogenic differentiation of MSCs in a collagen-GAG scaffold: experimental and computational analysis.
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 microm/s and maximum principal strains of 8% under 10% stretch suggesting these magnitudes were sufficient to mechano-regulate the chondrogenic differentiation process.
McMahon
Louise A
LA
Trinity Centre for Bioengineering, School of Engineering, Trinity College, Parsons Building, Dublin 2, Ireland.
Reid
Alan J
AJ
Campbell
Veronica A
VA
Prendergast
Patrick J
PJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology*; D024042:Collagen Type I / Q000502:physiology*; D003198:Computer Simulation; D006025:Glycosaminoglycans / Q000502:physiology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D013718:Tensile Strength
D024042:Collagen Type I; D006025:Glycosaminoglycans