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Τρίτη 12 Ιανουαρίου 2016

Matrix Dimensionality and Stiffness Cooperatively Regulate Osteogenesis of Mesenchymal Stromal Cells

Publication date: Available online 11 January 2016
Source:Acta Biomaterialia
Author(s): Wen-Ting Hsieh, Yi-Shiuan Liu, Yi-hsuan Lee, Marilyn G. Rimando, Keng-hui Lin, Oscar K. Lee
Osteogenic potential of mesenchymal stromal cells (MSCs) is mechanosensitive. It's affected by the mechanical properties of the cellular microenvironment, particularly its mechanical modulus. To explore the effect of mechanical modulus on osteogenesis in the third dimension (3D), this study used a novel polyacrylamide (PA) scaffold whose pores are monodisperse and spherical, the mechanical moduli of which can be tuned across a wide range. It was found that MSCs have similar proliferation rates in PA scaffolds independent of the matrix stiffness. The contractile force exerted by MSCs inside PA scaffolds was strong enough to deform the pores of scaffolds made of more compliant PAs (whose shear modulus, G′scaffold < 4 kPa). Only scaffolds of the highest stiffness (G′scaffold = 12 kPa) can withhold the contraction from MSCs. After osteogenic induction for 21 days, the expression profiles of marker genes showed that PA scaffolds of G′scaffold = 12 kPa promoted osteogenesis of MSCs. Confocal image analysis demonstrated that there are more F-actin cytoskeletons and bundled stress fibers at higher matrix moduli in 2D and 3D. Moreover, the 3D porous structure promotes osteogenesis of MSCs more than 2D flat substrates. Together, the differences of cellular behaviors when cultured in 2D and 3D systems are evident. The PA scaffolds developed in the present study can be used for further investigation into the mechanism of MSC mechanosensing in the 3D context.

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