Mesenchymal stem cells (MSCs) are a multi-potential cell type that can differentiate toward a variety of tissue-specific phenotypes, including cartilage. Given their chondrogenic potential, MSCs are a promising cell source for cartilage tissue engineering (TE). However, while MSCs readily undergo chondrogenesis in 3D culture and deposit a cartilage-like matrix, the mechanical properties of MSC-seeded constructs are greatly inferior to chondrocyte-seeded constructs similarly maintained [1]. To date, optimization strategies for enhancing functional MSC chondrogenesis, including increasing seeding density and transient application of growth factor, have shown limited success [3]. Using microarray analysis, we have recently demonstrated that mis-expression of certain genes, including lubricin, chondromodulin and RGD-CAP, a collagen associated protein, may underlie this disparity in mechanical function [2]. In this study, we examined dynamic compression as an alternative method to enhance MSC differentiation. Previous work using chondrocyte-based constructs have demonstrated that matrix biosynthesis and mechanical properties were improved with the application of cyclic compression [4]. Furthermore, upregulation of lubricin was observed when surface motion was applied to chondrocyte-seeded porous scaffolds [5]. While significant effort has gone toward optimizing loading parameters to direct tissue growth of chondrocyte-based constructs, few studies have examined the effects of mechanical stimulation on MSC-based constructs. Some have demonstrated positive effects on MSC chondrogenesis with application of compressive loading [6, 7], while others have shown that long-term loading may adversely affect the developing mechanical properties of MSC-seeded constructs [8]. In this study, we examined the effects of repeated dynamic compressive loading on MSC chondrogenesis and showed that mechanical properties and gene expression were modulated by this loading modality.

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