Mechanotransduction in Mesenchymal Stem Cells for Cartilage Tissue Engineering

Cartilage is a viscoelastic tissue that serves to withstand physiologic loads in the body. The prevalence of cartilage degeneration pathologies such as osteoarthritis in the United States coupled with the tissue’s poor native healing capacity call for a cell-based regenerative solution. Current attempts at using multipotent mesenchymal stem cells (MSCs) in a tissue-engineered approach have seen limited success, as MSCs have been shown to deposit extracellular matrix inferior to that produced by adult chondrocytes. In this study, we examine the effects of both short and long-term dynamic deformational loading on MSC extracellular matrix (ECM) production. We also use a novel photocrosslinkable hyaluronic acid (HA) scaffold for MSC seeding. Here, we report that the HA scaffold is capable of supporting MSC growth and chondrogenesis. Moreover, both short and long term dynamic deformational loading applied in conjunction with presence of the chemical morphogen TGFβ3 increase the expression levels of four genes (GalNAc, C4st-1, C4st-2, XT-1) responsible for ECM biosynthesis. Interestingly, prolonged upregulation of the aforementioned genes does not translate to improved mechanical properties or increased proteoglycan content in the ECM. Further studies must therefore be made in order to elucidate the factors responsible for the observed discrepancy and to adjust the current loading regime for optimal ECM biosynthesis.