Figure 6.

Mechanoregulation of hMSC differentiation in microenvironments with fixed elasticity and varied loss tangent. Using 12 kPa hydrogels, in an environment with a stronger elastic character hMSCs take on a highly spread, tensile phenotype with high expression of integrins and focal adhesions that apply high traction forces. This behavior facilitates mechanotransduction and expression of genes and proteins implicated in fibrocartilage and chondrocyte hypertrophy. In an environment with a higher viscous component, hMSCs take on a small, rounded phenotype with low cytoskeletal tension (comparable to a ROCK/Rac1‐inhibited phenotype) and reduced integrin expression that diminishes cell traction forces to the ECM. This response inhibits mechanotransduction and promotes cell–cell contact through cell clustering, with increased N‐cadherin expression and inhibition of β‐catenin activity. Collectively, these responses drive chondrogenesis through increased expression of SOX9 and secretion of cartilage matrix markers. Figure generated using BioRender online software.