Effects of hydrostatic pressure and deviatoric stress on human articular chondrocytes for designing neo-cartilage...

Autologous chondrocyte implantation is a promising therapy for the treatment of the articular cartilage defects. Recently, we have developed a three-dimensional chondrocyte construct manufactured with a collagen gel/sponge scaffold and cyclic hydrostatic pressure. However, the roles of various mechanical stresses, specifically hydrostatic pressure and deviatoric stress, as well as poststress loading, were unclear on metabolic function in chondrocytes. We hypothesized that hydrostatic pressure and deviatoric stresses each alter individual metabolic characteristics of chondrocytes. We embedded human articular chondrocytes within an agarose hydrogel and applied hydrostatic pressure and/or deviatoric stress individually or simultaneously for 4 days. Subsequently, we kept the cell constructs without stress for an additional 3 days. With hydrostatic pressure and/or deviatoric stress, more cells proliferated significantly than no stress (p < .05) and more cells proliferated near the inner side of the construct than the outer (p < .05). Cartilage specific aggrecan core protein and collagen type II were upregulated significantly after off-loading hydrostatic pressure alone at Day 7 (p < .05). On the other hand, these molecules were upregulated significantly immediately after deviatoric stress alone and combined with hydrostatic pressure at Day 4 (p < .05). Tissue inhibitor of metalloproteinase-2 was upregulated significantly after off-loading hydrostatic pressure alone and combined deviatoric stress at Day 7 (p < .05). Metalloproteinnase-13 was upregulated significantly with deviatoric stress at Day 4 (p < .05) and combined with hydrostatic pressure at Day 4. These results suggest that metabolic functions are regulated by the combination of hydrostatic pressure and deviatoric stress and by the timing of stress loading.