Cartilage tissue equivalents formed from hydrogels containing chondrocytes could provide a solution for replacing damaged cartilage. Previous approaches have often utilized elastic hydrogels. However, elastic stresses may restrict cartilage matrix formation and alter the chondrocyte phenotype. Here we investigated the use of viscoelastic hydrogels, in which stresses are relaxed over time and which exhibit creep, for three-dimensional (3D) culture of chondrocytes. We found that faster relaxation promoted a striking increase in the volume of interconnected cartilage matrix formed by chondrocytes. In slower relaxing gels, restriction of cell volume expansion by elastic stresses led to increased secretion of IL-1β, which in turn drove strong up-regulation of genes associated with cartilage degradation and cell death. As no cell-adhesion ligands are presented by the hydrogels, these results reveal cell sensing of cell volume confinement as an adhesion-independent mechanism of mechanotransduction in 3D culture, and highlight stress relaxation as a key design parameter for cartilage tissue engineering.

由含有软骨细胞的水凝胶形成的软骨组织等价物可为替换受损的软骨提供解决方案。先前的方法经常利用弹性水凝胶。但是，弹性应力可能会限制软骨基质的形成并改变软骨细胞的表型。在这里，我们研究了软骨细胞三维（3D）培养的粘弹性水凝胶的使用，其中应力随着时间的流逝而松弛并且呈现蠕变。我们发现，更快的放松促进了软骨细胞形成的相互连接的软骨基质的体积显着增加。在较慢的松弛凝胶中，弹性应力对细胞体积膨胀的限制导致IL-1β分泌增加，进而促使与软骨降解和细胞死亡相关的基因强烈上调。