Mechanical confinement regulates cartilage matrix formation by chondrocytes.
Mechanical confinement regulates cartilage matrix formation by chondrocytes.
复制标题
DOI：
10.1038/nmat4993
复制
发表时间：
2017-12
期刊：
影响因子：
41.2
通讯作者：
Chaudhuri O
中科院分区：
文献类型：
--
作者：
Lee HP;Gu L;Mooney DJ;Levenston ME;Chaudhuri O
由含有软骨细胞的水凝胶形成的软骨组织等价物可以为修复受损的软骨提供一种解决方案。以前的方法通常使用弹性水凝胶。然而，弹性应力可能会限制软骨基质的形成，改变软骨细胞的表型。在这里，我们研究了粘弹性水凝胶用于软骨细胞的3D培养，在这种凝胶中，应力随着时间的推移而松弛，并且表现出蠕变。我们发现，更快的松弛促进了由软骨细胞形成的相互连接的软骨基质体积的显着增加。在较慢的松弛凝胶中，弹性应力限制细胞体积扩张导致IL-1β的分泌增加，进而推动与软骨降解和细胞死亡相关的基因的强烈上调。由于水凝胶不提供细胞黏附配体，这些结果揭示了细胞对细胞体积限制的感知是3D培养中一种与黏附无关的力学转导机制，并强调了应力松弛是软骨组织工程的关键设计参数。
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 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.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Chaudhuri O;Gu L;Darnell M;Klumpers D;Bencherif SA;Weaver JC;Huebsch N;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
56.9
作者：
LAGERWERFF, J;EAGLE, HE;OGATA, G
通讯作者：
OGATA, G
影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA