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机械限制通过软骨细胞调节软骨基质的形成。

Mechanical confinement regulates cartilage matrix formation by chondrocytes.

机构信息

Department of Mechanical Engineering, Stanford University, Stanford, California 94305, USA.

School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.

出版信息

Nat Mater. 2017 Dec;16(12):1243-1251. doi: 10.1038/nmat4993. Epub 2017 Oct 2.

Abstract

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.

摘要

水凝胶中包含软骨细胞可形成软骨组织等效物,为修复受损软骨提供了解决方案。先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并改变软骨细胞表型。在这里,我们研究了粘弹性水凝胶在三维(3D)培养软骨细胞中的应用,其中应力随时间松弛并表现出蠕变。我们发现,更快的松弛促进了由软骨细胞形成的互连软骨基质体积的显著增加。在松弛较慢的凝胶中,弹性应力限制细胞体积扩张导致 IL-1β 的分泌增加,进而强烈上调与软骨降解和细胞死亡相关的基因。由于水凝胶中不呈现细胞粘附配体,这些结果表明细胞对细胞体积限制的感知是 3D 培养中粘附独立的机械转导机制,并强调了应弛豫作为软骨组织工程的关键设计参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df8b/5701824/58ebcc590a26/nihms902933f1.jpg

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