Article

Mechanical confinement regulates cartilage matrix formation by chondrocytes

  • Nature Materials volume 16, pages 12431251 (2017)
  • doi:10.1038/nmat4993
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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.

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Acknowledgements

The authors acknowledge the help of R. Stowers, J. Lee, A. Arvayo, J. Lai, G. Baylon, M. Aliyeh, K. Wisdom, S. Nam, S. Lee, D. No, J. Yu, K. Kim, K. Han and all members of the Chaudhuri lab, and thank D. Weitz (Harvard University) for helpful discussions. This work was supported by the Jeongsong Cultural Foundation (to H.L.), NIH grant R01 DE013033 (to D.J.M.), and DARPA grant D14AP00044 (to O.C.).

Author information

Affiliations

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

    • Hong-pyo Lee
    • , Marc E. Levenston
    •  & Ovijit Chaudhuri
  2. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA

    • Luo Gu
    •  & David J. Mooney
  3. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA

    • Luo Gu
    •  & David J. Mooney

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Contributions

H.L., M.E.L. and O.C. designed the experiments. H.L. conducted all experiments and analysed the data. L.G. and D.J.M. contributed to the materials design and materials. H.L. and O.C. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ovijit Chaudhuri.

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