Aged bovine chondrocytes display a diminished capacity to produce a collagen-rich, mechanically functional cartilage extracellular matrix

Authors

  • Nicolas Tran-Khanh,

    1. Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada H3C 3A7
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  • Caroline D. Hoemann,

    1. Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada H3C 3A7
    2. Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada H3C 3A7
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  • Marc D. McKee,

    1. Faculty of Dentistry and Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada H3A 2B2
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  • Janet E. Henderson,

    1. Faculty of Medicine, Centre for Bone and Periodontal Research, McGill University, Montreal, Quebec, Canada H3A 1 A4
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  • Michael D. Buschmann

    Corresponding author
    1. Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada H3C 3A7
    2. Department of Chemical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada H3C 3A7
    • Department of Chemical and Biomedical Engineering, Ecole Polytechnique, PO 6079 Station Centre-ville, Montreal, Quebec, Canada H3C 3A7. Tel.: +1 514 340 4711x4931; fax: +1 514 340 2980
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Abstract

Most fundamental studies in cartilage tissue engineering investigate the ability of chondrocytes from young animals to produce cartilaginous matrix under various conditions, while current clinical applications such as autologous chondrocyte implantation, use chondrocytes from donors that are decades past skeletal maturity. Previous investigations have suggested that several characteristics of primary chondrocytes are age-dependent but none have quantified cell proliferation, proteoglycan synthesis and accumulation, collagen synthesis and accumulation, compressive and tensile mechanical properties in order to examine the effects of donor age on all of these parameters. We enzymatically isolated primary bovine chondrocytes from fetal, young and aged animals and cultured these cells in agarose gels to assess the above-mentioned properties. We found that fetal and young (but still skeletally mature i.e. 18-month-old bovine) chondrocytes behaved similarly, while aged chondrocytes (5- to 7-year-old bovine) displayed diminished proliferation (∼2× less), a slightly reduced proteoglycan accumulation per cell (∼20%), and significantly less collagen accumulation per cell (∼55%) compared to the younger cells. Histological observations and mechanical properties supported these findings, where a particularly significant reduction in tensile stiffness produced by aged chondrocytes compared to younger cells was observed. Our findings suggest that donor age is an important factor in determining the outcome and potential success when tissue-engineered cartilage is produced from articular chondrocytes. More specifically, primary chondrocytes from aged donors may not possess sufficient capacity to produce the extracellular matrix that is required for a mechanically resilient tissue. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

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