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  • Review Article
  • Published:

Functional articular cartilage repair: here, near, or is the best approach not yet clear?

Nature Reviews Rheumatology volume 9, pages 277–290 (2013)Cite this article

Subjects

Abstract

In this Review we describe three approaches for cartilage tissue repair at the rheumatology–orthopaedics interface: disease-modifying osteoarthritis (OA) drug (DMOAD) treatment; cell-based therapies, and intrinsic cartilage repair by joint distraction. DMOADs can slow the progression of joint damage. Cell-based therapies have evolved to do the same, through selection of the most potent cell types (and combinations thereof), as well as identification of permissive boundary conditions for indications. Joint distraction techniques, meanwhile, have now demonstrated the capacity to stimulate actual intrinsic tissue repair. Although this progress is promising, true biological joint reconstruction remains distant on the developmental pathway of 'regenerative medicine'. Prolonged functional repair—that is, cure of diseases such as OA—remains an unmet medical need and scientific challenge, for which comparative and constructive interaction between these physical, chemical and cellular approaches will be required. Careful selections of patients and combinations of approaches will need to be made and tested to demonstrate their cost-effectiveness. Only with such rational and integrated assessment of outcomes will the promising results of these approaches be consolidated in clinical practice.

Key Points

  • The quest for disease-modifying osteoarthritis drugs (DMOADs) is becoming increasingly fruitful; modalities that alter bone turnover—and, indirectly, cartilage damage—seem to be most effective

  • Long-term outcomes of cell-based therapies are good; quality has improved with European advanced therapeutic medicinal products regulation; the current goal is combining cartilage components, mesenchymal stem cells and trophic factors into a one-stage therapy

  • Joint distraction can induce tissue-structure modification in degenerated knee joints, accompanied by prolonged symptomatic improvement that supports the concept of cartilage repair translating into real clinical benefit

  • Joint distraction itself might represent an integrated approach to tackling the separate chondroprotective, chondroreparative and bone turnover-modifying mechanisms targeted by DMOADs and cell-based therapies

  • Combining DMOAD and cell-based therapies with joint distraction might be a worthwhile approach towards functional tissue repair, as distraction provides a temporary biomechanical joint homeostasis that facilities repair mechanisms

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Figure 1: Cell-based therapy approaches.
Figure 2: Visualization of fixed knee-joint distraction apparatus.
Figure 3: Homeostatic joint mechanisms implicated in the effects of joint distraction on degenerative joint disease.

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Acknowledgements

We thank A. M. van Laar for the literature search.

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Authors and Affiliations

  1. Department of Rheumatology & Clinical Immunology, University Medical Centre Utrecht, P.O. Box 85500, Utrecht, 3508 GA, The Netherlands

    Simon C. Mastbergen & Floris P. J. G. Lafeber

  2. Department of Orthopaedics, University Medical Centre Utrecht, P.O. Box 85500, Utrecht, 3508 GA, The Netherlands

    Daniël B. F. Saris

  3. Department of Reconstructive Medicine, MIRA Institute, University of Twente, Drienerlolaan 5, Enschede, 7522 NB, The Netherlands

    Daniël B. F. Saris

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  1. Simon C. Mastbergen
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  2. Daniël B. F. Saris
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  3. Floris P. J. G. Lafeber
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Contributions

All authors made substantial contributions to researching data for the article, writing the article and to review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Floris P. J. G. Lafeber.

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Competing interests

D. B. F. Saris declares that he has acted as a consultant for, received speakers' honoraria from, and received grant/research support from Sanofi and Smith & Nephew, has acted as a consultant for Regentis, and has a teaching agreement with and has received grant support from TiGenix. S. C. Mastbergen and F. P. J. G. Lafeber declare no competing interests.

Supplementary information

Supplementary Table 1

Studies of joint distraction in animal models of knee joint and vertebral disc degeneration. (DOC 55 kb)

Supplementary Figure 1

Search, inclusion and exclusion strategies applied to the identification of publications relevant to the section on joint distraction. (DOC 330 kb)

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Mastbergen, S., Saris, D. & Lafeber, F. Functional articular cartilage repair: here, near, or is the best approach not yet clear?. Nat Rev Rheumatol 9, 277–290 (2013). https://doi.org/10.1038/nrrheum.2013.29

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