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  • Review Article
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Recent advancements in cartilage tissue engineering innovation and translation

Nature Reviews Rheumatology volume 20, pages 323–346 (2024)Cite this article

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Abstract

Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhibit considerable limitations. For example, of the cell-based products that are available globally, only one is marketed for non-knee indications, none are indicated for severe osteoarthritis or rheumatoid arthritis, and only one is approved for marketing in the USA. However, advances in cartilage tissue engineering might now finally lead to the development of new cartilage repair products. To understand the potential in this field, it helps to consider the current landscape of tissue-engineered products for articular cartilage repair and particularly cell-based therapies. Advances relating to cell sources, bioactive stimuli and scaffold or scaffold-free approaches should now contribute to progress in therapeutic development. Engineering for an inflammatory environment is required because of the need for implants to withstand immune challenge within joints affected by osteoarthritis or rheumatoid arthritis. Bringing additional cartilage repair products to the market will require an understanding of the translational vector for their commercialization. Advances thus far can facilitate the future translation of engineered cartilage products to benefit the millions of patients who suffer from cartilage injuries and arthritides.

Key points

  • Of the cell-based articular cartilage products available globally, only one is marketed for non-knee indications, none are marketed for severe osteoarthritis and none are marketed for rheumatoid arthritis.

  • Cartilage tissue engineering advances include making scaffold-based and scaffold-free cartilage with robust mechanical properties that might enable implants to survive in the loaded-joint environment.

  • Tissue engineering cartilage implants to survive the inflammatory environment through the use of immunomodulatory biomaterials and synthetic biology is a current research highlight.

  • Most large-animal studies for cartilage tissue engineering in the knee use porcine, caprine and ovine models, whereas porcine models are used for temporomandibular joint studies.

  • Several tissue-engineered cartilage products in clinical development use allogeneic cell sources; the use of cell banks that employ allogeneic cells can improve reproducibility and consistency.

  • Owing to the arduous nature of translating biologics, academic researchers should familiarize themselves with the translational vector (including regulatory, manufacturing, funding and intellectual property aspects) to facilitate clinical development.

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Fig. 1: Strategies for articular cartilage tissue engineering.
Fig. 2: Approaches for tissue engineering cartilage in an inflammatory environment.
Fig. 3: The translational vector for tissue-engineered cartilage products.

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Acknowledgements

This work was supported by the US National Institutes of Health (NIH) R01 AR067821 (K.A.A.), NIH R01 AR078389 (K.A.A.), NIH TL1 TR001415 (R.C.N.) and NIH F32 DE032896 (B.J.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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  1. These authors contributed equally: Rachel C. Nordberg, Benjamin J. Bielajew.

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  1. Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA

    Rachel C. Nordberg, Benjamin J. Bielajew, Takumi Takahashi, Shuyan Dai, Jerry C. Hu & Kyriacos A. Athanasiou

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Contributions

R.C.N., B.J.B., T.T. and S.D. researched data for the article. All authors contributed substantially to discussion of the content. All authors wrote the article. R.C.N., B.J.B., J.C.H. and K.A.A reviewed and/or edited the manuscript before submission.

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Correspondence to Kyriacos A. Athanasiou.

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K.A.A. and J.C.H. have an equity interest in Cartilage, Inc. Their relationship with Cartilage, Inc. has been reviewed and approved by the University of California, Irvine in accordance with its conflict-of-interest policies. The remaining authors declare no competing interests.

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Nature Reviews Rheumatology thanks Adetola Adesida, who co-reviewed with Hilda Ma; Elizabeth Vinod; and the other, anonymous, reviewers for their contribution to the peer review of this work.

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clinicaltrials.gov: https://clinicaltrials.gov

International Council for Harmonisation: https://www.ich.org/page/quality-guidelines

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Nordberg, R.C., Bielajew, B.J., Takahashi, T. et al. Recent advancements in cartilage tissue engineering innovation and translation. Nat Rev Rheumatol 20, 323–346 (2024). https://doi.org/10.1038/s41584-024-01118-4

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