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  • Review Article
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Surgical and tissue engineering strategies for articular cartilage and meniscus repair

Nature Reviews Rheumatology volume 15, pages 550–570 (2019)Cite this article

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Abstract

Injuries to articular cartilage and menisci can lead to cartilage degeneration that ultimately results in arthritis. Different forms of arthritis affect ~50 million people in the USA alone, and it is therefore crucial to identify methods that will halt or slow the progression to arthritis, starting with the initiating events of cartilage and meniscus defects. The surgical approaches in current use have a limited capacity for tissue regeneration and yield only short-term relief of symptoms. Tissue engineering approaches are emerging as alternatives to current surgical methods for cartilage and meniscus repair. Several cell-based and tissue-engineered products are currently in clinical trials for cartilage lesions and meniscal tears, opening new avenues for cartilage and meniscus regeneration. This Review provides a summary of surgical techniques, including tissue-engineered products, that are currently in clinical use, as well as a discussion of state-of-the-art tissue engineering strategies and technologies that are being developed for use in articular cartilage and meniscus repair and regeneration. The obstacles to clinical translation of these strategies are also included to inform the development of innovative tissue engineering approaches.

Key points

  • Current cartilage repair techniques include surgery and cell-based therapies for articular cartilage, and surgery for meniscus repair; however, such treatments have limited capacity to induce regeneration.

  • Tissue engineering strategies to create cartilage using a variety of cell sources and exogenous stimuli have made advances towards replicating the native architecture and functional properties of cartilage.

  • Most cell-based tissue engineering products currently in clinical trials are indicated for knee articular cartilage, with very few indicated for hip cartilage or the meniscus.

  • Allogeneic and non-articulating cartilage might serve as additional cell sources for engineered articular cartilage and meniscus products.

  • The pro-inflammatory environment of arthritic joints and issues surrounding neotissue integration need to be addressed to maximize the clinical translation of new tissue-engineered products.

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Fig. 1: Articular cartilage structure and treatment methods.
Fig. 2: Meniscus structure and treatment methods.
Fig. 3: Advances in tissue engineering strategies for articular cartilage and meniscus.
Fig. 4: Challenges to the clinical translation of engineered cartilage and meniscus products.

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Acknowledgements

The work of the authors was supported by the National Institutes of Health (grants R01AR067821 and R01AR071457 to K.A.A.), and by funds provided by the Henry Samueli Chair in Engineering.

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Nature Reviews Rheumatology thanks H. Madry, E. Kon and D. J. Kelly for their contribution to the peer review of this work.

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Authors and Affiliations

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

    Heenam Kwon, Wendy E. Brown, Jerry C. Hu & Kyriacos A. Athanasiou

  2. Department of Orthopaedic Surgery, University of California Davis Medical Center, Sacramento, CA, USA

    Cassandra A. Lee

  3. Department of Orthopaedic Surgery, University of California Irvine Medical Center, Orange, CA, USA

    Dean Wang

  4. Division of Sports Medicine, Department of Orthopaedic Surgery, New England Baptist Hospital, Tufts University School of Medicine, Boston, MA, USA

    Nikolaos Paschos

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Contributions

H.K., W.E.B., C.A.L., D.W., N.P. and J.C.H. researched data for this article. All authors provided substantial contributions to the discussion of content, wrote the article and reviewed and/or edited the article before submission. H.K. and W.E.B. contributed equally to this article.

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Correspondence to Kyriacos A. Athanasiou.

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W.E.B. declares she is the Director of Outreach and a social media contributor for Science Cheerleaders, Incorporated. C.A.L. declares she is on the advisory board of Vericel. N.P. declares he is an associate editor of the Arthroscopy Journal. K.A.A. declares he is on the scientific advisory board of Histogenics. K.A.A., J.C.H., H.K. and W.E.B. declare they are listed as co-authors of submitted US patent applications (16/136,894 and 16/137,120). D.W. declares no competing interests.

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Glossary

Debridement

The removal of damaged tissue and/or torn fragments from a defect.

Hoop stresses

Compressive forces experienced by the meniscus in the circumferential direction.

Rasping

Mechanical scraping to expose fresh and/or bleeding tissue.

Radial trephination

Puncturing small holes into the joint lining and/or synovium and into the tissue to stimulate healing.

Bone plugs

Created or fashioned bone cylinders containing the enthesis of the meniscal roots.

Common bone bridge

Excised bone containing and preserving the anatomic relationship between the anterior and posterior meniscal horns (also known as ‘slot’).

Hemi-plateau

Half of the tibial plateau, containing the articular surface, subchondral bone and meniscus with root attachments.

Lysholm score

A scoring system used to measure changes in limping, support, locking, instability, pain, swelling, stair climbing and squatting (originally developed to evaluate outcomes of knee ligament surgery).

Stress shielding

Protection of tissue from normal mechanical stresses by the presence of a much stiffer implant, often resulting in tissue loss.

Self-assembling process

A scaffold-free technology that produces tissues that demonstrate spontaneous organization without external forces via the minimization of free energy through cell-to-cell interactions.

Anisotropy

Having directionally dependent properties.

International Knee Documentation Committee (IKDC) score

A scoring system used to measure symptoms, sports and daily activities, current knee function and function before injury.

International Cartilage Repair Society (ICRS)-Cartilage Repair Assessment System

A tool used to macroscopically evaluate the quality of cartilage repair tissue.

International Hip Outcome Tool

A tool used to measure symptoms, functional limitation, work-related concerns, sports and recreational activities, and social, emotional and lifestyle concerns using a visual analogue scale.

Tegner–Lysholm score

A patient-reported score of the effect of knee pain and stability on daily life.

Range of motion (ROM) score

A measurement of the range of flexion and extension of a joint.

Tribological properties

Functional properties relating to friction and lubrication of tissues.

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Kwon, H., Brown, W.E., Lee, C.A. et al. Surgical and tissue engineering strategies for articular cartilage and meniscus repair. Nat Rev Rheumatol 15, 550–570 (2019). https://doi.org/10.1038/s41584-019-0255-1

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