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Repair and tissue engineering techniques for articular cartilage

Key Points

  • The limited ability of articular cartilage to regenerate has prompted the development of cell-based tissue engineering techniques, such as autologous chondrocyte implantation

  • The complexity of autologous chondrocyte implantation and contraindications in wide clinical application have driven the development of matrix-assisted chondrocyte implantation, which uses scaffolds to provide mechanical stability and support chondrogenesis

  • To improve neotissue formation, graft maturation and biomechanical integrity, cells can be cultured in vitro before implantation on 3D matrices with exogenous stimuli, such as growth factors

  • Biomaterials such as collagen type I and III membranes are also used in cell-free approaches to enhance cartilage's innate regenerative capacity by functioning as scaffolds for resident progenitor cells

  • Scaffold-free, cell-based techniques to form biomimetic neotissues, which can avoid disadvantages of scaffold use such as limited biocompatibility and release of degradation byproducts, are now in development

  • Despite promising results and advances in cartilage tissue engineering, translation into clinical practice has not yet been achieved, as many challenges remain to be resolved

Abstract

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

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Figure 1: Cartilage regeneration techniques.
Figure 2: Algorithm for treatment of cartilage defects.
Figure 3: New tissue engineering techniques for treating cartilage lesions.
Figure 4: The tissue engineering paradigm.

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Acknowledgements

The authors acknowledge funding from NIH R01 AR061496, NIH R01 DE019666, NIH R01 DE015038, and the California Institute for Regenerative Medicine (CIRM) TR3-05709.

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All authors contributed equally to researching data for the article, substantially contributing to discussion of content, writing and review/editing of the manuscript before submission.

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Correspondence to Kyriacos A. Athanasiou.

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A.H.G. declares that he consults for SANOFI S.A. The other authors declare no competing interests.

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Makris, E., Gomoll, A., Malizos, K. et al. Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 11, 21–34 (2015). https://doi.org/10.1038/nrrheum.2014.157

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