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 regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. 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.

Articular cartilage was predicted to be one of the first tissues that could successfully be regenerated, but this proved not to be the case. In contrast, bone but also vasculature and cardiac tissues have seen numerous successful reparative approaches, despite consisting of multiple cell and tissue types and thus possessing more complex design requirements. Here, we use bone regeneration successes to highlight cartilage regeneration challenges, namely selecting appropriate cell sources and scaffolds, creating biomechanically suitable tissues, and integrating to native tissue. Also discussed are technologies addressing hurdles of engineering a tissue possessing mechanical properties unmatched in man-made materials and functioning in environments unfavorable to neotissue growth.

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.

Articular cartilage repair and regeneration continue to be largely intractable due to the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are discussed.

Current therapies for articular cartilage defects often result in fibrocartilaginous tissue. To achieve regeneration with hyaline articular cartilage, tissue-engineering approaches employing cell-seeded scaffolds have been investigated. However, limitations of scaffolds include phenotypic alteration of cells, stress-shielding, hindrance of neotissue organization, and degradation product toxicity. This study employs a self-assembling process to produce tissue-engineered constructs over agarose in vitro without using a scaffold. Compared to past studies using various meshes and gels as scaffolding materials, the self-assembly method yielded constructs with comparable GAG and collagen content. By 12 weeks, the self-assembling process resulted in tissue-engineered constructs that were hyaline- like in appearance with histological, biochemical, and biomechanical properties approaching those of native articular cartilage. Overall, constructs contained two thirds more GAG per dry weight than calf articular cartilage. Collagen per dry weight reached more than one third the level of native tissue. IHC and gel electrophoresis showed collagen type II production and absence of collagen type I. More importantly, self-assembled constructs reached well over one third the stiffness of native tissue.