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      Surgical and tissue engineering strategies for articular cartilage and meniscus repair

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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, therefore it is 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, 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.

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          Most cited references156

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          A stem cell-based approach to cartilage repair.

          Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor β subunit (CBFβ), and induces chondrogenesis by regulating the CBFβ-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis.
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            Microfracture: surgical technique and rehabilitation to treat chondral defects.

            Full-thickness articular cartilage defects rarely heal spontaneously. Some patients may not have clinically significant problems from chondral defects, but most eventually have degenerative changes. Techniques to treat chondral defects include abrasion, drilling, autografts, allografts, and cell transplantation. The senior author (JRS) developed the microfracture technique to enhance chondral resurfacing by providing a suitable environment for new tissue formation and taking advantage of the body's own healing potential. Microfracture has been done in more than 1800 patients. Specially designed awls are used to make multiple perforations, or microfractures, into the subchondral bone plate. Perforations are made as close together as possible, but not so close that one breaks into another. They usually are approximately 3 to 4 mm apart. The integrity of the subchondral bone plate must be maintained. The released marrow elements (including mesenchymal stem cells, growth factors, and other healing proteins) form a surgically induced super clot that provides an enriched environment for new tissue formation. The rehabilitation program is crucial to optimize the results of the surgery. It promotes the ideal physical environment for the marrow mesenchymal stem cells to differentiate into articular cartilagelike cells, ultimately leading to development of a durable repair cartilage that fills the original defect.
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              Articular cartilage defects in 1,000 knee arthroscopies.

              Focal chondral or osteochondral defects can be painful and disabling, have a poor capacity for repair, and may predispose patients for osteoarthritis. New surgical procedures that aim to reestablish hyaline cartilage have been introduced and the results seem promising. The purpose of this study is to provide reliable data on chondral and osteochondral defects in patients with symptomatic knees requiring arthroscopy and to calculate the prevalence of patients who might benefit from cartilage repair surgery. Prospective study. One thousand consecutive knee arthroscopies were included in this study. Immediately after each arthroscopy, the surgeon completed a questionnaire providing detailed information about the findings. Chondral and osteochondral lesions were classified in accordance with the system recommended by the International Cartilage Repair Society (ICRS). Chondral or osteochondral lesions (of any type) were found in 61% of the patients. Focal chondral or osteochondral defects were found in 19% of the patients. In these patients, 61% related their current knee problem to a previous trauma, and a concomitant meniscal or anterior cruciate ligament injury was found in 42% (n = 81) and 26% (n = 50), respectively. The mean chondral or osteochondral total defect area was 2.1 cm(2) (range, 0.5 to 12; standard deviation [SD], 1.5). The main focal chondral or osteochondral defect was found on the medial femoral condyle in 58%, patella in 11%, lateral tibia in 11%, lateral femoral condyle in 9%, trochlea in 6%, and medial tibia in 5%. It has been suggested that cartilage repair surgery may be most suitable in patients younger than 40 to 50 years old. A single, well-defined ICRS grade III or IV defect with an area of at least 1 cm(2) in a patient younger than 40, 45, or 50 years accounted for 5.3%, 6.1%, and 7.1% of all arthroscopies, respectively. Our study supports the contention that articular cartilage defects are common. It has the advantages of a prospective design and use of a new classification system recommended by the ICRS. This modern system focuses on objectively measurable parameters of the lesion's extent and not its surface appearance.
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                Author and article information

                Journal
                Nature Reviews Rheumatology
                Nat Rev Rheumatol
                Springer Science and Business Media LLC
                1759-4790
                1759-4804
                July 11 2019
                Article
                10.1038/s41584-019-0255-1
                7192556
                31296933
                b0a1fe64-064c-445e-94cd-ddf4c0bc2ea3
                © 2019

                http://www.springer.com/tdm

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