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.

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Surgical and tissue engineering strategies for articular cartilage and meniscus repair.

Purpose: To determine (1) whether platelet-rich plasma (PRP) injection significantly improves validated patient-reported outcomes in patients with symptomatic knee osteoarthritis (OA) at 6 and 12 months postinjection, (2) differences in outcomes between PRP and corticosteroid injections or viscosupplementation or placebo injections at 6 and 12 months postinjection, and (3) similarities and differences in outcomes based on the PRP formulations used in the analyzed studies. Methods: PubMed, Cochrane Central Register of Controlled Trials, SCOPUS, and Sport Discus were searched for Englishlanguage, level I evidence, human in vivo studies on the treatment of symptomatic knee OA with intra-articular PRP compared with other options, with a minimum of 6 months of follow-up. A quality assessment of all articles was performed using the Modified Coleman Methodology Score (average, 83.3/100), and outcomes were analyzed using 2-proportion z-tests. Results: Six articles (739 patients, 817 knees, 39% males, mean age of 59.9 years, with 38 weeks average follow-up) were analyzed. All studies met minimal clinical important difference criteria and showed significant improvements in statistical and clinical outcomes, including pain, physical function, and stiffness, with PRP. All but one study showed significant differences in clinical outcomes between PRP and hyaluronic acid (HA) or PRP and placebo in pain and function. Average pretreatment Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were 52.36 and 52.05 for the PRP and HA groups, respectively (P ¼ .420). Mean post-treatment WOMAC scores for PRP were significantly better than for HA at 3 to 6 months (28.5 and 43.4, respectively; P ¼ .0008) and at 6 to 12 months (22.8 and 38.1, respectively; P ¼ .0062). None of the included studies used corticosteroids. Conclusions: In patients with symptomatic knee OA, PRP injection results in significant clinical improvements up to 12 months postinjection. Clinical outcomes and WOMAC scores are significantly better after PRP versus HA at 3 to 12 months postinjection. There is limited evidence for comparing leukocyte-rich versus leukocyte-poor PRP or PRP versus steroids in this study. Level of Evidence: Level I, systematic review of Level I studies.

Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review

Platelet Rich Plasma (PRP), a blood-derived product rich in growth factors, is a promising treatment for cartilage defects but there is still a lack of clinical evidence. The aim of this study is to show, through a randomized double blind prospective trial, the efficacy of this procedure, by comparing PRP to Hyaluronic Acid (HA) injections for the treatment of knee chondropathy or osteoarthritis (OA). 109 patients (55 treated with HA and 54 with PRP) were treated and evaluated at 12 months of follow-up. The patients were enrolled according to the following inclusion criteria: age> 18 years, history of chronic (at least 4 months) pain or swelling of the knee and imaging findings of degenerative changes of the joint (Kellgren-Lawrence Score up to 3). A cycle of 3 weekly injections was administered blindly. All patients were prospectively evaluated before and at 2, 6, and 12 months after the treatment by: IKDC, EQ-VAS, TEGNER, and KOOS scores. Range of motion and knee circumference changes were measured over time. Adverse events and patient satisfaction were also recorded. Only minor adverse events were detected in some patients, such as mild pain and effusion after the injections, in particular in the PRP group, where a significantly higher post-injective pain reaction was observed (p=0.039). At the follow-up evaluations, both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated. A trend favorable for the PRP group was only found in patients with low grade articular degeneration (Kellgren-Lawrence score up to 2). Results suggest that PRP injections offer a significant clinical improvement up to one year of follow-up. However, conversely to what was shown by the current literature, for middle-aged patients with moderate signs of OA, PRP results were not better than those obtained with HA injections, and thus it should not be considered as first line treatment. More promising results are shown for its use in low grade degeneration, but they still have to be confirmed.

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Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial

Platelet-rich plasma has anti-inflammatory properties and is an important source of molecules that are involved in the repair and regeneration of tissues. PRP therapy, therefore, has great potential for aiding the healing response and repairing joint damage in patients with osteoarthritis. In this comprehensive Review, the authors describe the biological processes of PRP tissue engineering as well as the novel applications and approaches of PRP therapy in the context of targeting joint degeneration. Osteoarthritis (OA) is a common disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture. Autologous blood-derived products, such as platelet-rich plasma (PRP), are key sources of molecules involved in tissue repair and regeneration. These products can deliver a collection of bioactive molecules that have important roles in fundamental processes, including inflammation, angiogenesis, cell migration and metabolism in pathological conditions, such as OA. PRP has anti-inflammatory properties through its effects on the canonical nuclear factor κB signalling pathway in multiple cell types including synoviocytes, macrophages and chondrocytes. PRP contains hundreds of different molecules; cells within the joint add to this milieu by secreting additional biologically active molecules in response to PRP. The net results of PRP therapy are varied and can include angiogenesis, the production of local conditions that favour anabolism in the articular cartilage, or the recruitment of repair cells. However, the molecules found in PRP that contribute to angiogenesis and the protection of joint integrity need further clarification. Understanding PRP in molecular terms could help us to exploit its therapeutic potential, and aid the development of novel treatments and tissue-engineering approaches, for the different stages of joint degeneration.

Platelet-rich plasma for managing pain and inflammation in osteoarthritis

MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment.

Articular cartilage injury in patellofemoral joint presents a clinical challenge and has been identified as a cause of pain, dysfunction and progressive joint degeneration. Any concomitant pathology such as objective or potential patellar instability, muscular dysfunction and biomechanical disorders of the foot and hip can act as a cause of patellofemoral pain syndrome and they should be investigated and addressed when necessary. Cartilage has a poor intrinsic healing potential. Therefore, when left untreated cartilage lesions can progress and lead to chondromalacia and early osteoarthritis (OA).

Pulsed Electromagnetic Fields for the Treatment of Symptomatic Patellofemoral Cartilage Lesions of the Knee

Recurrent patellar dislocation and subluxation can be seen mostly in young and physically active individuals. The etiology of the disorder is varied, and numerous factors have been proposed. More commonly, it occurs during normal activities as a result of dysplastic changes in the patellofemoral system. Constitutional connective tissue weakness also predisposes to patellar dislocation. The spectrum of injury may range from elongation of the medial structures to complete rupture of medial para-patellar soft tissue. A combination of injury to the medial retinaculum and the medial patellofemoral ligament may be present in approximately 65 % of the cases. Patients with lateral patellar dislocation have been treated conservatively with a 15–44 % recurrence rate. Historically, lateral retinacular release was performed with the belief that a tight lateral retinaculum is predisposed to lateral patellar subluxation or dislocation. Since the recognition of the importance of the medial patellofemoral ligament (MPFL), there has been increasing interest in different techniques for managing the medial stabilizer.

Georgios Karnatzikos

Papers

Pulsed Electromagnetic Fields for the Treatment of Symptomatic Patellofemoral Cartilage Lesions of the Knee

Proximal Realignment: Medial Plication

Rehabilitation After Knee Cartilage Transplantation with Autologous Chondrocytes or Stem Cells

Factors Affecting Return to Sport After Anterior Cruciate Ligament Reconstruction

Long-term Results after Microfracture Treatment of Full-thickness Knee Chondral Lesions in Athletes