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.

Purpose
Microfracture is a well-established treatment procedure for chondral defects in high-demand population with good short-term results. The purpose of our study was to evaluate long-term clinical outcome of microfracture treatment in athletes with full-thickness chondral defects.

Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes.

Objective:The purpose of our study was to determine the effectiveness of cartilage repair utilizing 1-step surgery with bone marrow aspirate concentrate (BMAC) and a collagen I/III matrix (Chondro-...

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One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions Results at 2-Year Follow-up

Background:Chondral lesions in athletically active patients cause considerable morbidity, and treatment with existing cell-based therapies can be challenging. Bone marrow has been shown as a possible source of multipotent stem cells (MSCs) with chondrogenic potential and is easy to harvest during the same surgical procedure.Purpose:To investigate the clinical outcome in a group of active patients with large full-thickness chondral defects of the knee treated with 1-step surgery using bone marrow–derived MSCs and a second-generation matrix.Study Design:Case series; Level of evidence, 4.Methods:From January 2007 to February 2010, 25 patients (average age, 46.5 years) with symptomatic large chondral defects of the knee (International Cartilage Repair Society grade 4) who underwent cartilage transplantation with MSCs and a collagen type I/III matrix were followed up for a minimum of 3 years. The average lesion size was 8.3 cm2. Coexisting injuries were treated during the same surgical procedure in 18 patients...

One-Step Surgery With Multipotent Stem Cells for the Treatment of Large Full-Thickness Chondral Defects of the Knee

>> Purpose: To determine the effectiveness of intra-articular PRP injections in active patients with knee OA and to evaluate clinical outcomes in patients with and without previous surgical treatment for cartilage lesions. Study Design: Case series. Materials and Methods: Fifty patients with knee OA were followed for a minimum of 12 months. All were treated with 2 intra-articular injections of autologous PRP. Twenty-five patients had undergone a previous operative intervention for cartilage lesions, whereas 25 had not. Operated patients had undergone either cartilage shaving or microfracture. Multiple evaluative scores were collected at pretreatment and at 6 and 12 months posttreatment. The required sample of patients was determined beforehand by using statistical power analysis; International Knee Documentation Committee (subjective) score was defined as the primary parameter. A P value of less than 0.05 was considered statistically significant. General linear model–repeated measure test evaluated within-time improvement for each variable for all patients. Post hoc test with Bonferroni adjustment for multiple comparisons was performed to investigate the significance in improvement within time evaluations for each variable for the total sample. The differences in improvement between operated and nonoperated patients were also investigated, as were those between sexes. Results: All patients showed significant improvement in all scores at 6 and 12 months (P < 0.01) and returned to previous activities. No significant difference in improvement was found between the evaluated subgroups (P < 0.01). Conclusions: The PRP treatment showed positive effects in patients with knee OA. Operated and nonoperated patients showed significant improvement by means of diminishing pain and improved symptoms and quality of life. Clinical Relevance: There are only a few studies of PRP treatment for cartilage on osteoarthritic knees. Different PRP products might be more or less appropriate to treat different types of tissues and pathologies. The clinical efficacy of PRP remains under debate, and a standardized protocol has not yet been established.

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Platelet-Rich Plasma Treatment in Symptomatic Patients With Knee Osteoarthritis: Preliminary Results in a Group of Active Patients

ObjectiveTo compare the outcome of matrix-induced autologous chondrocyte implantation (MACI) and bone marrow aspirate concentrate (BMAC)–derived multipotent stem cells (MSCs) implantation in patell...

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Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial.

Georgios Karnatzikos

Papers

Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes.

One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions Results at 2-Year Follow-up

One-Step Surgery With Multipotent Stem Cells for the Treatment of Large Full-Thickness Chondral Defects of the Knee

Platelet-Rich Plasma Treatment in Symptomatic Patients With Knee Osteoarthritis: Preliminary Results in a Group of Active Patients

Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial.