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      Biology of platelet-rich plasma and its clinical application in cartilage repair

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      1 , 2 , 1 , 2 ,
      Arthritis Research & Therapy
      BioMed Central

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          Abstract

          Platelet-rich plasma (PRP) is an autologous concentrated cocktail of growth factors and inflammatory mediators, and has been considered to be potentially effective for cartilage repair. In addition, the fibrinogen in PRP may be activated to form a fibrin matrix to fill cartilage lesions, fulfilling the initial requirements of physiological wound healing. The anabolic, anti-inflammatory and scaffolding effects of PRP based on laboratory investigations, animal studies, and clinical trials are reviewed here. In vitro, PRP is found to stimulate cell proliferation and cartilaginous matrix production by chondrocytes and adult mesenchymal stem cells (MSCs), enhance matrix secretion by synoviocytes, mitigate IL-1β-induced inflammation, and provide a favorable substrate for MSCs. In preclinical studies, PRP has been used either as a gel to fill cartilage defects with variable results, or to slow the progression of arthritis in animal models with positive outcomes. Findings from current clinical trials suggest that PRP may have the potential to fill cartilage defects to enhance cartilage repair, attenuate symptoms of osteoarthritis and improve joint function, with an acceptable safety profile. Although current evidence appears to favor PRP over hyaluronan for the treatment of osteoarthritis, the efficacy of PRP therapy remains unpredictable owing to the highly heterogeneous nature of reported studies and the variable composition of the PRP preparations. Future studies are critical to elucidate the functional activity of individual PRP components in modulating specific pathogenic mechanisms.

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          Most cited references98

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          Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).

          The topical use of platelet concentrates is recent and its efficiency remains controversial. Several techniques for platelet concentrates are available; however, their applications have been confusing because each method leads to a different product with different biology and potential uses. Here, we present classification of the different platelet concentrates into four categories, depending on their leucocyte and fibrin content: pure platelet-rich plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; leucocyte- and platelet-rich plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan or GPS PRP; pure plaletet-rich fibrin (P-PRF), such as Fibrinet; and leucocyte- and platelet-rich fibrin (L-PRF), such as Choukroun's PRF. This classification should help to elucidate successes and failures that have occurred so far, as well as providing an objective approach for the further development of these techniques.
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            Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway.

            N Perkins (2006)
            The diverse cellular and biological functions of the nuclear factor kappa B (NF-kappaB) pathway, together with the catastrophic consequences of its aberrant regulation, demand specific and highly regulated control of its activity. As described in this review, regulation of the NF-kappaB pathway is brought about through multiple post-translational modifications that control the activity of the core components of NF-kappaB signaling: the IkappaB kinase (IKK) complex, the IkappaB proteins and the NF-kappaB subunits themselves. These regulatory modifications, which include phosphorylation, ubiquitination, acetylation, sumoylation and nitrosylation, can vary, depending on the nature of the NF-kappaB-inducing stimulus. Moreover, they frequently have distinct, sometimes antagonistic, functional consequences and the same modification can have different effects depending on the context. Given the important role of NF-kappaB in human health and disease, understanding these pathways will not only provide valuable insights into mechanism and function, but could also lead to new drug targets and the development of diagnostic and prognostic biomarkers for many pathological conditions.
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              The role of growth factors in cartilage repair.

              Full-thickness chondral defects and early osteoarthritis continue to present major challenges for the patient and the orthopaedic surgeon as a result of the limited healing potential of articular cartilage. The use of bioactive growth factors is under consideration as a potential therapy to enhance healing of chondral injuries and modify the arthritic disease process. We reviewed the role of growth factors in articular cartilage repair and identified specific growth factors and combinations of growth factors that have the capacity to improve cartilage regeneration. Additionally, we discuss the potential use of platelet-rich plasma, autologous-conditioned serum, and bone marrow concentrate preparations as methods of combined growth factor delivery. A PubMed search was performed using key words cartilage or chondrocyte alone and in combination with growth factor. The search was open for original manuscripts and review papers and open for all dates. From these searches we selected manuscripts investigating the effects of growth factors on extracellular matrix synthesis and excluded those investigating molecular mechanisms of action. By modulating the local microenvironment, the anabolic and anticatabolic effects of a variety of growth factors have demonstrated potential in both in vitro and animal studies of cartilage injury and repair. Members of the transforming growth factor-β superfamily, fibroblast growth factor family, insulin-like growth factor-I, and platelet-derived growth factor have all been investigated as possible treatment augments in the management of chondral injuries and early arthritis. The application of growth factors in the treatment of local cartilage defects as well as osteoarthritis appears promising; however, further research is needed at both the basic science and clinical levels before routine application.
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                Author and article information

                Contributors
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central
                1478-6354
                1478-6362
                2014
                25 February 2014
                25 August 2014
                : 16
                : 1
                : 204
                Affiliations
                [1 ]Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233, China
                [2 ]Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
                Article
                ar4493
                10.1186/ar4493
                3978832
                25164150
                cffd0001-ed7f-4207-989e-f7cb482be4a2
                Copyright © 2014 Xie et al.; licensee BioMed Central Ltd.

                The licensee has exclusive rights to distribute this article, in any medium, for 6 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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