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      VEGF-attenuated platelet-rich plasma improves therapeutic effect on cartilage repair

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          Abstract

          VEGF-mediated angiogenesis inhibits cartilage repair. Here we used VEGF-binding microspheres to sequester VEGF out of PRP and generate VEGF-attenuated PRP, which improved the therapeutic effects of PRP in articular cartilage repair.

          Abstract

          Autologous platelet-rich plasma (PRP) has gained popularity as a less invasive treatment for various musculoskeletal tissue injuries and conditions due to its favorable safety profile, minimal manipulation and cost-effectiveness. Although PRP treatment has been clinically used for the treatment of osteoarthritis (OA) and damaged cartilage, evidence on therapeutic efficacy has been inconsistent, which calls for a methodology to achieve consistent and improved treatment outcomes. Given that PRP contains numerous proteins, we hypothesized that attenuation of a growth factor known to be detrimental to the healing tissue would enhance efficacy of PRP treatment. Considering that VEGF-mediated angiogenesis inhibits the repair of articular cartilage, we developed VEGF-attenuated PRP by sequestering VEGF in PRP using VEGF-binding microspheres. We demonstrated that VEGF attenuation in PRP did not inhibit the effect of PRP on chondrogenic differentiation of stem cells in vitro. In addition, healing of rat OA cartilage was significantly improved after treatment with VEGF-attenuated PRP when compared to the PRP treatment group or PBS control group. We expect that attenuation of unwanted biological activity using growth factor-binding microspheres could provide a new PRP customization method broadly applicable to various tissue repair processes.

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          Most cited references53

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          Osteoarthritis cartilage histopathology: grading and staging.

          Current osteoarthritis (OA) histopathology assessment methods have difficulties in their utility for early disease, as well as their reproducibility and validity. Our objective was to devise a more useful method to assess OA histopathology that would have wide application for clinical and experimental OA assessment and would become recognized as the standard method. An OARSI Working Group deliberated on principles, standards and features for an OA cartilage pathology assessment system. Using current knowledge of the pathophysiology of OA morphologic features, a proposed system was presented at OARSI 2000. Subsequently, this was widely circulated for comments amongst experts in OA pathology. An OA cartilage pathology assessment system based on six grades, which reflect depth of the lesion and four stages reflecting extent of OA over the joint surface was developed. The OARSI cartilage OA histopathology grading system appears consistent and simple to apply. Further studies are required to confirm the system's utility.
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            OARSI guidelines for the non-surgical management of knee osteoarthritis.

            To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide. Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores. Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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              Platelet-rich plasma: from basic science to clinical applications.

              Platelet-rich plasma (PRP) has been utilized in surgery for 2 decades; there has been a recent interest in the use of PRP for the treatment of sports-related injuries. PRP contains growth factors and bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article examines the basic science of PRP, and it describes the current clinical applications in sports medicine. This study reviews and evaluates the human studies that have been published in the orthopaedic surgery and sports medicine literature. The use of PRP in amateur and professional sports is reviewed, and the regulation of PRP by antidoping agencies is discussed.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                BSICCH
                Biomaterials Science
                Biomater. Sci.
                Royal Society of Chemistry (RSC)
                2047-4830
                2047-4849
                May 04 2022
                2022
                : 10
                : 9
                : 2172-2181
                Affiliations
                [1 ]Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA
                [2 ]Linda & Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO, USA
                [3 ]Department of Orthopedic Surgery, University of Texas Health Science Center at Houston, Houston, TX, USA
                [4 ]Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA
                [5 ]Materials Science Program, University of Wisconsin-Madison, Madison, WI, USA
                Article
                10.1039/D1BM01873F
                9622215
                35348136
                b9efb8a5-2fbb-4729-8fbe-272c6af6515d
                © 2022

                http://rsc.li/journals-terms-of-use

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