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      Development and Prospect of Intra-Articular Injection in the Treatment of Osteoarthritis: A Review

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          Abstract

          Osteoarthritis (OA) is a common degenerative disease that affects the vast majority of the elderly and may eventually embark on the road of the total knee arthroplasty (TKA), although controversy still exists in the medical community about the best therapies for osteoarthritis. Compared with physical therapy, oral analgesics and other non-operative treatments, intra-articular injection is more safe and effective. Moreover, intra-articular injection is much less invasive and has fewer adverse reactions than surgical treatment. This article reviews mechanism, benefits and adverse reactions of corticosteroids (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), mesenchymal stem cell (MSCs), stromal vascular fraction (SVF) and other new therapies (for example: gene therapy). The application prospect of intra-articular injection was analyzed according to the recent progress in drug research.

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          Most cited references 101

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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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            Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial.

            : Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 10(6) cells), medium dose (10 × 10(6)), and high dose (50 × 10(6)). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy.
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              Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis.

              The aim of the study was to determine if isolated mesenchymal stem cells (MSCs) derived from the infrapatellar fat pad could effectively improve clinical results when percutaneously injected into arthritic knees. Therapeutic case-control study; Level III. Twenty five stem cell injections combined with arthroscopic debridement were administered to patients with knee OA. A mean of 1.89 × 10(6) stem cells were prepared with approximately 3.0 mL of platelet-rich plasma (PRP) and injected in the selected knees of patients in the study group. The mean Lysholm, Tegner activity scale, and VAS scores of patients in the study group improved significantly by the last follow-up visit. No major adverse events related to the injections were observed during the treatment and follow-up periods. The results were compared between the study and control groups, in which the patients had undergone arthroscopic debridement and PRP injection without stem cells. Although the preoperative mean Lysholm, Tegner activity scale, and VAS scores of the study group were significantly poorer than those of the control group, the clinical results at the last follow-up visit were similar and not significantly different between the two groups. The short-term results of our study are encouraging and demonstrate that infrapatellar fat pad-derived MSC therapy with intraarticular injections is safe, and provides assistance in reducing pain and improving function in patients with knee OA. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                04 August 2020
                2020
                : 13
                : 1941-1955
                Affiliations
                [1 ]Department of Orthopedic Surgery, Zhejiang Provincial People’s Hospital and People’s Hospital of Hangzhou Medical College , Hangzhou, Zhejiang 310014, People’s Republic of China
                [2 ]The First Affiliated Hospital of Bengbu Medical University , Bengbu, Anhui 233004, People’s Republic of China
                [3 ]The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325000, People’s Republic of China
                Author notes
                Correspondence: Qing Bi Department of Orthopedic Surgery, Zhejiang Provincial People’s Hospital , No. 158 Shangtang Road, Hangzhou, Zhejiang, People’s Republic of China Email bqzjsrmyy@163.com
                Article
                260878
                10.2147/JPR.S260878
                7414982
                © 2020 Zhang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 3, Tables: 5, References: 130, Pages: 15
                Categories
                Review

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