General

  • Intratendinous Injection of Platelet-Rich Plasma under US Guidance toTreat Tendinopathy:A Long- Term Pilot Study

    Abstract

    Purpose: To assess the potential therapeutic effect of intratendinous injection of platelet-richplasma(PRP) under ultrasound (US) guidance to treat tendon tears and tendinosis in a pilot study with long-term follow-up.

    Materials and Methods: The study included 408 consecutive patients referred fort reatment by PRP in jection of tendinopathy in the upper (medial and lateral epicondylar tendons)and the lower(patellar,Achilles,hamstring and adductor longus,and peroneal tendons)limb who received a single intra tendinous injection of PRP under US guidance. Clinical and US data were retrospectively collected for each anatomic compartment for upper and lower limbs before treatment(baseline)and 6 weeks after treatment. Late clinical data without US were collected until 32 months after the procedure(mean,20.2months). The McNemar test and regression model were used to compare clinical and US data.

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  • Platelet-rich Plasma as an Effective Treatment for Proximal Hamstring Injuries

    Abstract

    Proximal hamstring injuries can be disabling, and several traditional conservative treatments, including physiotherapy and nonsteroidal anti-inflammatory drugs, have been inconsistent. Corticosteroid injections have demonstrated success but can adversely affect local tissues. Platelet-rich plasma (PRP) has emerged as a safe, effective treatment for several orthopedic pathologies. The authors propose a PRP injection at the muscle origin as a novel treatment for proximal hamstring injuries.

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  • Ultrasound-guided platelet-rich plasma injection for distal biceps tendinopathy

    Abstract

    Background Distal biceps tendinopathy is an uncommon cause of elbow pain. The optimum treatment for cases refractory to conservative treatment is unclear. Platelet-rich plasma has been used successfully for other tendinopathies around the elbow.

    Methods Six patients with clinical and radiological evidence of distal biceps tendinopathy underwent ultrasound-guided platelet-rich plasma (PRP) injection. Clinical examination findings, visual analogue score (VAS) for pain and Mayo Elbow Performance scores were recorded.

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  • Case-control study on local injection of autoallergic platelet rich plasma or whole blood for the treatment of tennis elbow

    Abstract

    OBJECTIVE: To compare therapeutic effects of local injection with autoallergic platelet rich plasma (PRP) or autoallergic whole blood (AWB) for the treatment of chronic tennis elbow.

    METHODS: From January 2011 to January 2014, 40 patients with chronic tennis elbow were divided into 2 groups, 20 cases in each group: PRP group and AWB group. There were 20 patients in PRP group treated with local injection of autoallergic platelet rich plasma, including 5 males and 15 females, with an average age of (47.50

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  • Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib

    Abstract

    Objectives To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.

    Methods

    Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.

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  • Intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis

    Abstract

    BACKGROUND: Rheumatoid arthritis (RA) is a debilitating and painful disease leading to increased morbidity and mortality and novel therapeutic approaches are needed. The purpose of this study was to elucidate if mesenchymal stem cells (MSCs) injected in the joints of mice with arthritis are therapeutic, reducing joint swelling and cartilage destruction.

    METHODS: Murine mesenchymal stem cells (mMSCs) were isolated from bone marrow of C57Bl/6 mice and expanded in culture. Cells were tested for immunophenotype and their ability to form colonies and to differentiate into chondrocytes, osteocytes and adipocytes. Antigen-induced arthritis (AIA) was induced by intra-articular injection of methylated bovine serum albumin into the knee joints of preimmunized C57Bl/6 mice. After one day, when peak swelling occurs, 500,000 mMSCs labelled with red fluorescent cell tracker CM-DiI were injected intra-articularly in the right knee joint. Left knee joints were treated as controls by receiving PBS injections. Differences between groups were calculated by Mann Whitney U test or unpaired t tests using GraphPad Prism software version 5.

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  • In situ recruitment of human BMSCs using chemokines for articular cartilage regeneration

    Abstract

    Bone marrow-derived mesenchymal stem cells (BMSCs) are a good cell source for regeneration of cartilage as they can migrate directly to the site of cartilage injury and differentiate into articular chondrocytes. Articular cartilage defects do not heal completely due to the lack of chondrocytes or BMSCs at the site of injury. In this study, the chemotaxis of BMSCs toward chemokines, which may give rise to a complete regeneration of the articular cartilage, was investigated. CCR2, CCR4, CCR6, CXCR1, and CXCR2 were expressed in normal BMSCs and were increased significantly upon treatment with pro-inflammatory cytokines. BMSC migration was increased by MIP-3a and IL-8 more than by MCP-1 or SDF-1?. IL-8 and MIP-3? significantly enhanced the chemotaxis of BMSCs compared with MCP-1, SDF-1?, or the PBS. Human BMSC recruitment to transplanted scaffolds containing either IL-8 or MIP-3? significantly increased in vivo compared with that to scaffolds containing the PBS. Furthermore, IL-8- and MIP-3?-containing scaffolds enhanced tissue regeneration of ostechondral defect site formed in beagle knee articular cartilage. Therefore, this study suggests that IL-8 and MIP-3? are the candidates that induce the regeneration of damaged articular cartilage.

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  • Surgery for persistent knee pain? Not so fast

    Illustrative case

    A 40-year-old man comes to your office for follow-up of medial left knee pain he\'s had for 3 months that hasn\'t responded to conservative treatment. The pain developed gradually, without a history of trauma. The patient has no signs of degenerative joint disease on x-ray but magnetic resonance imaging (MRI) reveals a tear of the medial meniscus. Should you refer him for meniscectomy?

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  • Stromal cells and stem cells in clinical bone regeneration

    Abstract

    Stem-cell-mediated bone repair has been used in clinical trials for the regeneration of large craniomaxillofacial defects, to slow the process of bone degeneration in patients with osteonecrosis of the femoral head and for prophylactic treatment of distal tibial fractures. Successful regenerative outcomes in these investigations have provided a solid foundation for wider use of stromal cells in skeletal repair therapy. However, employing stromal cells to facilitate or enhance bone repair is far from being adopted into clinical practice. Scientific, technical, practical and regulatory obstacles prevent the widespread therapeutic use of stromal cells. Ironically, one of the major challenges lies in the limited understanding of the mechanisms via which transplanted cells mediate regeneration. Animal models have been used to provide insight, but these models largely fail to reproduce the nuances of human diseases and bone defects. Consequently, the development of targeted approaches to optimize cell-mediated outcomes is difficult. In this Review, we highlight the successes and challenges reported in several clinical trials that involved the use of bone-marrow-derived mesenchymal or adipose-tissue-derived stromal cells. We identify several obstacles blocking the mainstream use of stromal cells to enhance skeletal repair and highlight technological innovations or areas in which novel techniques might be particularly fruitful in continuing to advance the field of skeletal regenerative medicine.

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  • Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis

    Abstract

    Objectives: To determine and compare the effects of autologous platelet rich plasma (PRP) and hyaluronic acid (HA) for the treatment of osteoarthritis of the knee.

    Methods: This prospective study included 150 patients affected by severe osteoarthritis of the knee. Gonarthrosis was graded using the Kellgren-Lawrence and Albhack radiographic classification scale. 150 patients were randomized into 2 study groups .In the PRP group (n=55) three intraarticular injection were applied andthe control group (n=55) received 3 intra-articular injections of high molecular weight HA. An unblinded physician performed infiltration once a week for 3 weeks into the knee affected by clinically relevant gonarthrosis (in both groups). All patients were evaluated with the Western Ontario and McMaster (WOMAC) score and visual pain scale before the infiltration and at 3, 6, and 12 months after the first injection.

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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

    Abstract

    Objective. To compare the outcome of matrix-induced autologous chondrocyte implantation (MACI) and bone marrow aspirate concentrate (BMAC)-derived multipotent stem cells (MSCs) implantation in patellofemoral chondral lesions, using the same HYAFF11 scaffold. Methods. From January 2005 to December 2010, 37 patients with patellofemoral chondral lesions were prospectively followed up, for a minimum of 3 years; 19 of these patients were treated with MACI and 18 with BMAC. Radiographs, magnetic resonance imaging, and clinical scores (International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, visual analog scale, and Tegner) were collected preoperatively, at 2-year and final follow-up. Five patients of MACI and 6 of the BMAC group underwent second-look arthroscopy; 4 patients of each group consented to a concomitant biopsy. Results. No adverse reactions or postoperative infections were noted. Baseline characteristics were similar in both groups (P > 0.05). Both groups showed significant improvement in all scores, from preoperative to final follow-up (P = 0.001), but there was no significant difference in improvement between the 2 groups, except for the IKDC subjective score (P = 0.015), which favored the BMAC group. Deterioration in MACI and improvement in BMAC group scores were noticed, from 2-year to final follow-up, but was nonsignificant. MACI patients with trochlear lesions showed better results than patellar lesions, while location was not a prognostic factor in the BMAC group. MRI showed complete filling of the defects in 76% of patients in MACI and 81% of patients in BMAC, and histological analysis revealed hyaline-like features. Conclusion. Both techniques are viable and effective for large patellofemoral chondral lesions at minimum 3-year follow-up.

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  • Mesenchymal Stem Cells and Cartilage Regeneration in Traumatic and OsteoarthriticCartilage Defects

    Abstract

    Osteoarthritis (OA) affects several hundred million people and is one of the leading causes of disability around the world. Aging is the most influential risk factor for developing OA. Cartilage has a limited ability to spontaneously heal; therefore, it needs surgical intervention in case of cartilage defects caused by traumatic injury or degenerative disease. Due to the shortage of autologous chondrocytes and autografts that require additional defects, adult human mesenchymal stem cells (MSCs), the precursors of chondrocytes, become possible options for cartilage regeneration in traumatic and Osteoarthritic cartilage defects.

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  • The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee

    Abstract

    Purpose To assess the outcome of intra-articular plateletrich plasma (PRP) injections into the knee in patients with early stages of osteoarthritis (OA) and to determine whether cyclical dosing would affect the end result. Methods This is a prospective, randomized study in which 93 patients (119 knees) were followed up for a minimum of 2 years. Fifty knees were randomly selected prior to the first injection, to receive a second cycle at the completion of 1 year. A cycle consisted of three injections, each given at a monthly interval. The outcome was assessed using Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Scale (VAS), Tegner and Marx scoring systems, recorded prior to the first injection and then at 12, 18 and 24 months.

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  • Tendon Derived Stem Cells Promote Platelet-Rich Plasma Healing in Collagenase-Induced Rat Achilles Tendinopathy

    Abstract

    Background/Aims: Tendon injuries are common, difficult to cure and usually healed with fibrosis and scar tissue. The aim of this study was to evaluate tendon derived stem cells (TDSCs) and platelet rich plasma (PRP) in the treatment of collagenase induced Achilles tendinopathy in rat. Methods: Four and 8 weeks (n=18) after TDSCs, PRP, PRP with TDSC or PBS (control) injection into collagenase or saline (sham) injected rat Achilles tendon, tendon tissue was harvested and tendon quality was evaluated by histology and biomechanical testing. TDSCs were cultured and treated by 10% PRP, and the FAK/ERK1/2 signaling pathway and tenocyte-related genes were detected by western blot analysis. Results: Compared to the control, PRP treatment resulted in better healing of injured tendons with improved histological outcomes and biomechanical functions. The addition of TDSCs to PRP treatment significantly enhanced the effects of PRP treatment alone. TDSC injection alone had little effect on tendon healing. PRP and PRP with TDSC treatments of collagenase induced tendon injuries also increased the mRNA and protein expression of tenocyte-related genes (type I collagen, SCX, Tenascin C) and activated the focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) 1/2 signaling pathways. Treatment of TDSCs in vitro with 10% PRP significantly increased the phosphorylation levels of FAK and ERK1/2 and the protein levels of tenocyte-related genes (Col I, SCX and Tenascin C). Inhibition of the FAK and ERK1/2 signaling pathways abolished the effect of PRP. Conclusion: This study concludes that PRP combined with TDSCs is potentially effective for the treatment of tendinopathy. The PRP induced, FAK and ERK1/2 dependent activation of tenocyte related genes in TDSCs in vitro suggests that the beneficial healing effect of the PRP with TDSC combination might occur by means of an improved TDSC differentiation toward the tenocyte lineage. Thus, a PRP with TDSC combination therapy may be clinically useful.

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  • Oxygen-ozone therapy for herniated lumbar disc in patients with subacute partial motor weakness due to nerve root compression

    Abstract

    Intradiscal oxygen-ozone (O2-O3) chemonucleolysis is a well-known effective treatment for pain caused by protruding disc disease and nerve root compression due to bulging or herniated disc. The most widely used therapeutic combination is intradiscal injection of an O2-O3 mixture (chemonucleolysis), followed by periradicular injection of O2-O3, steroid and local anaesthetic to enhance the anti-inflammatory and analgesic effect. The treatment is designed to resolve pain and is administered to patients without motor weakness, whereas patients with acute paralysis caused by nerve root compression undergo surgery 24-48h after the onset of neurological deficit. This paper reports on the efficacy of O2-O3 chemonucleolysis associated with anti-inflammatory foraminal injection in 13 patients with low back pain and cruralgia, low back pain and sciatica and subacute partial motor weakness caused by nerve root compression unresponsive to medical treatment. All patients were managed in conjunction with our colleagues in the Neurosurgery Unit of Bellaria Hospital and the IRCCS Institute of Neurological Sciences, Bologna. The outcomes obtained are promising: 100% patients had a resolution of motor weakness, while 84.6% had complete pain relief. Our results demonstrate that O2-O3 therapy can be considered a valid treatment option for this category of patients.

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  • Single injection of platelet-rich plasma (PRP) for the treatment of refractory distal biceps tendonitis: long-term results of a prospective multicenter cohort study

    Abstract

    Purpose

    There is a lack of evidence regarding the use of PRP in the treatment of distal biceps tendonitis. The purpose of this study was to assess the effectiveness of ultrasound (US)-guided injection of PRP in relieving pain and functional impairment in the treatment of refractory distal biceps tendonitis.

    Methods

    Twelve patients from two large tertiary referral hospitals were recruited over a period of 20

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  • Single Dose of Intra-Muscular Platlet Rich Plasma Reverses the Increase in Plasma Iron Levels in Exercise Induced Muscle Damage

    Abstract

    Objectives: Autologous Platelet Rich Plasma (PRP) therapy, is considered to be a promising solution in accelerating the healing process of injured skeletal muscle tissue. In addition to the release of growth factors, PRP also promotes concentrated anti-inflammatory signals, including interleukins. However, the impact of the intramuscular administration of the PRP on hematologic and biochemical responses has not been fully elucidated in exercise induced muscle damage.

    Methods: Twelve healthy moderately active male volunteers, without previous experience with eccentric/concentric elbow flexors exercise, participated in this study. They were divided into two groups: control group (CONTROL, n=6) and platelet rich plasma administration group (PRP, n=6) group. To induce muscle damage, subjects in both groups performed concentric/eccentric contractions with load of (80 % 1RM) maximal voluntary contraction of the elbow flexors until point of exhaustion of the non-dominant arm. The non-dominant arms of the PRP group were treated with autologous PRP (Regen ACR-C, Regen Lab, Switzerland) post-24h exercise induced damage (DOMS). Subsequently, 4 ml PRP samples was injected using a 20-gauge needle into the region of the biceps brachii of the non-dominant arm under sterile aseptic conditions. Venous blood samples were collected pre-, and 4 days post-exercise, and analyzed for complete blood counts, serum ferritin, iron, iron binding capacity (IBC), creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) as markers of muscle damage and inflammation.

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  • Fibroblast Growth Factor 18 Increases the Trophic Effects of Bone Marrow Mesenchymal Stem Cells on Chondrocytes Isolated from Late Stage Osteoarthritic Patients

    1. Introduction

    Osteoarthritis (OA) is known as the most common degenerative diseases in joints. Symptoms of OA include a group of mechanical abnormalities, which reflect the degradationof articular cartilage and the corresponding subchondral bones [1]. OA patients normally experience pain, tenderness, stiffness, locking, and/or effusion of joints. A lot of factorsincluding genetics, developmental environment,metabolism, and mechanical injury are considered as causes for initiating degradation of cartilage. Once started, cartilage tissue willbecome thinner and thinner; then bony surfaces of joints will be protected and buffer less and less. Then subchondral bone may be damaged. As the most common type of arthritis, to be an anabolic factor on chondrocytes in articular cartilage [10]. It has also been reported that FGF18 may accelerate the biosynthesis of type II collagen synthesis and extracellular matrix deposition of chondrocytes [11]. Based on these reports as well as the fact that injection of rhFGF18 prevented cartilage degeneration in rat osteoarthritis models, FGF18 is believed to protect articular cartilage from intra-articular injury [12]. Furthermore, beneficial effects of FGF18 have also been shown in the repair of damaged cartilage in a rat study of injury-induced osteoarthritis, conducted by Moore et al. [13].

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  • Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration

    Abstract

    The aims of this study were to (1) determine whether platelet-rich plasma (PRP) could be prepared as a bioactive scaffold capable of endogenous growth factor release for cartilage repair; (2) compare the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) from bone marrow (BMSC) and from adipose (ADSC) seeded within the PRP scaffold; and (3) test the efficacy of ADSC-PRP construct in cartilage regeneration in

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  • Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis

    Abstract

    Background The effectiveness of platelet-rich plasma (PRP) injections for osteoarthritis (OA) is still controversial. We investigated the effect of PRP injections in patients with knee OA based on decreasing pain, improving function, global assessment and changes regarding joint imaging.

    Methods We performed a comprehensive, systematic literature search in computerised databases (MEDLINE, EMBASE, CINAHL, CENTRAL, Web of Science and PEDro) until June 2014 for randomised or non-randomised controlled trials. These were graded for risk of bias and a level of evidence was provided. If possible, meta-analysis was performed

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