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  • Cartilage Regeneration: How Do We Meet the Increasing Demands of an Ageing Population?

    Editorial

    Globally, hundreds of millions of people are affected by musculoskeletal disorders (~10 million in the UK) [1]. Data presented from a pan-European study showed that one in three people are affected by musculoskeletal pain and disorders of the musculoskeletal system are the most common work-related health problem. From a survey of individuals who retired early on medical grounds or were on long-term sickness benefit, up to 60% cited musculoskeletal pain as the cause [2]. As well as these societal implications there is a significant economic cost associated with musculoskeletal health. The National Health Service (NHS) spends over

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  • Efficacy and safety profile of a compound composed of platelet-rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results)

    Abstract

    Background

    The combined use of hyaluronic acid and platelet-rich plasma has never been reported in the treatment for osteoarthritis. Aim of this paper was to evaluate the efficacy of this association and to compare retrospectively these results with those of a cohort of patients treated with platelet-rich plasma only.

    Materials and methods

    Subjects with mild-to-moderate knee osteoarthritis were enrolled. After clinical and ultrasound evaluation, patients received a weekly intra-articular injection of 2

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  • Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee

    Abstract

    Purpose

    To compare the clinical outcomes of osteoarthritis indices (WOMAC and Lequesne scores) and adverse events in the treatment of osteoarthritis (OA) of the knee with platelet-rich plasma (PRP) versus hyaluronic acid (HA) or placebo.

    Methods

    A systematic review and meta-regression were performed to compare outcomes between PRP injections versus HA or placebo. Relevant randomized control trials were identified from Medline and Scopus from date of inception to 13 August 2015.

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  • RANTES and SDF-1 Are Keys in Cell-based Therapy of TMJ Osteoarthritis

    Abstract

    The present study aimed to investigate the therapeutic effect of injections of local bone marrow mesenchymal stem cells (BMSCs) on osteoarthritis (OA) of the temporomandibular joint (TMJ) and to explore the role of stromal cell-derived factor 1 (SDF-1) and regulated on activation, normal T-cell expressed and secreted (RANTES) in this effect. Fundamentally, OA of the TMJ was induced by unilateral anterior crossbite in mice. Exogenous green fluorescent protein-labeled BMSCs (GFP-BMSCs) were weekly injected into the TMJ region for 4, 8, and 12 wk. The reparative effects of exogenous GFP-BMSCs were investigated by morphological observation and micro-computed tomography. The differentiation of GFP-BMSCs in the cartilage was examined by double immunofluorescence of GFPs with type II collagen, and the expression of related factors in the condylar cartilage was quantified by real-time polymerase chain reaction. The role of RANTES and SDF-1 in the therapeutic effect of exogenous BMSCs was examined by both in vitro and in vivo studies. The OA cartilage of the TMJ displays a synchronous increase in SDF-1 and RANTES expression and a higher capability of attracting the migration of GFP-BMSCs. The implanted GFP-BMSCs differentiated into type II collagen-positive cells and reversed cartilage degradation and subchondral bone loss in mice with OA of the TMJ. The migration of GFP-BMSCs towards OA cartilage and the rescuing effect of GFP-BMSC injections were impaired by the inhibitors of C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 1 (CCR1), which are the receptors of SDF-1 and RANTES, respectively. Our data indicated that SDF-1/CXCR4 and RANTES/CCR1 signals are pivotal and function synergistically in the recruitment of GFP-BMSCs towards degraded cartilage in mice OA of the TMJ.

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  • A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis

    Abstract

    Background

    Prior studies describing the treatment of symptomatic knee osteoarthritis with injections of bone marrow concentrate have provided encouraging results. The relationship between the cellular dose contained within the bone marrow concentrate and efficacy of the treatment, however, is unclear. In the present study we describe clinical outcomes for symptomatic knee osteoarthritis in relation to higher and lower cell concentrations contained within a bone marrow concentrate treatment protocol.

    Methods

    Data from an ongoing patient registry was culled to identify 373 patients that received bone marrow concentrate injections for the treatment of 424 osteoarthritic knee joints. The clinical scales for these patients were assessed at baseline and then tracked post-procedure at 1, 3, 6 and 12

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  • Mesenchymal Stem Cells in Regenerative Medicine: Focus on Articular Cartilage and Intervertebral Disc Regeneration

    Abstract

    Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.

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  • Sonographically guided obturator internus injections: techniques and validation

    Abstract

    OBJECTIVES: The primary purpose of this investigation was to describe and validate sonographically guided techniques for injecting the obturator internus (OI) muscle or bursa using a cadaveric model.

    METHODS: A single experienced operator completed 10 sonographically guided OI injections in 5 unembalmed cadaveric pelvis specimens (4 female and 1 male, ages 71-89 years with body mass indices of 15.5-24.2 kg/m2). Four different techniques were used: (1) OI tendon sheath (4 injections), (2) OI intramuscular (2 injections), (3) OI bursa trans-tendinous (2 injections), and (4) OI bursa short-axis (2 injections). In each case, the operator injected 1.5 mL of diluted yellow latex using direct sonographic guidance and a 22-gauge, 87.5-mm (3

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  • Effectiveness of a single platelet-rich plasma injection to promote recovery in rugby players with ankle syndesmosis injury

    Abstract

    Aims To determine whether a single ultrasound-guided platelet-rich plasma (PRP) injection into the anterior inferior tibiofibular ligament (AITFL) reduces the time for rugby athletes to return to function and match play following MRI confirmed ankle syndesmosis injury.

    Methods Cohort controlled pilot study. 10 Rugby Union players were recruited during the 2014 season, and consented to receive a single autologous PRP injection into the AITFL within 14 €…days of MRI confirmed ankle syndesmosis injury. A historical control group included 11 comparable Rugby Union players between 2011 and 2013 who were treated conservatively with the same inclusion criteria and rehabilitation protocol as the intervention group. Participants followed a standardised rehabilitation protocol involving simple milestones for progression. Early functional tests were performed 2 €…weeks after the removal of the CAM (controlled ankle motion) boot. Time to return to play was recorded. Repeat functional testing occurred within 1 €…week of return to play.

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  • Intraarticular Injection of Allogenic Mesenchymal Stem Cells has a Protective Role for the Osteoarthritis

    Background:

    Researchers initially proposed the substitution of apoptotic chondrocytes in the superficial cartilage by injecting mesenchymal stem cells (MSCs) intraarticularly. This effect was termed as bio-resurfacing. Little evidence supporting the treatment of osteoarthritis (OA) by the delivery of a MSC suspension exists. The aim of this study was to investigate the effects of injecting allogenic MSCs intraarticularly in a rat OA model and to evaluate the influence of immobility on the effects of this treatment.

    Methods: We established a rat knee OA model after 4 and 6 weeks and cultured primary bone marrow MSCs. A MSC suspension was injected into the articular space once per week for 3 weeks. A subgroup of knee joints was immobilized for 3 days after each injection, while the remaining joints were nonimmobilized. We used toluidine blue staining, Mankin scores, and TdT-mediated dUTP-biotin nick end labeling staining to evaluate the therapeutic effect of the injections. Comparisons between the therapy side and the control side of the knee joint were made using paired t-test, and comparisons between the immobilized and nonimmobilized subgroups were made using the unpaired t-test. A P value < 0.05 was considered significant.

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  • Intramuscular oxygen-ozone therapy in the treatment of acute back pain with lumbar disc herniation: a multicenter, randomized, double-blind, clinical trial of active and simulated lumbar paravertebral injection

    Abstract

    STUDY DESIGN: Multicenter randomized, double-blind, simulated therapy-controlled trial in a cohort of patients with acute low back pain (LBP) due to lumbar disc herniation (LDH).

    OBJECTIVE: To assess the benefit of intramuscular-paravertebral injections of an oxygen-ozone (O2O3) mixture.

    SUMMARY OF BACKGROUND DATA: Recent findings have shown that O2O3 therapy can be used to treat LDH that fails to respond to conservative management. However, these findings are based on intradiscal/intraforaminal O2O3 injection, whereas intramuscular-paravertebral injection is the technique used most in clinical practice in Italy and other Western countries.

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  • Platelet-rich plasma for chronic lateral epicondylitis: Is one injection sufficient?

    Abstract

    Introduction

    Chronic lateral epicondylitis is generally treated using nonsurgical methods including physiotherapy and infiltrations of cortisone or platelet-rich plasma (PRP). The latter is known for its simple application as well as associated low risk of adverse events, which lend to its widespread use in treating various musculoskeletal conditions. There is limited evidence on the effectiveness of PRP injections to optimally treat chronic lateral epicondylitis. This study explored the effectiveness of single or repeated injections for patients with symptoms that spanned 6 months or more and were unresponsive to alternate conservative measures.

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  • Platelet-Rich Plasma Injection for Symptomatic Knee Osteoarthritis

    Abstract

    Background: Platelet-rich plasma (PRP) is plasma of enriched platelets with high concentration of platelet granules and growth factors. The platelet growth factors have a great potential of wound and connective tissue healing used to treat cartilage lesions and retarding the progression of knee osteoarthritis

    .

    Objectives: This study was designed to evaluate PRP injection results in knee osteoarthritis.

    Patients and Methods: This was a case-series study of 39 patients and all of them had three injections of PRP for the involved knee (every two weeks) and they were followed up at two weeks, two months and six months post-injection of PRP. All included patients filled the WOMAC (western Ontario and Mcmaster universities arthritis index) standardized and translated to our national language and culture. We analyzed the collected scores of before initiation of PRP injections, the second week, the second month and the sixth month after injections into the knees.

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  • Stem cells in orthopaedics

    Abstract

    Sharing new ideas and approaches is needed to advance basic scientific research as well as the clinical application of stem cells. In this newsletter we present the current knowledge in stem cell research and therapy within the field of orthopaedics, presenting the definitions, types and sources of the stem cells. The second part of this newsletter focuses on the clinical application of stem cells in the therapy of tissues with very limited capacity for self-regeneration; this includes tendons and ligaments, particularly found in rotator cuff rupture. The sever problems associated with articular cartilage repair have lead to the need for the development of clinical research, with the aim of finding efficient clinical applications of stem cell therapy in cartilage defects and osteoarthritis. However in addition to this, such therapy could be used for the regeneration of bone, as in bone defect repair. The clinical outcome of stem cell therapy is a promising option for the treatment of cartilage, bone and tendon defects; however an increased sample size and additional long-term prospective randomised studies are needed to confirm these preliminary results.

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  • Characteristics of canine platelet-rich plasma prepared with five commercially available systems

    OBJECTIVE To characterize platelet-rich plasma (PRP) products obtained from canine blood by use of a variety of commercially available devices.

    SAMPLE Blood samples from 15 dogs between 18 months and 9 years of age with no concurrent disease, except for osteoarthritis in some dogs.

    PROCEDURES PRP products were produced from blood obtained from each of the 15 dogs by use of each of 5 commercially available PRP-concentrating systems. Complete blood counts were performed on each whole blood sample and PRP product. The degree of platelet, leukocyte, and erythrocyte concentration or reduction for PRP, compared with results for the whole blood sample, was quantified for each dog and summarized for each concentrating system.

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  • Management of a One-wall Intrabony Osseous Defect with Combination of Platelet Rich Plasma and Demineralized BoneMatrix- a Two-year Follow up Case Report

    Abstract

    Periodontal regeneration in a one-wall intrabony defect is a challenging and complex phenomenon. The combination therapy of commercially available bone grafts with the innovative tissue engineering strategy, the platelet rich plasma, has emerged as a promising grafting modality for two and three walled intrabony osseous defects. The application of this combination approach was attempted in a most challenging one-wall intrabony defect. Open flap debridement and placement ofcombination of autologous platelet rich plasma(PRP) and demineralized bone matrix was done in one-wall intrabony defect in relation to tooth #21 in a 30 yearold female patient. The 6-month follow- up results showed significant improvement in clinical parameters. Radiographic evidence of bone formation was observedas early as 3 months with almost complete fill by 6 months postoperatively. The results were maintained over a period of 2 years.

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  • Platelet rich plasma versus corticosteroid injection for plantar fasciitis: A comparative study

    Abstract

    Introduction

    Intractable plantar fasciitis can be a difficult condition to treat. Early results of platelet rich plasma (PRP) injection have been promising. We compared PRP to traditional cortisone injection in the treatment of chronic cases of plantar fasciitis resistant to traditional nonoperative management. The aim of the study was to compare the efficacy of PRP to that of Steroid at 3, 6 and 12 months after injection.

    Methods

    60 heels with intractable plantar fasciitis who had failed conservative treatment were randomized to receive either PRP or Steroid injection. All patients were assessed with the Roles-Maudsley (RM) Score, Visual Analogue Score (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Data was collected prospectively on the cohort, pre-treatment, at 3, 6 and 12 months post injection and the results were compared.

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  • Dextrose Prolotherapy versus Control Injections in Painful Rotator Cuff Tendinopathy

    Abstract

    Objective

    To compare the effect of dextrose prolotherapy on pain levels and degenerative changes in painful rotator cuff tendinopathy against two potentially active control injection procedures.

    Design

    Randomized controlled trial, blinded to participants and evaluators.

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  • Platelet-Rich Plasma May Improve Osteochondral Donor Site Healing in a Rabbit Model

    Abstract

    Purpose. The purpose of this study was to assess the effect(s) of platelet-rich plasma (PRP) on osteochondral donor site healing in a rabbit model. Methods. Osteochondral donor sites 3 mm in diameter and 5 mm in depth were created bilaterally on the femoral condyles of 12 New Zealand White rabbits. Knees were randomized such that one knee in each rabbit received an intra-articular injection of PRP and the other received saline (placebo). Rabbits were euthanized at 3, 6, and 12 weeks following surgery. Repair tissue was evaluated using the International Cartilage Repair Society (ICRS) macroscopic and histological scores. Results. No complications occurred as a result of the interventions. There was no significant difference in macroscopic scores between the 2 groups (5.5

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  • Researchers report good first results using blood stem cells, HA to regenerate cartilage

    Scientific investigators from Malaysia reported the first evidence of hyaline cartilage regeneration using intra-articular injections of autologous peripheral blood stem cells in combination with hyaluronic acid.

    In their clinical trial, researchers from the Kuala Lumpur Sports Medicine Centre and the University Putra Malaysia followed 10 patients with full-thickness chondral defects treated with arthroscopic multiple subchondral drilling. The investigators followed the patients for a minimum of 2 years.

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  • Pluripotent Stem Cells and Skeletal Regeneration —Promise and Potential

    Abstract

    The bone is a regenerative tissue, capable of healing itself after fractures. However, some circumstances such as critical-size defects, malformations, and tumor destruction may exceed the skeleton's capacity for self-repair. In addition, bone mass and strength decline with age, leading to an increase in fragility fractures. Therefore, the ability to generate large numbers of patient-specific osteoblasts would have enormous clinical implications for the treatment of skeletal defects and diseases. This review will highlight recent advances in the derivation of pluripotent stem cells, and in their directed differentiation towards bone-forming osteoblasts.

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