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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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  • One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions Results at 2-Year Follow-up

    Abstract

    Objective: The purpose of our study was to determine the effectiveness of cartilage repair utilizing 1-step surgery with bone marrow aspirate concentrate (BMAC) and a collagen I/III matrix (Chondro-Gide, Geistlich, Wolhusen, Switzerland). Materials and Methods: We prospectively followed up for 2 years 15 patients (mean age, 48 years) who were operated for grade IV cartilage lesions of the knee. Six of the patients had multiple chondral lesions; the average size of the lesions was 9.2 cm2. All patients underwent a mini-arthrotomy and concomitant transplantation with BMAC covered with the collagen matrix. Coexisting pathologies were treated before or during the same surgery. X-rays and MRI were collected preoperatively and at 1 and 2 years\' follow-up. Visual analog scale (VAS), International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, Marx, SF-36 (physical/mental), and Tegner scores were collected preoperatively and at 6, 12, and 24 months\' follow-up. Four patients gave their consent for second-look arthroscopy and 3 of them for a concomitant biopsy. Results: Patients showed significant improvement in all scores at final follow-up (P < 0.005). Patients presenting single lesions and patients with small lesions showed higher improvement. MRI showed coverage of the lesion with hyaline-like tissue in all patients in accordance with clinical results. Hyaline-like histological findings were also reported for all the specimens analyzed. No adverse reactions or postoperative complications were noted. Conclusion: This study showed that 1-step surgery with BMAC and collagen I/III matrix could be a viable technique in the treatment of grade IV knee chondral lesions.

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  • Platelet-Rich Plasma Injections for the Treatment of Hamstring Injuries

    Abstract

    Background: A hamstring injury is one of the most common types of injury affecting athletes. Despite this, the optimal management of hamstring muscle injuries is not yet defined. The effect of autologous platelet-rich plasma (PRP) therapy on the recovery of hamstring injuries is unclear.

    Purpose: To investigate the effect of a single PRP injection in the treatment of grade 2 hamstring muscle injuries.

    Study Design: Randomized controlled trial; Level of evidence, 2.

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  • The use of platelet-rich plasma for the treatment of osteoarthritis

    Abstract

    Osteoarthritis (OA) is the most common cause of disability in the United States. With an aging population, its incidence is only likely to rise. Articular cartilage has a poor capacity to heal. The advent of regenerative medicine has heralded a new approach to early treatment of degenerative conditions such as osteoarthritis by focusing on regenerating damaged tissue rather than focusing on replacement. Platelet-rich plasma (PRP) is one such treatment that has received much recent attention and has been used particularly for tendon healing. Recent studies have focused on assessing its use on degenerative conditions such as OA. In this article, we review the evidence for the pathologic basis for the use of PRP in OA and also the clinical outcomes pertaining to its use. Finally, we also consider reasons for the inconsistent clinical success pertaining to its use.

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  • Orthobiologics: Is it a game changer in Regenerative Orthopaedics?

    In the past 20 years, the field of medicine has witnessed an unprecedented rate of scientific discovery and experiments for newer materials to promote healing and the regenerative capacity of the human tissues and the use of biologic tissues for this purpose have evoked special interest. The term \'Orthobiologic\' is actually a marketing term that comes from the device industry and implies that the addition of these bio-engineered products or extrinsic forces can positively influence or up-regulate healing of human tissue.

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  • Heparin-Conjugated Poly(Lactic-Co-Glycolic Acid) Nanospheres Enhance Large-Wound Healing by Delivering Growth Factors in Platelet-Rich Plasma

    Abstract

    Platelet-rich plasma (PRP) contains many growth factors that are involved in tissue regeneration processes. For successful tissue regeneration, protein growth factors require a delivery vehicle for long-term and sustained release to a defect site in order to maintain their bioactivity. Previously, we showed that heparin-conjugated poly(lactic-co-glycolic acid) nanospheres (HCPNs) can provide long-term delivery of growth factors with affinity for heparin. In this study, we hypothesize that treatment of a skin wound with a mixture of PRP and HCPNs would provide long-term delivery of several growth factors contained in PRP to promote the skin wound healing process with preservation of bioactivity. The release of platelet-derived growth factor-BB (PDGF-BB), contained in PRP, from HCPN with fibrin gel (FG) showed a prolonged release period versus a PRP mixture with FG alone (FG-PRP). Also, growth factors released from PRP with HCPN and FG showed sustained human dermal fibroblast growth for 12 days. Full-thickness skin wound treatment in mice with FG-HCPN-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 9 compared with treatment with FG-HCPN or FG-PRP. The enhanced wound healing using FG-HCPN-PRP may be due to the prolonged release not only of PDGF-BB but also of other growth factors in the PRP. The delivered growth factors accelerated angiogenesis at the wound site.

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  • Treatment of advanced stage gonarthrosis with prolotherapy: case report

    Abstract

    INTRODUCTION: This case report aims to discuss the clinical and radiological outcomes of prolotherapy at a patient whom to total knee prosthesis had been planned but surgery couldn\'t be performed due to co-morbidities.

    CASE PRESENTATION: A 72 year old woman presented with severe pain at her knees for over 5 years. Treatment methods include weight loss, decreasing the weight bearing on the joint, stretching exercises, nonsteroid anti-inflammatory and steroid drugs, and physiotherapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale was applied to measure the osteoarthritis level of the patient: Pain level; 25 points, stiffness level; 10 points, Physical function loss; 80 points, and total WOMAC 115 points. At radiological evaluation, the patient was diagnosed as grade IV osteoarthritis due to significant osteophyte presence and complete joint space narrowing. Six sessions of knee prolotherapy protocol was applied to the patient, one session monthly.

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  • Microperforation prolotherapy: a novel method for successful nonsurgical treatment of atraumatic spontaneous anterior sternoclavicular subluxation, with an illustrative case

    Abstract

    Background

    Surgical repair of an atraumatic spontaneous anterior subluxation of the sternoclavicular joint (herein referred to as the \"SCJ\") is often associated with poor outcome expectations. With traditional treatment, successful conservative therapy usually incorporates major lifestyle alterations. This manuscript discusses a novel approach known as \"microperforation prolotherapy\". To illustrate the technique, the care of a patient who benefitted from this treatment is reviewed.

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  • Complete resolution of avascular necrosis of the human femoral head treated with adipose tissue-derived stem cells and platelet-rich plasma

    Abstract

    We report a case of a 43-year-old man with early stage (stage 1) avascular necrosis (AVN) of the femoral head treated with adipose tissue-derived stem cells (ASCs) and platelet-rich plasma (PRP). ASC-containing stromal vascular fraction was mixed with PRP and hyaluronic acid. This mixture was then injected into the diseased hip under ultrasound guidance. The affected hip was reinjected weekly with additional PRP for 4 weeks. The patient was followed-up with sequential magnetic resonance imaging (MRI) scans at 3, 18, and 21 months after treatment, together with Visual Analogue Scale (VAS) Walking Index, Functional Rating Index, Harris Hip Score, and Range of Motion (ROM) assessments. The patient\'s severe hip pain was considerably improved at 3 months after treatment, with pain scores, ROM and MRI showing near complete resolution of AVN. Pain scores, ROM and MRI at 18 and 21 months after treatment indicated complete resolution of AVN. This case represents the first evidence of complete resolution of early stage AVN of the hip following treatment with ASCs/PRP.

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  • Effect of Autologus Platelet-Rich Plasma on IL-6, MMP-3 and MCP-1 Expression in Synoviocytes from Osteoarthritic Patients Knees

    Abstract

    Nowadays, some studies reported promising results of platelet-rich plasma (PRP) for the treatment of osteoarthritis (OA). However, the effects of PRP on prevention of osteoarthritis in knee joints have been debated. The present study investigated the effects of PRP on osteoarthritisrelated inflammatory cytokines expressed in fibroblast-like synoviocytes (FLS) from osteoarthritic knees. The synovial tissues were harvested from eight osteoarthritic patients who had undertaken total knee arthroplasties (TKAs) and cultured in DMEM containing 10% FBS. Platelet-rich plasma releasate (PRPr) was made by clotting or activation of PRP by citrate. The levels of PDGF-AA and VEGF in PRPr and whole blood were measured with ELISA method. The FLS were isolated and cultured from osteoarthritic knees. The IL-1β stimulated FLS were cultivated with three different conditions (none, 1% and 10% of PRP). To determine the expression of IL-6, MMP-3, and MCP-1, we used reverse transcriptase polymerase chain reaction (RT-PCR). The concentrations of platelet count in PRP were about 7 to 9 times higher than those of whole blood. The levels of PDGF-AA in PRPr were approximately 3 to 4 times higher than those of whole blood. The levels of VEGF in PRPr were also significantly 7 to 18 times higher than those of whole blood. Without induction of the FLS with IL-1β, 1% or 10% PRPr did not reduce expressions of inflammatory proteins (MMP-3, MCP-1), except for IL-6. However, with induction of the FLS with IL-1β, both concentrations (1% and 10%) of PRPr reduced significantly all inflammatory protein expressions (IL-6, MMP-3, MCP-1). PRPr diminished inflammatory IL-1β-mediated effects on human osteoarthritic fibroblast-like synoviocytes. These results suggest that platelet-rich plasma can be a good therapeutic option for the treatment of osteoarthritis.

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  • Pain in Osteoarthritis: Can Prolotherapy Help?

    Osteoarthritis (OA) remains the most common joint disease in the world, and to date, has no cure. Approximately 27 million people in the United States (1) suffer from OA, which is characterized by chronic pain, joint stiffness, structural damage, and bone remodeling and is caused by the pro-gressive loss of cartilage. The prevalence of chronic pain in OA has been estimated to range from 8% to more than 60%, depending on the types of populations studied and the methodologies used (2). Economically, the impact of arthritis on lost productive work time for 2003/2004 was estimated to be $7.1 billion, with 66% of these costs at-tributed to 38% of workers who had pain exacerbations (3). OA-related annual medical costs in 2007 were $6,811 per patient for those newly diagnosed and $6,407 for existing patients. Annual costs of pain-related prescription drugs associated with OA were $965 each for new patients and $1,117 for existing patients (4).

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  • Corticosteroid versus platelet-rich plasma injection in epicondylitis

    Abstract

    Lateral epicondylitis (LE) is often considered an inflammatory disease characterized by tendon microtears that are followed by an incomplete reparative response that leads to chronic pain and decreased function on the upper extremity. A modality that is commonly used for the treatment of LE is the injection of corticosteroids. Evidence supports corticosteroid injections to be an effective short-term intervention that lacks intermediate and long-term relief as well as having negative effects on tenocyte proliferation, which is essential in the tissue healing process. Platelet-rich plasma (PRP) has been shown to be more effective, providing longer positive results with a lower recurrence rate. PRP\'s powerful growth factor stimulates tissue repair and protects tenocytes from the cytotoxic effects caused by corticosteroids. Unfortunately, the efficacy of PRP has been questioned because of past study designs. Nevertheless, recent studies provide practice-changing evidence that supports the use of PRP for the treatment of LE.

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  • Does intra articular platelet rich plasma injection improve function, pain and quality of life in patients with osteoarthritis of the knee? A randomized clinical trial

    Abstract

    We designed a randomized clinical trial with control group, to investigate the effects of platelet rich plasma (PRP) on pain, stiffness, function and quality of life in patients with knee osteoarthritis. Patients were randomly divided in two groups. For both groups of participants, therapeutic exercise was prescribed. In the PRP group, two courses of leukocyte rich PRP (5.6 fold higher platelet concentration) with a 4-week interval was injected. For each participant, Western Ontario and McMaster University\'s Arthritis Index (WOMAC) and the SF-36 questionnaire (Farsi version) were filled at the baseline and 6 months after treatments. Thirty-one patients in the PRP group and 31 patients in the control group were studied. Mean changes of total WOMAC, physical component summery and mental component summery of Short Form-36 in PRP group showed better improvement than control group (P<0.05). This study showed that intra articular PRP knee injection combined with therapeutic exercise can be more effective in pain reduction and improvement of stiffness and quality of life, compared with therapeutic exercise alone.

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  • Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection and dry needling in rotator cuff disease: a randomized controlled trial

    Abstract

    OBJECTIVE: To compare the effects of platelet-rich plasma injection with those of dry needling on shoulder pain and function in patients with rotator cuff disease.

    DESIGN: A single-centre, prospective, randomized, double-blinded, controlled study.

    SETTING: University rehabilitation hospital.

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  • Platelet-Rich Plasma: A Promising Therapy for Recalcitrant Venous Leg Ulcer: A Case Report

    Abstract

    Venous disease is the most common cause of leg ulcers with considerable morbidity and a dramatic negative impact on patient\'s quality of life. Platelet-rich plasma (PRP) is an autologous preparation of platelets in concentrated plasma and contains various growth factors that can modulate healing process. PRP is a simple, safe, affordable procedure for venous ulcer which is therapeutically challenging. Herein, we report a case of recalcitrant non-healing venous leg ulcer treated effectively with PRP therapy and discuss about the promising possibility of autologous PRP as an effective alternative therapeutic modality.

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  • Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial

    Abstract

    PURPOSE: Knee osteoarthritis is a common, debilitating chronic disease. Prolotherapy is an injection therapy for chronic musculoskeletal pain. We conducted a 3-arm, blinded (injector, assessor, injection group participants), randomized controlled trial to assess the efficacy of prolotherapy for knee osteoarthritis.

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  • Microperforation prolotherapy: a novel method for successful nonsurgical treatment of atraumatic spontaneous anterior sternoclavicular subluxation, with an illustrative case

    Abstract

    BACKGROUND: Surgical repair of an atraumatic spontaneous anterior subluxation of the sternoclavicular joint (herein referred to as the \"SCJ\") is often associated with poor outcome expectations. With traditional treatment, successful conservative therapy usually incorporates major lifestyle alterations. This manuscript discusses a novel approach known as \"microperforation prolotherapy\". To illustrate the technique, the care of a patient who benefitted from this treatment is reviewed.

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  • Hyperuricemic PRP in Tendon Cells

    Introduction

    The use of platelet-rich plasma (PRP) to treat tendon pathology has widely expanded in the last five years [1]. PRP is injected within tendons aiming at healing, reducing pain, and improving tendon function [2]. A recent meta-analysis has shown a significant reduction of pain at three years, six years, and one year after PRP treatment in different tendons [3].

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  • Efficacy of Autologous Bone Marrow Concentrate for Knee Osteoarthritis with and without Adipose Graft

    Introduction

    Knee osteoarthritis (OA) is a significant health problem with increasing impact on public health [1]. In 2009 there were approximately 600,000 total knee arthroplasties (TKAs)performed for knee OA, more than double the number performed 10 years earlier [2]. Total or partial joint arthroplasty surgeries are highly invasive procedures, requiringsurgical resection of all or parts of the joint and insertion of a prosthesis [3]. Complications can be significant and include death, pulmonary embolism, stroke, and myocardialinfarction [4-7]. While many patients who undergo TKA experience improved function and decreased symptoms, many others continue to have some degree of ongoing pain. A recent investigation of post-TKA symptoms reported chronic pain in 88% of patients who have had the surgery [8].

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  • Surgery versus Physical Therapy for a Meniscal Tear and Osteoarthritis

    Background

    Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain.

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