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  • Safety and Efficacy of Intra-articular Injection of Platelet-Rich Plasma in Patients With Ankle Osteoarthritis

    Abstract

    Background: An intra-articular injection of platelet-rich plasma (PRP) may be an effective treatment for osteoarthritis (OA). However, its efficacy in ankle OA has not been investigated yet. The purpose of this study was to assess the safety and efficacy of an intra-articular injection of PRP in patients with ankle OA during a 24-week period.

    Methods: Twenty ankles of 20 patients with varus-type ankle OA who received intra-articular injections of PRP were evaluated. PRP was extracted from whole blood by using the double-spin technique. Three injections of 2-mL PRP were administered to the ankle at an interval of 2 weeks under ultrasonographic guidance. Adverse events and efficacy were assessed at 4, 12, and 24 weeks after the last injection. Clinical outcomes were assessed by using the visual analog scale (VAS) for pain, the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q)

    Results: No serious adverse effects were observed during the follow-up period. The VAS and JSSF scale scores significantly decreased from baseline to 4, 12, and 24 weeks after treatment (P < .001). The mean score in the pain-related subscale of the SAFE-Q significantly improved from baseline to 12 weeks after treatment (P = .04). Overall, the amount of pain reduction was maximal at 12 weeks after the last injection, and the effect was reduced at 24 weeks. The patients with late-stage OA had worse scores in all outcomes than those with early-stage OA.

    Conclusion: Intra-articular injections of PRP resulted in no serious adverse effects and significantly reduced pain in the patients with ankle OA. PRP treatment can be safe and effective and may be an option in the treatment of ankle OA.

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  • Platelet rich plasma in treatment of plantar fascitis

    Abstract

    Background: Platelet rich plasma (PRP) has been a breakthrough in the field of medicine especially in the field of orthopaedics for enhancing bone and soft tissue healing. Plantar Fasciitis is a very common problem in the field of orthopaedics and are very difficult to treat and a challenge to orthopaedicians. The aim of our study was to find out the efficacy of autologous PRP in relieving pain in patients with plantar fasciitis.

    Methods: In this study, 25 patients with plantar fasciitis (age above 18 years) were selected. The pain intensity was assessed with visual analogue score initially and during follow up. All subjects were given single autologous intra-lesional PRP injection and the results were assessed using difference in VAS.

    Results: The mean pain score at presentation was 8.08. The mean pain scores at subsequent intervals of 1,2,4,6 months after injection were 4.32, 2.60, 1.88 & 2.00 respectively. (P<0.05 which is statistically significant). The maximum pain relief was seen at 4th month post PRP injection and the pain relief was sustained till the last follow up.

    Conclusions: From our study we have found that Intra-lesional autologous PRP is effective in relieving pain in patients with plantar fasciitis. PRP is biological and can be a safe adjuvant in the treatment of Plantar Fasciitis.

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  • Evaluation of new concept of platelet-rich plasma periarticular injections for pain reduction in patients with temporomandibular joint dysfunctions: a pilot study

    Abstract

    Background: A number of conservative methods are used in the treatment of temporomandibular joint (TMJ) dysfunction pain syndrome. Platelet-rich plasma (PRP) is a natural concentrate of autologous blood growth factor. Periarticular application of PRP and creating of oedema around the TMJ can be very simple approach for treating of TMJ pain instead of intraarticular application.

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  • Leg Symptoms Associated with Sacroiliac Joint Disorder and Related Pain

    Abstract

    Objective: The symptoms of sacroiliac joint (SIJ) disorders are usually detected in the buttock and groin, and occasionally referred to the thigh and leg. However, lumbar disorders also cause symptoms in these same body regions. The presence of a characteristic, symptomatic pattern in the legs would be useful for diagnosing SIJ disorders. This study aimed to identify specific leg symptoms in patients with SIJ pain originating from the posterior sacroiliac ligament and determine the rate of occurrence of these symptoms.

    Patients and Methods: The source population consisted of 365 consecutive patients from February 2005 to December 2007. One hundred patients were diagnosed with SIJ pain by a periarticular SIJ injection (42 males and 58 females, average age 46 years, age range, 18-75 years). A leg symptom map was made by subtracting the symptoms after a periarticular SIJ injection from the initial symptoms, and evaluating the rate of each individual symptom by area.

    Results: Ninety-four patients reported pain at or around the posterior-superior iliac spine (PSIS). Leg symptoms comprised pain and a numbness/tingling sensation; ≥60% of the patients had these symptoms. Pain was mainly detected in the back, buttock, groin, and thigh areas, while numbness/tingling was mainly detected in the lateral to posterior thigh and back of the calf.

    Conclusions: Leg symptoms associated with SIJ pain originating from the posterior sacroiliac ligament include both pain and numbness, which do not usually correspond to the dermatome. These leg symptoms in addition to pain around the PSIS may indicate SIJ disorders.

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  • Role of Ultrasound Guided Platelet-Rich Plasma (PRP) Injection in Treatment of Lateral Epicondylitis

    Abstract

    Background: Lateral epicondylitis is referred to a degenerative disorder that affects the common extensor tendon (CET) where it attaches to the lateral epicondyle of the humerus. Nowadays, one of minimally invasive interventions is platelet-rich plasma (PRP) injection that had been explored in some controlled clinical studies to show its effectiveness in treating lateral epicondylitis through inducing inflammation rather than suppressing it.

    Objectives: The aim of our study was to investigate the effectiveness of ultrasound guided platelet-rich plasma (PRP) injection in treating chronic lateral epicondylitis in addition to identifying the potential sonographic morphological changes in the common extensor tendon (CET) after PRP injection.

    Results: Statistical analysis showed high significant improvement in all ultrasound findings of common extensor tendon (CET) including echotexture, thickness, cross section, partial tear and calcification in majority of patients.

    Conclusion: We concluded that US-guided platelet-rich plasma (PRP) injection for treatment of lateral epicondylitis was a safe, minimally invasive and effective procedure in improving the sonographic and pathological changes of common extensor tendon (CET).

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  • Intratendon Delivery of Leukocyte-Poor Platelet-Rich Plasma Improves Healing Compared With Leukocyte-Rich Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model

    Abstract

    Background: Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo.

    Purpose: This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo.

    Methods: Four weeks after a local injection of collagenase in the Achilles tendon, the following treatments were randomly administered on the lesions: injections of (1) 200 μL of Lp-PRP (n = 8), (2) 200 μL of Lr-PRP (n = 8), or (3) 200 μL of saline (n = 8). Healing outcomes were assessed at 4 weeks after therapy with magnetic resonance imaging (MRI), cytokine quantification, real-time polymerase chain reaction analysis of gene expression, histology, and transmission electron microscopy (TEM).

    Results: MRI revealed that the Lr-PRP and saline groups displayed higher signal intensities compared with the Lp-PRP group with T2 mapping. Histologically, the Lp-PRP group displayed significantly better general scores compared with the Lr-PRP (P = .001) and saline (P < .001) groups. Additionally, TEM showed that the Lp-PRP group had larger collagen fibril diameters than the Lr-PRP group (P < .001). Enzyme-linked immunosorbent assay showed a significantly lower level of catabolic cytokine IL-6 in the Lp-PRP group compared with the Lr-PRP (P = .001) and saline (P = .021) groups. The Lp-PRP group displayed significantly increased expression of collagen I compared with the saline group (P = .004) but not the Lr-PRP group. Both the Lp-PRP and Lr-PRP groups exhibited significantly lower matrix metalloproteinase (MMP)-1 and MMP-3 expression levels compared with the saline group. However, only the Lp-PRP group displayed significantly higher expression of TIMP-1 than the saline group (P = .024).

    Conclusion: Compared with Lr-PRP, Lp-PRP improves tendon healing and is a preferable option for the clinical treatment of tendinopathy.

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  • Platelet Rich Plasma in Osteoarthritis: More than a growth factor therapy

    Abstract

    Osteoarthritis (OA) is the most commonly encountered degenerative joint disorder in clinical medicine and the pain and stiffness caused by osteoarthritis represents a leading cause of physical disability in individuals of retirement age. Treatment options for OA patients are limited and largely targeted to pain management. Such is the mechanism behind the most commonly prescribed OA therapies including acetaminophen, NSAIDs, opioids, and steroids. However, these palliative pain management tools do not address the underlying pathophysiology of OA disease. This leaves a significant clinical unmet need for disease modifying OA therapies. Growth factor therapies and regenerative medicine strategies are emerging as promising alternatives to palliative care because these treatments bring significant potential to control chronic inflammation, enhance cartilage repair, and restore other joint tissues to a healthy state. Interestingly, a Clinicaltrials.gov search using the terms "osteoarthritis" and "growth factor" identified 43 relevant studies. Of these, only 26% used growth factor therapies directly, including FGF-18, BMP-2, and transgenic human chondrocytes producing TGF-b1. 23% of the studies were dedicated to inhibitors of NGF. The overwhelming majority of studies (47%) used autologous blood products, especially platelet rich plasma (PRP), which constituted 33% of the total studies. This was interesting because although platelets in PRP do indeed harbor large quantities of different growth factors that can affect the status of the treated tissue, growth factors represent only a single aspect of the bioactivity of platelets. Furthermore, platelets represent only one aspect of the potential bioactivity of PRP. Depending upon the methods used for PRP generation, it may also contain other physiologically important components of the whole blood from which it is derived. Recent studies indicate non-platelet components of whole blood such as red blood cells and leukocytes are essential for normal platelet function, including growth factor release. Therefore, this narrative review discusses PRP from a physiological context that explores beyond platelet growth factors to encompass and illuminate roles of non-platelet cells in the bioactivity of PRP, and how these additional mechanisms lead to the conclusion that PRP can be much more than a growth factor therapy.

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  • Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials

    Abstract

    Purpose: To use meta-analysis techniques to evaluate the efficacy and safety of platelet-rich plasma (PRP) injections for the treatment knee of osteoarthritis (OA).

    Methods: We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane database through April 2016 to identify Level I randomized controlled trials that evaluated the clinical efficacy of PRP versus control treatments for knee OA. The primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores. The primary outcomes were compared with their minimum clinically important differences (MCID)ddefined as the smallest difference perceived as important by the average patient.

    Results: We included 10 randomized controlled trials with a total of 1069 patients. Our analysis showed that at 6 months postinjection, PRP and hyaluronic acid (HA) had similar effects with respect to pain relief (WOMAC pain score) and functional improvement (WOMAC function score, WOMAC total score, International Knee Documentation Committee score, Lequesne score). At 12 months postinjection, however, PRP was associated with significantly better pain relief (WOMAC pain score, mean difference - 2.83, 95% confidence interval [CI] - 4.26 to - 1.39,P

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  • Platelet-Rich Plasma in Regenerative Medicine

    Abstract

    The clinical application of platelet-rich plasma (PRP) has been increasing sharply in the last two decades. Its role as a potential regenerative agent and ease of application have allowed it to take huge share in the fast-evolving biological therapy field. The reported effect of PRP on a range of tissue types including bone, cartilage, tendon and muscle has attracted clinical interest in fields such as trauma, orthopaedic, maxillofacial and plastic surgery where effective healing of tissues is critical for successful outcome. The results of in vitro and animal studies that largely report positive effects of PRP on cellular and matrix regeneration have been the main drive for its translation to clinical settings. Despite the lack of appropriately powered trials, PRP administration remains an attractive strategy given its cost-effective, minimally invasive nature and the autologous nature of PRP. In this chapter, the current literature on the use of PRP in regenerative medicine is reviewed highlighting both some of the controversy surrounding this approach and some emerging clinical applications. A new PRP classification system is presented to allow better description of the variable clinical PRP products and their correlated outcome.

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  • Six-month efficacy of platelet-rich plasma for carpal tunnel syndrome: A prospective randomized, single-blind controlled trial

    Abstract

    Recently, a few small reports with short follow-up period have shown clinical benefits of platelet-rich plasma (PRP) for peripheral neuropathy including one pilot study and one small, non-randomized trial in patients with carpal tunnel syndrome (CTS). Therefore, we conducted a randomized, single-blind, controlled trial to assess the 6-month effect of PRP in patients with CTS. Sixty patients with unilateral mild-to-moderate CTS were randomized into two groups of 30, namely the PRP and control groups. In the PRP group, patients were injected with one dose of 3 mL of PRP using ultrasound guidance and the control group received a night splint through the study period. The primary outcome measure was the visual analog scale (VAS) and secondary outcome measures included the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score, the cross-sectional area (CSA) of the median nerve (MN), electrophysiological findings of the MN, and finger pinch strength. The evaluation was performed before treatment and at 1, 3, and 6 months post-injection. The PRP group exhibited a significant reduction in the VAS score, BCTQ score, and CSA of MN compared to the those of control group 6 months post-treatment (p < 0.05). Our study demonstrates that PRP is a safe modality that effectively relieves pain and improves disability in the patients with CTS.

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  • Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain

    Abstract

    Background: The use of NSAID medications is a well-established effective therapy for both acute and chronic nonspecific neck and back pain. Extreme complications, including gastric ulcers, bleeding, myocardial infarction, and even deaths, are associated with their use. An alternative treatment with fewer side effects that also reduces the inflammatory response and thereby reduces pain is believed to be omega-3 EFAs found in fish oil. We report our experience in a neurosurgical practice using fish oil supplements for pain relief.

    Methods: From March to June 2004, 250 patients who had been seen by a neurosurgeon and were found to have nonsurgical neck or back pain were asked to take a total of 1200 mg per day of omega-3 EFAs (eicosapentaenoic acid and decosahexaenoic acid) found in fish oil supplements. A questionnaire was sent approximately 1 month after starting the supplement.

    Results: Of the 250 patients, 125 returned the questionnaire at an average of 75 days on fish oil. Seventy-eight percent were taking 1200 mg and 22% were taking 2400 mg of EFAs. Fifty-nine percent discontinued to take their prescription NSAID medications for pain. Sixty percent stated that their overall pain was improved, and 60% stated that their joint pain had improved. Eighty percent stated they were satisfied with their improvement, and 88% stated they would continue to take the fish oil. There were no significant side effects reported.

    Conclusion: Our results mirror other controlled studies that compared ibuprofen and omega-3 EFAs demonstrating equivalent effect in reducing arthritic pain. omega-3 EFA fish oil supplements appear to be a safer alternative to NSAIDs for treatment of nonsurgical neck or back pain in this selective group.

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  • The Time Has Come to Try Intra-articular Platelet-Rich Plasma Injections for Your Patients With Symptomatic Knee Osteoarthritis

    Abstract

    Platelet-rich plasma injections, in a systematic review and meta-analysis of 10 Level I randomized control trials, were found to provide more pain relief and better functional outcomes than hyaluronic acid in patients with knee osteoarthritis at 12 months after injection. The time has come for those of us who have not yet tried platelet-rich plasma injections in our patients with symptomatic knee osteoarthritis to do so.

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  • Conservative Treatment of Ankle Osteoarthritis: Can Platelet-Rich Plasma Effectively Postpone Surgery?

    Abstract

    Osteoarthritis is the most common and disabling of the orthopedic diseases. Currently, the conservative treatment of osteoarthritis is limited to symptomatic treatment, whose goal is to improve function and pain control. Ankle osteoarthritis is relatively uncommon, in contrast to osteoarthritis of the hip and knee, and the therapeutic options (both pharmacologic and surgical) are limited, with surgery providing poorer and less predictable results. The effectiveness of platelet-rich plasma injections for osteoarthritis is still controversial, especially so for ankle arthritis, owing to the lack of evidence in the present data. We retrospectively evaluated the mid- to long-term clinical results (mean follow-up of 17.7 months) for platelet-rich plasma injections in 20 patients (20 ankles) with ankle osteoarthritis. We evaluated the presence of pain using the visual analog scale, function using the Foot and Ankle Disability Index, and subjective satisfaction. The pre- and post-treatment scores, obtained from the clinical records and from telephone interviews during the follow-up period, were compared using the Student t test. We found a strong positive effect for 4 platelet-rich plasma injections (injected once a week) on pain (p = .0001) and function (p = .001), with 80% of patients very satisfied and satisfied, and only 2 patients (10%) required surgery because of early treatment failure. These results suggest that the use of platelet-rich plasma injection is a valid and safe alternative to postpone the need for surgery.

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  • Glucose Adsorption to Chitosan Membranes Increases Proliferation of Human Chondrocyte via Mammalian Target of Rapamycin Complex 1 and Sterol Regulatory Element-binding Protein-1 Signaling

    Abstract

    Background: Osteoarthritis (OA) is currently still an irreversible degenerative disease of the articular cartilage. Recent, dextrose (D-glucose) intraarticular injection prolotherapy for OA patients has been reported to benefit the chondrogenic stimulation of damaged cartilage. However, the detailed mechanism of glucose's effect on cartilage repair remains unclear. Chitosan, a naturally derived polysaccharide, has recently been investigated as a surgical or dental dressing to control breeding. Therefore, in this study, glucose was adsorbed to chitosan membranes (CTS-Glc), and the study aimed to investigate whether CTS-Glc complex membranes could regulate the proliferation of human OA chondrocytes and to explore the underlying mechanism.

    Methods: Human OA and SW1353 chondrocytes were used in this study. The experiments involving the transfection of cells used SW1353 chondrocytes. A specific inhibitor and siRNAs were used to investigate the mechanism underlying the CTS-Glc-regulated proliferation of human chondrocytes.

    Results: We found that CTS-Glc significantly increased the proliferation of both human OA and SW1353 chondrocytes comparable to glucose- or chitosan-only stimulation. The role of mammalian target of rapamycin complex 1 (mTORC1) signaling, including mTOR, raptor, and S6k proteins, has been demonstrated in the regulation of CTS-Glc-increased human chondrocyte proliferation. mTORC1 signaling increased the expression levels of maturated SREBP-1 and FASN and then induced the expressions of cell cycle regulators, i.e., cyclin D, cyclin-dependent kinase-4 and -6 in human chondrocytes.

    Conclusion: This study elucidates the detailed mechanism behind the effect of CTS-Glc complex membranes in promoting chondrocyte proliferation and proposes a possible clinical application of the CTS-Glc complex in the dextrose intraarticular injection of OA prolotherapy in the future to attenuate the pain and discomfort of OA patients.

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  • Study comparing the efficacy of platelet rich plasma versus steroid versus placebo in lateral epicondylitis

    Abstract

    Background: Lateral epicondylitis is seen more commonly in non-athletes than athletes. Non-operative methods are the mainstay of treatment being effective in more than 95% of cases. Platelet rich plasma (PRP) has shown promising results in many studies as compared to steroid injection & other modes of conservative management. Hence, this study was done to evaluate PRP efficacy in our clinical setup and in the people of age group most commonly being affected.

    Methods: This randomized study was conducted at Narayana Medical College Hospital, Nellore, for a period of two years from December 2014 to June 2016 on 150 consenting patients diagnosed as suffering from lateral epicondylitis. Using lottery method for randomization the patients were divided into three groups, based on which the treatment was received. Group –N with 50 patients received 3 ml of normal saline as placebo. Group – with 50 patients received 3 ml of extracted PRP injection. Group –S with 50 patients received depot preparation of 40 mg of methyl prednisiolone injected into the affected area. The data collected and recorded in the appropriate proforma. Post therapy assessment was done using with Oxford elbow score.

    Results: The overall mean ages of the patients in the three groups (Group P, Group S and Group N) are 38.62 ±7.53, 37.82 ±7.79 and 36.3 ±6.93 respectively. Female preponderance was observed in all the groups. Most common presenting complaint was elbow pain seen in 100% of cases. Most common side involved was the dominant side, right side involvement was seen in 136 cases and left side in 14 cases. The Oxford elbow score pre-treatment in all the groups was not statistically significant and the Oxford elbow score at the end of 12 weeks and 24 weeks treatment showed that PRP and steroid was better than normal saline in control of pain.

    Conclusion: Lateral epicondylitis or tennis elbow is a painful debilitating condition of elbow, which creates disturbance in functional activities. A single injection of PRP at the site of the elbow pain resulted in relief of pain in patients with longer duration as compared to local steroids to other conservative treatments.

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  • Effectiveness of Prolotherapy in The Treatment of Chronic Rotator Cuff Lesions

    Abstract

    Background: Rotator cuff lesions are one of the major causes of shoulder pain and dysfunction. Numerous non-surgical treatment modalities have been described for chronic rotator cuff lesions, but the debate continues over the optimal procedure. The aim of this report is to present the results of prolotherapy in the treatment of chronic refractory rotator cuff lesions.

    Hypothesis: Dextrose prolotherapy will reduce pain and improve shoulder function and patient satisfaction.

    Material and Methods: We recruited 120 patients with chronic rotator cuff lesions and symptoms that persisted for longer than 6 months. Patients were divided into two groups: one treated with exercise (control group; n = 60) and the other treated with prolotherapy injection (prolotherapy group; n = 60). In the latter, ultrasound-guided prolotherapy injections were applied under aseptic conditions. In the former, patients received a physiotherapy protocol three sessions weekly for 12 weeks. Both groups were instructed to carry out a home exercise program. Clinical assessment of shoulder function was performed using a visual analog scale (VAS) for pain, Shoulder Pain and Disability Index (SPADI), Western Ontario Rotatory Cuff (WORC) Index, patient satisfaction, and shoulder range of motion. Patients were examined at baseline, weeks 3, 6, and 12, and last follow-up (minimum of one year).

    Results: A total of 101 patients (44 controls and 57 in the prolotherapy group) completed all study protocols and were included in the study. Using a within-group comparison, both groups achieved significant improvements over baseline, as measured by the VAS, SPADI, WORC index, and shoulder range of motion (p < 0.001). Using a between-group comparison, a significant difference was found in the VAS scores at baseline, weeks 3, 6, and 12, and last follow-up. In addition, significant differences were found in the SPADIs and WORC indices at weeks 6 and 12 and the last follow-up. Significant differences were found in shoulder abduction and flexion at week 12 and last follow-up, and in internal rotation at last follow up. However, no significant was found in external rotation at any follow-up period. In the prolotherapy group, 53 patients (92.9%) reported excellent or good outcomes; in the control group, 25 patients (56.8%) reported excellent or good outcomes.

    Conclusion: Prolotherapy is an easily applicable and satisfying auxiliary method in the treatment of chronic rotatory cuff lesions.

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  • Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

    Abstract

    Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration.

    Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1-2-3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media.

    Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13.

    Conclusion:These results suggest that PRP could be a potential therapeutic tool for the treatment of OA.

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  • The Use of Platelet-Rich and Platelet-Poor Plasma to Enhance Differentiation of Skeletal Myoblasts

    Abstract

    Objectives: Platelet-rich plasma (PRP) has been has been used to augment tissue repair and regeneration after musculoskeletal injury. However, there is increasing clinical evidence that PRP, and related blood products, do not show a consistent clinical effect. The purpose of this study is to compare the effects of non-neutrophil containing PRP (LP-PRP), modified LP-PRP (Mod LP-PRP) where TGF-β1 and myostatin (MSTN) were depleted, and platelet poor plasma (PPP) on human skeletal muscle myoblast (HSMM) differentiation. Our hypothesis was that LP-PRP would lead to myoblast proliferation, not differentiation, while modifications of PRP preparations will increase myoblast differentiation, which is necessary for skeletal muscle regeneration.

    Methods: Blood was simultaneously processed from eight healthy human donors to create LP-PRP, Mod-LP-PRP, PPP and second spin (ss) PRP and Mod-PRP groups. Mod-PRP was created using antibodies attached to sterile beads to remove TGF- β1 and MSTN. The biologics were then individually added to human skeletal muscle myoblasts (HSMM) and were analyzed over four days. Analysis for induction into myoblast proliferation and differentiation pathways included Western blot and RT-PCR, as well as confocal microscopy to assess for polynucleated myotubule formation.

    Results:LP-PRP treatment lead to increased myoblast proliferation compared to PPP (1.01 x 106 vs 5.1 x 105 cells), but showed no evidence differentiation into muscle cells either by myotubule formation or via inducing myosin heavy chain (MHC) RNA compared to negative controls (0.1x fold change; p>0.05). TGF- β1 and MSTN were successfully depleted in Mod-PRP, but this modification did little to improve myoblast differentiation (0.2x fold change MHC RNA vs control; p>0.05). Application of PPP to cultures induced myoblast differentiation that included visible multinucleated myotubule formation and MHC induction compared to negative controls (9.8x fold change; p<0.05). A second centrifugal spin (removes platelets) lead to a significant increase in myoblast differentiation in PRP and Mod-PRP preparations, similar to the level of PPP and the 2% horse serum positive control (8.0x vs 6.7x vs 9.8x vs 6.0x fold increase in MHC RNA, respectively; all p<0.05 compared to LP-PRP, Mod-LP-PRP and negative controls). Western blot and RT-PCR analyses confirmed that MSTN and TGF-β1 were further depleted in all groups, including Mod-LP-PRP, that were subjected to a second spin.

    Conclusion: PPP, and PRP preparations subjected to a second spin to remove platelets, lead to induction of myoblast cells into the muscle differentiation pathway, while unmodified PRP lead to induction into the proliferation pathway. These results indicate that traditionally formulated PRP should not be used to induce muscle regeneration. Laboratory evidence suggests that platelet poor plasma (PPP) or LP-PRP subjected to a second spin to remove platelets should be used to stimulate myoblast differentiation, which is necessary for skeletal muscle regeneration. Clinical studies will be required to confirm the effect of these biologics on muscle regeneration.

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  • Proliferative injection therapy for osteoarthritis: a systematic review

    Abstract

    Purpose: To systematically analyse randomised controlled trials (RCTs) about efficacy and safety of proliferative injection therapy (prolotherapy) for treatment of osteoarthritis (OA).

    Methods: CENTRAL, Embase and MEDLINE were searched. Two reviewers independently conducted screening and data extraction. RCTs were assessed with the Cochrane risk of bias tool. Type of treatment, study design, dosing, efficacy outcomes and safety outcomes were analysed. The protocol was registered in PROSPERO (CRD42016035258).

    Results: Seven RCTs were included, with 393 participants aged 40-75 years and mean OA pain duration from three months to eight years. Follow-up was 12 weeks to 12 months. Studies analysed OA of the knee joint (n = 5), first carpometacarpal joint (n = 1) and finger joints (n = 1). Various types of prolotherapy were used; dextrose was the most commonly used irritant agent. All studies concluded that prolotherapy was effective treatment for OA. No serious adverse events were reported. The studies had considerable methodological limitations.

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  • Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

    Abstract

    Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.

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