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Objectives: This study aims to compare the effectiveness of single, double, and triple doses of intra-articular (IA) platelet rich plasma (PRP) in early stages of osteoarthritis (OA) of the knee. Patients and methods: This single-blind, randomized, superiority trial included a total of 180 knees of 90 patients (22 males, 68 females; mean age: 47.9 years; range, 36 to 60 years) with bilateral OA knee of Kellgren-Lawrence Grade 1-2 between May 2017 and December 2018. The patients were randomized (30 in each group) to receive single, double, or triple doses of IA PRP (two weeks apart in repeat injections). The outcome measures were Visual Analog Scale, International Knee Documentation Committee Score, Knee Injury and Osteoarthritis Outcome Score, and Tegner Lysholm Knee Score. The assessor of outcome was blinded. The scores were collected before intervention and at six weeks, three months, six months, and one year after the intervention. Results: All patients completed the study. All three groups were comparable with respect to demographic and disease characteristics. All four scores were comparable among the three groups before intervention and at six weeks, three months, and six months. However, at one-year follow-up, the three-dose group showed superiority to others in terms of all four scores. All three groups showed improvement until six months and deterioration thereafter, which was only marginal in the three-dose group. All groups showed a statistically significant improvement of scores compared to baseline scores at one year. There were no major complications. Conclusion: The IA administration of three doses of PRP yields superior outcome to single and double doses at the end of one year. Repeat doses are probably needed to sustain the benefit achieved at one year.

Context: Internal derangements of temporomandibular joint (TMJ) with associated symptoms which do not respond to conservative therapies are refractory cases of temporomandibular joint dysfunction syndrome (TMD). Minimally invasive techniques like arthrocentesis and platelet rich plasma (PRP) injections are usually employed to improve TMJ symptoms and function in these cases. Aims: To compare PRP with arthrocentesis for evaluating the effectiveness of PRP in relieving symptoms of refractory TMJ pain dysfunction syndrome. Setting and Design: A clinical study was carried out on 52 patients of refractory Temporomandibular joint dysfunction syndrome. The patients were divided in two groups that is Group A - test group and Group B -control Group. Methods and Material: Group A consisted of 26 patients who underwent intraarticular PRP injection in TMJ and Arthrocentesis of TMJ was done in 26 patients of Group B. TMJ pain, Maximium Interincisal opening and TMJ clicking were assessed among the group as well as between the groups over a period of 6 months. Statistical Analysis Used: Repeated Measure ANOVA was used to compare the parameters within the groups and T test was used for group comparison at 0.05 level of significance. Result: There was statistically significant difference in pain intensity improvement 1 ± 0.75 versus 3.17 ± 2.13, maximum interincisal opening 39.86 ± 2.86 versus 37.59 ± 4.03 and clicking 6 versus 16 between the PRP group and arthrocentesis group at P < 0.05. Conclusions: Intraarticular PRP injection for the management of refractory TMD is more effective than arthrocentesis in reducing symptoms and functional improvement.

This prospective study was conducted for the clinical evaluation of pain severity and knee functionality following PRP injections with different leukocyte (WBC) concentrations applied to cases diagnosed with knee osteoarthritis. A total of 109 patients were included in the study. According to the leukocyte content the PRP injections were prepared as low-leukocyte content PRP (P-PRP) and high concentration leukocyte content PRP (L-PRP). Patients were divided into 2 groups. Group 1 (n=44) received low-leukocyte content PRP and Group II (n = 65) received high-leukocyte content PRP. The patients were evaluated clinically with Visual Analog Scale (VAS) and Knee Society Score (KSS). The changes in the PLT levels of the L-PRP group after the procedure compared to the levels prior to the procedure were found to be statistically significantly greater than the changes in the PPRP group. The mean VAS score of all the cases before treatment was 9.05±0.91 and this score decreased to 3.71±1.46 within 12 months. The increases in the mean Knee Society Score (KSS) values were determined as 16.92±1.97 within 6 months and 16.89±2.97 within 12 months in the P-PRP group and 19.71±1.24 within 6 months and 19.86±0.42 within 12 months in the L-PRP group. The most important aspect of this study is that, in contrast to many other studies, the results continued after the 6th month and were reported to be good in the 12th month. It was also recorded that L-PRP was clinically superior to P-PRP in the treatment of early stage knee osteoarthritis.

Made available in DSpace on 2021-06-25T12:26:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The aim of this study was to evaluate the in vivo repair using an experimental model of osteoarthritis of the temporomandibular joint in rabbits, treated with hyaluronic acid (HA), isolated or combined with platelet rich plasma (PRP). Forty New Zealand rabbits were divided into 4 groups: G1 - normal TMJ, G2 - lesion / untreated, G3 - lesion / HA, and G4 - lesion / PRP + HA. The disc and the condyle were evaluated using radiographies, macro and microscopic analysis through routine histotechnique, Picrosirius red staining and immunohistochemistry. The results were evaluated by descriptive and inferential statistics. Macroscopically, the disc in the treated groups presented, in most of the specimens, partial or total filling of the defect. Histological analysis confirmed the presence of mineralized material, near and distant perforation, as well as decreased cellularity and fibrosis. The collagen I was demonstrated in higher amounts when compared to type III collagen, independently of the group and period evaluated; in the condyle, G3 and G4 presented significant higher percentage of type I collagen, than G2. In conclusion, the groups that were treated with HA and PRP combined with HA presented no significant differences in microscopic pattern. The macroscopic finding that in some samples in HA treated group and one sample in PRP + HA group presented complete filling of the perforation let us to conclude that new experiments adding more sensitive methods may clear the influence of these treatments in reduce the damage in the osteochondral surface related the lesioned disc. Sao Paulo State Univ, UNESP, Inst Sci & Technol, Dept Biosci & Oral Diag, Ave Eng Francisco Jose Longo 777, BR-12245000 Sao Jose Dos Campos, SP, Brazil Sao Paulo State Univ, UNESP, Inst Sci & Technol, Dept Dent Mat & Prosthesis, Ave Eng Francisco Jose Longo 777, BR-12245000 Sao Jose Dos Campos, SP, Brazil Sao Paulo State Univ, UNESP, Inst Sci & Technol, Dept Biosci & Oral Diag, Ave Eng Francisco Jose Longo 777, BR-12245000 Sao Jose Dos Campos, SP, Brazil Sao Paulo State Univ, UNESP, Inst Sci & Technol, Dept Dent Mat & Prosthesis, Ave Eng Francisco Jose Longo 777, BR-12245000 Sao Jose Dos Campos, SP, Brazil FAPESP: 16/23446-2 FAPESP: 18/13473-8

Background: Delayed healing of diabetic wounds has been well-documented. Currently, the use of platelet-rich plasma (PRP) has attracted great attention in many medical fields including wound healing. Aim: Histological, immunohistochemical and ultrastructural evaluation of the effect of PRP on wound healing in the tongue of normal and Streptozotocin-induced diabetic albino rats. Methodology: A total number of 108 adult male albino rats with average weight 200gm, were used in the study. The animals were classified into two main groups: non-diabetic and diabetic groups. Each group was further divided into three subgroups: non- treated wound, PRP-treatment before wound, and PRP-treatment after wound. Tongue specimens were dissected on postoperative days 1, 3, and 7. The specimens were examined histologically by H&E, immunohistochemically by p63 and vimentin, and ultra-structurally by TEM. Results: The most accelerated wound healing was revealed in the subgroups treated with PRP before the wound, whether non-diabetic or diabetic, which occurred very early at the 3rd day postoperative in both cases. While complete wound healing was revealed at the 7th day postoperative in both the non-diabetic and diabetic subgroups treated with PRP after the wound, which was like the non-diabetic control subgroup. Whilst, the diabetic non-treated subgroup only showed partial wound healing at the 7th day postoperative. Conclusion: A single injection of PRP could be used as a prophylactic to prevent expected impaired wound healing in diabetic oral mucosal wounds and to enhance wound healing in non-diabetic wounds. PRP could be used as a therapeutic to enhance wound healing in diabetic and non-diabetic oral mucosal wounds. Key Words: platelet rich plasma, wound healing, diabetes, rat, tongue, p63, vimentin, TEM BACKGROUND: Delayed healing of diabetic wounds has been well-documented. At present, the use of platelet-rich plasma (PRP) has attracted great attention in many medical fields including wound healing. AIM: Histological, immunohistochemical, and ultrastructural evaluation of the effect of PRP on wound healing in the tongue of normal and streptozotocin-induced diabetic albino rats. METHODOLOGY: A total number of 108 adult male albino rats with average weight 200 g were used in the study. The animals were classified into two main groups: Non-diabetic and diabetic groups. Each group was further divided into three subgroups: Non-treated wound, PRP-treatment before wound, and PRP-treatment after wound. Tongue specimens were dissected on post-operative days 1, 3, and 7. The specimens were examined histologically by H&E, immunohistochemically by p63 and vimentin, and ultrastructurally by TEM. RESULTS: The most accelerated wound healing was revealed in the subgroups treated with PRP before the wound, whether non-diabetic or diabetic, which occurred very early at the 3rd day post-operative in both cases. While complete wound healing was revealed at the 7th day post-operative in both the non-diabetic and diabetic subgroups treated with PRP after the wound, which was like the non-diabetic control subgroup. While, the diabetic non-treated subgroup only showed partial wound healing at the 7th day post-operative. CONCLUSION: A single injection of PRP could be used as a prophylactic to prevent expected impaired wound healing in diabetic oral mucosal wounds and to enhance wound healing in non-diabetic wounds. PRP could be used as a therapeutic to enhance wound healing in diabetic and non-diabetic oral mucosal wounds.

Background To compare the clinical efficacy of platelet rich plasma (PRP) subacromial injection and extracorporeal shock wave therapy (ESWT) on refractory non-calcific partial thickness supraspinatous tendon tear. Results Significant improvement in all outcome measures achieved in both groups at 4 weeks follow-up period (the end of treatment course) (P< 0.05). At 12 weeks follow-up period, group I, showed significant improvement in all outcome measures compared to baseline and group II; however, in group II, there was no significant difference compared to baseline; moreover, deterioration in the previous improvement was noticed. Conclusion Both PRP (group I) and ESWT (group II) are effective therapeutic methods in the management of refractory non-calcific partial thickness supraspinatous tendon tear; however, PRP (group I) has better long-term effects on both pain and function.

Background Carpal tunnel syndrome (CTS) is the most common peripheral entrapment neuropathy. Typical symptoms and signs include numbness, tingling, pain, or burning sensation in the digits supplied by the median nerve and/or nocturnal paresthesia. Treatments of CTS range from conservative measures to surgical decompression of the median nerve. Results The PRP group showed a statistically significant reduction in the visual analog scale, Boston Carpal Tunnel Syndrome Questionnaire, for the severity and the functional capacity scores, and cross-sectional area of the median nerve compared to those of control group 3 months post-treatment (p < 0.05). Conclusions Platelet-rich plasma injection in CTS relieves pain and symptom severity and improves functional status but not significantly improve the electrophysiological parameters.

Purpose: Faecal incontinence (FI) is a frequent condition that can occur due to different causes; with negative impact on self-esteem and quality of life, secondary morbidity, disability and significant costs. For its treatment there is a wide range of options, being medical treatment, hygienic dietary modifications and biofeedback, the first line of treatment; reserving surgery for patients who do not respond or with severe FI; this with variable success rates and high cost. This study has the primary aim to assess the efficacy and describe the Technique of Application of Autologous Fat with Platelet Rich Plasma (AFPRiP) in patients with faecal incontinence as well as secondary endpoints of quality of life, manometric and ultrasound evaluation, safety of implantation, and complications. Methods: A single-centre prospective, experimental study, was conducted from January 2017 to February 2018 in Domingo Luciani Hospital. Wexner and FIQL scores were filled preoperative and compared at follow-up at 3, 6 and 12 months as well as anorectal manometry and endoanal ultrasound were performed before and 6 months after surgery. Results: Twelve patients were operated, mean time 43 min, no major complications. Wexner finding continence improvement from 10.4 pre to 4 in the 3rd month (p = 0.066) 4.74 at the 6th month (p = 0.001) and 5 at one year (p = 0.001); that is, improvement of >50% in 83.4%. FIQL 50.9 prior to 98.6 at 3rd month (p = 0.001) 95.5 to 6th month (p = 0.001) and 91.3 a year (p = 0.066). Conclusions: We conclude that AFPRiP is innovative, safe and with adequate results. Resumo Objetivo: A incontinência fecal é uma condição frequente que pode ocorrer devido a diferentes causas, com impacto negativo na autoestima e qualidade de vida, morbidade secundária, incapacidade e custos significativos. Existem várias opções para o manejo da incontinência fecal; o tratamento médico, as modificações higiênicas da dieta e o biofeedback, são os de primeira linha. A cirurgia é recomendada apenas para pacientes que não respondem ao tratamento de primeira linha ou aqueles com incontinência fecal grave; as taxas de sucesso são variáveis e o custo do tratamento cirúrgico é elevado. Este estudo teve como objetivo principal avaliar a eficácia e descrever a técnica de aplicação de gordura autóloga com plasma rico em plaquetas (AFPRiP) em pacientes com incontinência fecal; o estudo também avaliou parâmetros secundários de qualidade de vida, manométricos e ultrassonográficos, bem como a segurança da implantação e suas complicações. Métodos: Um estudo experimental prospectivo, de centro único, foi realizado de janeiro de 2017 a fevereiro de 2018 no Hospital Domingo Luciani. A escala de Wexner e o FIQL foram preenchidos no pré-operatório e comparados no seguimento de três, seis e 12 meses; manometria anorretal e ultrassonografia endoanal foram realizadas antes e seis meses após a cirurgia. Resultados: Doze pacientes foram operados; o tempo médio da cirurgia foi de 43 minutos, sem maiores complicações. Na escala de Wexner, observou-se melhora na continência: de 10,4 pré-operatório a 4 no terceiro mês (p = 0,066), 4,74 no sexto mês (p = 0,001) e 5 em um ano (p = 0,001), uma melhoria de 83,4%. Já o FIQL evoluiu de 50,9 no período pré-operatório para 98,6 no terceiro mês (p = 0,001), 95,5 no sexto mês (p = 0,001) e 91,3 em um ano (p = 0,066). Conclusões: A AFPRiP é uma técnica inovadora, segura e que apresenta resultados adequados.

Objectives The research aims to assess the regenerative potential of Platelet Rich Plasma (PRP) versus Platelet Rich Fibrin (PRF) scaffolds in immature permanent maxillary central incisors with necrotic pulps, clinically and radiographically. Trial design Double blinded parallel randomized controlled trial was implemented to identify the results. Subject & methods The proposed study was conducted among 30 patients with maxillary necrotic permanent immature central incisors but only 26 patients fulfilled the study requirements. Group I was treated with PRP and Group II with PRF scaffolds. Follow up has been done every 3 months for one year. Primary outcomes were measured clinically: Pain, Mobility, Swelling, and Sinus/fistula. Radiographically: increase root length and width. Secondary outcomes were clinically: Discoloration and Sensibility test. Radiographically: increase in bone density measurements and decrease in apical diameter. Standardized radiographs were collected during the follow up period, and radiographic changes were measured by using Image J software. Statistical analysis was performed on 25 patients who had completed the study. Results All 25 patients' teeth were survived during the 12-month follow-up period. PRP showed marginal increase in radiographic root length and width, periapical bone density and a decrease in apical diameter. No statistical significant differences were observed when it was compared with PRF. The teeth which were treated did not respond to sensibility test at the end of the study. PRF displayed statistical significant higher amount of crown discoloration when compared to PRP group. Conclusions For necrotic immature teeth, revascularization using PRP is an appropriate alternative to PRF and showed excellent 12-months prognosis.

Thrombin generation (TG) is a better determinant of the overall function of the hemostatic system than routinely used clotting time-based assays and can be studied more in detail by thrombin dynamics analysis. Platelet poor plasma is often used to measure TG, however, measuring the contribution of the platelets is also important as patients with a low platelet count or with dysfunctional platelets have an increased risk of developing bleeding. In this study, platelet rich plasma (PRP) was collected from 117 healthy individuals. PRP was measured undiluted and diluted to a varying platelet concentration of 10*109/L to 400*109/L. Prothrombin conversion and thrombin inactivation were calculated from the data obtained by the TG parameters and coagulation factor levels (antithrombin, α2Macroglobulin (α2M) and fibrinogen). Reference ranges of TG and thrombin dynamics in PRP of 117 healthy individuals were established. Peak, velocity index and the maximum rate of prothrombin conversion increased linearly with platelet count, but endogenous thrombin potential reached a maximum at 150*109/L as seen in a subset population (n = 20). More extensive analysis revealed that a platelet count below 50*109/L did not affect TG parameters (except for the ETP). Correlation analysis indicated that the platelet count mainly affected the rate of prothrombin conversion. Inhibition of thrombin by antithrombin and α2M increased with increasing TG, but the ratio of inhibition by antithrombin or α2M remained the same independently of the total thrombin formed. In conclusion, TG and thrombin dynamics were assessed in PRP of healthy donors to provide reference values for future TG studies in PRP. Increasing the platelet count mainly affected the rate of prothrombin conversion and TG, rather than the total amount of thrombin formed.

Objectives: A retrospective case-series study comparing autologous activated platelet-rich plasma (AA-PRP) versus autologous non-activated platelet-rich plasma (A-PRP) in hair re-growth was reporte...

Current surgical reconstruction for soft tissue replacement involves lipotransfer to restore soft tissue replacements but is limited by survival and longevity of the fat tissue. Alternative approaches to overcome these limitations include using biodegradable scaffolds with stem cells with growth factors to generate soft tissue. Adipose derived stem cells (ADSCs) offer great potential to differentiate into adipose, and can be delivered using biodegradable scaffolds. However, the optimal scaffold to maximise this approach is unknown. This study investigates the biocompatibility of nanocomposite scaffolds (POSS-PCL) to deliver ADSCs with and without the addition of growth factors using platelet rich plasma (PRP) in vivo. Rat ADSCs were isolated and then seeded on biodegradable scaffolds (POSS-PCL). In addition, donor rats were used to isolate PRP to modify the scaffolds. The implants were then subcutaneously implanted for 3-months to assess the effect of PRP and ADSC on POSS-PCL scaffolds biocompatibility. Histology after explanation was examined to assess tissue integration (H&E) and collagen production (Massons Trichome). Immunohistochemistry was used to assess angiogenesis (CD3, α-SMA), immune response (CD45, CD68) and adipose formation (PPAR-γ). At 3-months PRP-ADSC-POSS-PCL scaffolds demonstrated significantly increased tissue integration and angiogenesis compared to PRP, ADSC and unmodified scaffolds (p

Background: Intra-articular injections of platelet-rich plasma to treat symptoms of knee osteoarthritis have been successfully used in young patients. However in most of these studies the control and test knees were present in different patients thus incorporating a large amount of bias in the results. Therefore, the present study was designed in which patients with bilateral osteoarthritis knee were included and platelet-rich plasma was administered in one knee and normal saline in another knee of same patient. Methods: 20 patients aged 30–65 years with bilateral osteoarthritis knees (ASA class I and II) of either gender were included in the study. Patients were randomized to receive platelet-rich plasma and normal saline in one of the two knees. The primary outcome was VAS and WOMAC score at 6 months after procedure. The secondary outcome included changes in joint stiffness, physical function, any adverse effects noted during the course of study. Results: The baseline VAS score in platelet-rich plasma knee was 8.4 ± 0.88 which improved significantly to 4.85 ± 2.48 (p

Introduction: Transforming growth factor-beta (TGF-β) is known as standard chondrogenic differentiation agent, even though it comes with undesirable side effects such as early hypertrophic maturation, mineralization, and secretion of inflammatory/angiogenic factors. On the other hand, platelet-rich plasma (PRP) is found to have a chondrogenic impact on mesenchymal stem cell proliferation and differentiation, with no considerable side effects. Therefore, we compared chondrogenic impact of TGF-β and PRP on adipose-derived stem cells (ADSCs), to see if PRP could be introduced as an alternative to TGF-β. Methods: Differentiation of ADSCs was monitored using a couple of methods including glycosaminoglycan production, miRNAs expression, vascular endothelial growth factor (VEGF)/tumor necrosis factor alpha (TNFα) secretion, alkaline phosphatase (ALP) and calcium content assays. Results: Accordingly, the treatment of differentiating cells with 5% (v/v) PRP resulted in higher glycosaminoglycan production, enhanced SOX9 transcription, and lowered TNFα and VEGF secretion compared to the control and TGF-β groups. Besides, the application of PRP to the media up-regulated miR-146a and miR-199a in early and late stages of chondrogenesis, respectively. Conclusion: PRP induces in vitro chondrogenesis, as well as TGF-β with lesser inflammatory and hypertrophic side effects.

Relevance. Owing to its controlling action on the inflammatory process, pain-relieving and reparative effects the RPR-therapy became quite demanded for treatment of certain types of tendinopathies specified by prevalence of degenerative process and poor reparative potential. Purpose of the study — to evaluate the efficiency of PRP-therapy in patients with tendinopathies of rotator cuff (RC) long head of biceps (LHB) tendons. Material and Methods. The paper presents the results of two-center prospective study for application of autologous platelet rich plasma in treatment of 122 patients: 53 men and 69 women aging 46.8±6.8 years who suffered RC tendinopathy (66%), subacromial impingement syndrome and RC tendinopathy (17%) and LHB tendinopathy (17%). Treatment outcomes were evaluated in 1, 3 and 6 months after PRP-therapy using various scales — VAS, UCLA , DASH, — and instrumental examination methods (US, MRI). Results. The authors observed statistically significant improvement in pain and functional scores in all three groups as compared to reported scores prior to PRP-therapy during 6 months follow up. During this period of evaluation, the scores of UCLA and DASH in patients with RC tendinopathy improved at 8.6 and 36.4 points, with subacromial impingement syndrome and RC tendinopathy — at 9.6 and 38.8 points, with LHB tendinopathy — at 11.5 and 44.1 point, respectively. The most notable reduction of pain syndrome by VAS was achieved in treatment of LHB tendinopathy (at 5.4 points) and RC tendinopathy (at 5.2 point). The highest average scores of satisfaction with treatment outcomes were reported in patients with RC tendinopathy (2.3) and LHB tendinopathy (2.2). MRI and ultrasound examinations after PRP-therapy demonstrated improved structure of RC and LHB tendons — decreased or eliminated swelling, areas of hypoechoic signal. Conclusion. PRP-therapy in patients with RC and LHB tendons and with subacromial impingement syndrome with RC tendinopathy significantly reduces severity of pain and improved the shoulder joint function with positive dynamics during 6 months follow up.

Objectives This study examined the effects of plasma-rich growth factors (PRGF) on accelerating bone regeneration/repair in fresh extraction sockets, and determined the quality and quantity of bone by assessing the bone density using cone-beam computed tomography (CBCT). Materials and methods Twenty patients, who had undergone bilateral extractions, were included in this study. In one extraction socket, PRGF was used and covered with an autologous fibrin plug. Nothing was used in the opposite side extraction socket. Thirteen weeks post extraction, the level of bone regeneration was evaluated on both sides with CBCT. Results At the end of the study, the mean bone density according to the Hounsfield units (HU) in the control group and PRGF group was 500.05 HU (type III bone type) and 647.95 HU (type II bone type), respectively. Conclusion This study recommends the use of PRGF in post extraction sites to accelerate the rate of bone regeneration and improve the quality of regenerated bone. The technique to process PRGF was simple compared to previously mentioned techniques used for platelet-rich plasma (PRP) preparation. PRP preparation requires a two-cycle centrifugation procedure, leading to a longer processing time.

BACKGROUND Platelet-rich plasma (PRP) is an increasingly used biologic adjunct for muscle injuries, as it is thought to expedite healing. Despite its widespread use, little is known regarding the mechanisms by which PRP produces its efficacious effects in some patients. AIM To clarify the effects of PRP on muscular pathologies at the cellular and tissue levels by evaluating the basic science literature. METHODS A systematic review of PubMed/MEDLINE and EMBASE databases was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist. Level III in vivo and in vitro studies examining PRP effects on muscles, myocytes and/or myoblasts were eligible for inclusion. Extracted data included PRP preparation methods and study results. RESULTS Twenty-three studies were included (15 in vivo, 6 in vitro, 2 in vitro/in vivo). Only one reported a complete PRP cytology (platelets, and red and white blood cell counts). Five in vitro studies reported increased cellular proliferation, four reported increased gene expression, and three reported increased cellular differentiation. Five in vivo studies reported increased gene expression, three reported superior muscle regeneration, and seven reported improved histological quality of muscular tissue. CONCLUSION The basic science literature on the use of PRP in muscle pathology demonstrates that PRP treatment confers several potentially beneficial effects on healing in comparison to controls. Future research is needed to determine optimal cytology, dosing, timing, and delivery methods of PRP for muscle pathologies.

BackgroundSurgical treatment of full-thickness rotator cuff (RC) tears is associated with generally good results. There is no consensus regarding treatment of partial thickness tears that fail conservative treatment. The purpose of this study was to look at the efficacy and confirm the safety of dual injection PRP into the shoulder of patients with rotator cuff pathology who have failed conservative treatment with followup to two years.MethodsSeventy-one shoulders with MRI confirmed, rotator cuff pathology who failed conservative treatment, had dual PRP injection into the rotator cuff. Global improvement, Quick DASH and VAS scores were collected at 6, 12, and 24 months after treatment and comparison of means was used to analyze changes.ResultsNo adverse events were seen in any patient. Based on global rating scores positive results were seen in 77.9 % of patients at 6 months, 71.6 % at 1 year, and 68.8 % of patients at 2 years. Mean VAS scores improved from 50.2 [CI 44.4–56.0] pre-injection to 26.2 [CI 19.5–32.9] at 6 months, 22.4[CI 16.1–28.7] at 1 year and 18.2 [CI 12.3–24.1] at 2 years (p 50 % partial tear group had the best overall improvement based on Global Rating scores while those in the tendinitis group had the poorest outcomes.ConclusionsPRP injection is a safe and effective treatment for RC cuff injury in patients who have failed conservative treatment of activity modification and physical therapy without deterioration of results two years after treatment. Better results are obtained with greater structural tendon damage than in shoulders with inflammation without structural damage.Trial registrationThis is not a clinical trial.

Introduction Current non-invasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Though these therapies work well for many, a subset of patients have contraindications or are unsatisfied with these options. Restorative therapies for ED are a new frontier of treatments focused on regenerating diseased tissue and providing a potential “cure” for ED. Aim The aim of this position statement is to examine existing clinical trial data for restorative therapies and identify elements that require further research before widespread adoption. Methods A literature review was performed to identify all clinical trials performed with regenerative therapy for ED. This includes treatments such as stem cell therapy (SCT), platelet rich plasma (PRP), and restorative related technologies like low-intensity shockwave therapy (LiSWT). Main Outcome Measures Most clinical trials in restorative therapies were assessed for safety, feasibility, or efficacy. This included recording adverse events, changes in sexual function and erectile function questionnaires, and diagnostics measures. Results To date there is an absence of robust clinical data supporting the efficacy of restorative therapies regarding ED, though technologies such as LiSWT have established relative safety. Conclusions Restorative therapies are a promising technology that represents a new frontier of treatment geared towards reversing disease pathology rather than just treating symptoms. However, current published clinical studies are limited. Future work needs to be adequately powered, multi-center, randomized, sham/placebo-controlled trials in well-characterized patient populations to ensure safety and demonstrate efficacy. Until these studies are done, restorative therapies should be reserved for clinical trials and not offered in routine clinical practice.

Background Osteoarthritis (OA) is a degenerative disease commonly affecting the knee joints. It affects patients socially, psychologically and economically and rates of the disease have been increasing due to obesity and old age. Regardless of choosing a medically conservative approach, it is a challenge in the long term to provide OA patients efficient treatment with minimal side effects and long-term efficiency. Platelet-rich plasma (PRP) is a convenient, low-cost and affordable treatment technique used in treating knee OA with encouraging efficient and safe outcomes. In this study we will investigate the effect of PRP on knee OA. Methods This is a prospective cohort study involving 252 patients with different OA grades. The Kellgren and Lawrence (K&L) system was used in classifying the affected knee by degenerative cartilage lesions as well as early and severe OA. All patients with a diagnosis of knee OA were screened in every visit before the injection, the pain was assessed by the 0-10 Numeric Rating Scale (NRS), and knee range of motion including flexion and extension was assessed by goniometer. Follow-up appointments were done on three-month intervals for a total of three visits for evaluation. Injection of PRP was given to all the patients with a maximum of four injections. The results were evaluated statistically according to the total number of follow-up visits. Results In grade II patients, the pain improved with the visits and the maximum improvement in flexion degree was noticed in patients who came for a total of three follow-up visits. In grade III patients, the most improvement in pain was in patients who came for three follow-up visits, while the most improvement in flexion degree was in patients who came for a total of two follow-up visits. Patients with grade IV who came for three follow-up visits showed the most improvement in pain and degree of flexion. Conclusions Intra-articular injections gave significant pain and flexion improvement in grades II, III and IV in OA patients, especially with multiple injection in the short-term follow-up. As a result, recommendation of repeated multiple injections up to four times is efficient in providing long time relief in knee OA.

Introduction: Prolonged inflammation after tracheal injury invariably results in a degree of stenosis. The topical application of platelet-rich plasma (PRP) and human amniotic fluid-derived cell culture medium (ACCM) have been shown to promote wound healing. The effects of PRP and amniotic cell culture medium (Gibco AmnioMAX - II ) were investigated in a rat model through morphometric, histological, and biochemical parameters. Material & Methods: Thirty-two male Sprague Dawley rats were included in the study: 4 rats provided for the preparation of PRP. Three groups of 7 rats were divided into PRP and ACCM groups, a control and a sham group respectively. A transverse incision on the ventral aspect of the third trachea spanning half of the tracheal circumference was performed. The incision was repaired with 7/0 polypropylene in the sham group. In the control group, 0.5 ml saline solution was applied on to the repaired injury site. In the other two groups, 0.5 mL PRP or ACCM were applied topically on the tracheal repair. Tissue samples were harvested 30 days after surgery for morphometric measurements and biochemical analyses for oxidative stress markers, IL-1beta, IL-6, and VEGF. Connective tissue thickness was evaluated histologically. Statistical analysis included the Mann-Whitney U and Kruskal Wallis tests. Results: A notable difference was detected (P = 0,025) in cartilage segment length measurements of the trachea between the ACCM group and the sham and control groups (P < 0.03). A significant difference was found in the analysis of TAS, TOS, and OSI values between the study groups and the control and sham groups (P < 0.005). There were also differences in IL1-beta and IL-6 levels between ACCM and PRP groups (P < 0.05). For the same parameters, the differences were significant between the PRP and, sham and control groups (P = 0,004 and P = 0,002 respectively), and between the ACCM and, sham and control groups (P = 0,003 and P = 0,002 respectively). VEGF values demonstrated a significant difference between the PRP and sham group (P = 0,002), and between ACCM and sham/control groups (p=0,002 for both), the highest VEGF value was in ACCM group while the lowest value was in the sham group. In the histological assessment of connective tissue, a significant difference was observed between ACCM and the other groups. Conclusion: Amniotic fluid-derived cell culture medium shows less oxidative stress status than the other applications. ACCM is more effective on inflammatory and angiogenetic processes. Connective tissue thickness results were consistent with those biochemical and morphologic results. Additionally, a significant difference was observed in histological data between ACCM and PRP. Overall, ACCM proved to be efficient on tracheal healing. These effects can be attributed to the abundance of growth factors in both PRP and amniotic fluid-derived cell culture medium (ACCM).

Osteoarthritis of the knee (OAK) is a chronic degenerative disease and progresses with an imbalance of cytokines and macrophages in the joint. Studies regarding the use of platelet-rich plasma (PRP) as a point-of-care treatment for OAK have reported on its effect on tissue repair and suppression of inflammation but few have reported on its effect on macrophages and macrophage polarization. Based on our clinical experience with two types of PRP kits Cellaid Serum Collection Set P type kit (leukocyte-poor-PRP) and an Autologous Protein Solution kit (APS leukocyte-rich-PRP), we investigated the concentrations of humoral factors in PRPs prepared from the two kits and the effect of humoral factors on macrophage phenotypes. We found that the concentrations of cell components and humoral factors differed between PRPs purified using the two kits, APS had a higher concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte-derived macrophages and M1 polarized macrophages revealed that PRPs suppressed M1 macrophage polarization and promoted M2 macrophage polarization. This research is the first to report the effect of PRPs purified using commercial kits on macrophage polarization.

BACKGROUND Anal fissure is one of the most common benign anal disorders, and medical treatments play an important role in its management. OBJECTIVE The purpose of this study was to investigate the short-term effects and success of platelet-rich plasma in the treatment of chronic anal fissure. DESIGN The study is a 2 parallel group, randomized, controlled clinical trial. SETTINGS The study was performed in 2 tertiary university hospitals. PATIENTS Forty-four patients with chronic anal fissure were randomly assigned to platelet-rich plasma treatment or control group. Presenting symptoms and pain scores were recorded on enrollment. The control patient self-administered topical glyceryl trinitrate. Platelet-rich plasma was injected locally in the intervention group followed by self-administered glyceryl trinitrate. MAIN OUTCOME MEASURES The primary outcome measure is a reduction in pain scores. RESULTS On day 10 and 1 month after treatment, the mean pain score was significantly lower in the patients treated with platelet-rich plasma than in the controls (p = 0.005 and p < 0.005). By 1 month after treatment, the mean pain score declined by 5.7 points in the platelet-rich plasma-treated group compared with a 4.1 mean pain score decline in the control group (mean difference:1.6 points (95% CI, 0.3-2.9)). According to the repeated-measures analyses, pain scores decreased in both groups, but the decrease in the treatment group was statistically higher than in the control group (p < 0.001). Complete epithelialization and recovery rates were significantly higher in the platelet-rich plasma group than in controls at all follow-up times, with p values ranging from 0.034 to

Background: In the last decade, regenerative therapies have become one of the leading disease modifying options for treatment of knee osteoarthritis (OA). Still, there is a lack of trials with a direct comparison of different biological treatments. Our aim was to directly compare clinical outcomes of knee injections of Bone Marrow Aspirate Concentrate (BMAC), Platelet-rich Plasma (PRP), or Hyaluronic acid (HA) in the OA treatment. Methods: Patients with knee pain and osteoarthritis KL grade II to IV were randomized to receive a BMAC, PRP, and HA injection in the knee. VAS, WOMAC, KOOS, and IKDC scores were used to establish baseline values at 1, 3, 6, 9, and 12 months. All side effects were reported. Results: A total of 175 patients with a knee osteoarthritis KL grade II-IV were randomized, 111 were treated with BMAC injection, 30 with HA injection, and 34 patients with PRP injection. There were no differences between these groups when considering KL grade, BMI, age, or gender. There were no serious side effects. The mean VAS scores after 3, 7, 14, and 21 days showed significant differences between groups with a drop of VAS in all groups but with a difference in the BMAC group in comparison to other groups (p &lt, 0.001). There were high statistically significant differences between baseline scores and those after 12 months (p &lt, 0.001) in WOMAC, KOOS, KOOS pain, and IKDC scores, and in addition, there were differences between these scores in the BMAC group in comparison with other groups, except for the PRP group in WOMAC and the partial IKDC score. There were no differences between the HA and PRP groups, although PRP showed a higher level of clinical improvement. Conclusions: Bone marrow aspirate concentrate, Leukocyte rich Platelet Rich Plasma, and Hyaluronic acid injections are safe therapeutic options for knee OA and provide positive clinical outcomes after 12 months in comparison with findings preceding the intervention. BMAC could be better in terms of clinical improvements in the treatment of knee OA than PRP and HA up to 12 months. PRP provides better outcomes than HA during the observation period, but these results are not statistically significant. More randomized controlled trials and high quality comparative studies are needed for direct correlative conclusions.

Introduction Hyperlipidemia is associated with an increased risk of erectile dysfunction (ED) mediated by endothelial damage. Platelet-rich plasma (PRP) contains numerous angiogenic growth factors. Currently, evidence supporting the use of PRP for ED treatment is limited. Aim We investigated PRP in a rat model of hyperlipidemia-associated ED. Methods Thirty 2-month-old male Sprague–Dawley rats were randomly divided into 3 groups. 20 rats were fed a high-fat diet for 5 months and were randomly divided into 2 groups: (i) rats in the H group received supernatant injection into the corpus cavernosum weekly for 4 weeks; (ii) rats in the H + PRP group received PRP injection into the corpus cavernosum weekly for 4 weeks. 10 rats were fed a standard diet for 5 months and received supernatant injection into the corpus cavernosum weekly for 4 weeks (N group). 7 days after the 4th injection, all rats underwent erectile function testing and then euthanasia. Main outcome measures Erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP). Serum and penile tissue were collected for metabolic variable assessment and histochemical examination, respectively. Results Intracavernous pressure/MAP and area under the curve/MAP ratios were significantly higher in the N and H + PRP groups than in the H group. Insulin-like growth factor-1, brain-derived neurotrophic factor, and vascular endothelial growth factor levels were significantly higher in the H + PRP group than in the N and H groups. Corporal neuronal nitric oxide synthase, endothelial nitric oxide synthase, and endothelial cells were weakly expressed in the H group compared with the N and H + PRP groups. Intracorporal oxidative stress and apoptotic index were significantly higher in the H group than in the N and H + PRP groups. Conclusions This preclinical evidence suggests that clinical trials of PRP in men with ED should be considered. PRP may play a role in ED management.

The prospect of ovarian rejuvenation offers the tantalising prospect of treating age-related declines in fertility or in pathological conditions such as premature ovarian failure. The concept of ovarian rejuvenation was invigorated by the indication of the existence of oogonial stem cells (OSCs), which have been shown experimentally to have the ability to differentiate into functional follicles and generate oocytes; however, their clinical potential remains unknown. Furthermore, there is now growing interest in performing ovarian rejuvenation in situ. One proposed approach involves injecting the ovary with platelet rich plasma (PRP). PRP is a component of blood that remains after the in vitro removal of red and white blood cells. It contains blood platelets, tiny anucleate cells of the blood, which are responsible for forming athrombus to prevent bleeding. In addition, PRP contains an array of cytokines and growth factors, as well as a number of small molecules.The utility ofPRP has been investigatedin a range of regenerative medicine approaches and has been shown to induce differentiation of a range of cell types, presumably through the action of cytokines. A handful ofcasereports have described the use of PRP injections into the ovaryin the human, and while these clinical data report promising results, knowledge on the mechanisms and safety of PRP injections into the ovary remain limited.In this article, we summarise some of the physiological detail of platelets and PRP, before reviewing the existing emerging literature in this area. We then propose potential mechanisms by which PRP may be eliciting any effects before reflecting on some considerations for future studies in the area. Importantly, on the basis of our existing knowledge, we suggest that immediate use of PRP in clinical applications is perhaps premature and further fundamental and clinical research on the nature of ovarian insufficiency, as well as the mechanism by which PRP may act on the ovary, is needed to fully understand this promising development.

Introduction Venous ulcers are the most common type of leg wounds (80%) and the main cause is chronic venous insufficiency. Autologous platelet-rich plasma (PRP) is a potential wound healing treatment due to its great variety of growth factors. The aim of this study was to describe in a case series the results of poor-leukocyte PRP (P-PRP) or saline for the treatment of chronic non-healing ulcers of the lower extremity. Methods Eight patients were treated according to the topical therapy: saline solution or P-PRP gel. All patients used double compression stocks and were assisted by a vascular practitioner for up to 12 months or until wound healing. The treatment was performed weekly with cleaning of the affected area, macroscopic evaluation (area measurement and photos) and P-PRP or saline application, and closure with Tegaderm®. Trial Registration: Retrospectively approved by Brazilian Clinical Trials, register number RBR-7zhgb3 ( http://www.ensaiosclinicos.gov.br/rg/RBR-7zhgb3/ ). Results All patients showed signs of wound healing with a reduction in wound size and ulcer numbers, but more evident with P-PRP application. Conclusions The results suggested that P-PRP presented a better result when compared to saline solution in the healing process of long clinical course chronic venous ulcers, when associated to compressive stocks and topical care.

Mesenchymal stem cells (MSCs) have been recently introduced in veterinary medicine as a potential therapeutic tool for several pathologies. The large-scale in vitro expansion needed to ensure the preparation of a suitable number of MSCs for clinical application usually requires the use of xenogeneic supplements like the fetal bovine serum (FBS). The substitution of FBS with species-specific supplements would improve the safety of implanted cells, reducing the risk of undesired immune responses following cell therapy. We have evaluated the effectiveness of canine adipose tissue-derived stromal vascular fraction (SVF) and MSCs (ADMSCs) expansion in the presence of canine blood-derived supplements. Cells were cultured on traditional plastic surface and inside a 3D environment derived from the jellification of different blood-derived products, i.e., platelet-poor plasma (PPP), platelet-rich plasma (PRP), or platelet lysate (PL). PPP, PRP, and PL can contribute to canine ADMSCs in vitro expansion. Both allogeneic and autologous PPP and PL can replace FBS for ADMSCs culture on a plastic surface, exhibiting either a similar (PPP) or a more effective (PL) stimulus to cell replication. Furthermore, the 3D environment based on homospecific blood-derived products polymerization provides a strong stimulus to ADMSCs replication, producing a higher number of cells in comparison to the plastic surface environment. Allogeneic or autologous blood products behave similarly. The work suggests that canine ADMSCs can be expanded in the absence of xenogeneic supplements, thus increasing the safety of cellular preparations. Furthermore, the 3D fibrin-based matrices could represent a simple, readily available environments for effective in vitro expansion of ADMSCs using allogeneic or autologous blood-products.

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0&ndash, 2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations &ge, 0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.

Background: Chronic leg ulcerations are associated with Haemoglobin disorders, Type2 Diabetes Mellitus, and long-term venous insufficiency, where poor perfusion and altered metabolism develop into a chronic inflammation that impairs wound closure. Skin equivalent organotypic cultures can be engineered in vitro to study skin biology and wound closure by modelling the specific cellular components of the skin. This study aimed to develop a novel bioactive platelet-rich plasma (PRP) leukocyte depleted scaffold to facilitate the study of common clinical skin wounds in patients with poor chronic skin perfusion and low leukocyte infiltration. A scratch assay was performed on the skin model to mimic two skin wound conditions, an untreated condition and a condition treated with recombinant tumour necrotic factor (rTNF) to imitate the stimulation of an inflammatory state. Gene expression of IL8 and TGFA was analysed in both conditions. Statistical analysis was done through ANOVA and paired student t-test. P, Results: A skin model that consisted of a leukocyte-depleted, platelet-rich plasma scaffold was setup with embedded fibroblasts as dermal equivalents and seeded keratinocytes as multi-layered epidermis. Gene expression levels of IL8 and TGFA were significantly different between the control and scratched conditions (p, peer-reviewed

Objective Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSC) injections are non-surgical treatments for knee osteoarthritis (OA). The purpose of this study is to assess the effectiveness of serial PRP with or without ADSC injections in the treatment of refractory OA of the knee. Design Patients who failed to achieve pain relief with conventional non-surgical treatments, with Kellgren-Lawrence grade 3 or 4 knee OA, were recruited from a private outpatient clinic. Over 67 patients were elected to receive serial PRP injections and 22 patients were elected to receive an ADSC+PRP injection. These patients completed Western Ontario and McMaster Universities Arthritis Index (WOMAC) surveys prior to each treatment and at follow-up appointments. These surveys were retrospectively reviewed to assess changes in functional status and pain over time. Results Twenty-nine patients from the PRP group and eight patients in the ADSC+PRP group had adequate follow-up for inclusion in the analysis. The PRP group had an improvement in WOMAC scores by 34.30%, 60.2%, and 58.5% for patients reporting at 1-3, 4-6, and >6 months of follow-up. The ADSC+PRP group experienced an improvement of 51% at an average of 4.66 months of follow-up. Conclusions Serial PRP injections and a single ADSC+PRP injection yield improved and sustained functional outcome scores for patients with severe, refractory OA of the knee. Future studies should consider consistent orthobiologic preparation protocols to ensure reproducibility.

Platelet rich plasma contains a collection of growth factors, and an optimal formulation, named O-rPRP, contains the highest possible concentration of growth factors. Purpose Challenging the healing power of O-rPRP in a high-galactose diet-induced premature ovarian insufficiency (POI) experimental rat model. Methods Rats were divided into four groups of ten rats each and treated for four week as follows; 1) the control group, fed with normal diet and received intraperitoneal (i.p.) injection of PBS once/week; 2) the POI group, fed with galactose diet (50%) and received PBS (i.p.) once/week; 3) the POI/O-rPRP group, fed a 50% galactose diet and received O-rPRP (i.p.) once/week; 4) the O-rPRP group (negative control), fed with a normal diet and received O-rPRP (i.p.) once/week. The levels of galactose, follicle stimulating hormone, 17 β-estradiol, anti-mullerian hormone and inhibin B were measured in serum samples. Western blotting and quantitative real-time PCR assays were employed to investigate the levels of miR-223, β1 integrin, p70S6k and MCL-1 in ovarian tissues. Results After O-rPRP treatment, β1 integrin expression was enhanced, and miR-223 expression was decreased. Unlike the untreated galactose group, in the group treated with O-rPRP, p70S6k and MCL-1 expression levels were increased, indicating that the mTOR growth signaling pathway was active and that apoptosis was inactive. After the introduction of O-rPRP, the number of follicles and the follicular maturation improved, which was consistent with the improvement of inhibin B levels and subsequent inhibition of FSH. Conclusion O-rPRP inhibited galactose-induced excessive atresia and provided an overall protective effect on the ovarian follicles., Alternative medicine; Regenerative medicine; Reproductive hormone; Reproductive system; Toxicology; Cell biology; Apoptosis; Galactosemia; mTOR; Ovarian insufficiency; Platelet rich plasma.

Aims For cementless implants, stability is initially attained by an interference fit into the bone and osteo-integration may be encouraged by coating the implant with bioactive substances. Blood based autologous glue provides an easy, cost-effective way of obtaining high concentrations of growth factors for tissue healing and regeneration with the intention of spraying it onto the implant surface during surgery. The aim of this study was to incorporate nucleated cells from autologous bone marrow (BM) aspirate into gels made from the patient’s own blood, and to investigate the effects of incorporating three different concentrations of platelet rich plasma (PRP) on the proliferation and viability of the cells in the gel. Methods The autologous blood glue (ABG) that constituted 1.25, 2.5, and 5 times concentration PRP were made with and without equal volumes of BM nucleated cells. Proliferation, morphology, and viability of the cells in the glue was measured at days 7 and 14 and compared to cells seeded in fibrin glue. Results Overall, 2.5 times concentration of PRP in ABG was capable of supporting the maximum growth of cells isolated from the BM aspirate and maintain their characteristics. Irrespective of PRP concentration, cells in ABG had statistically significantly higher viability compared to cells in fibrin glue. Conclusion In vitro this novel autologous gel is more capable of supporting the growth of cells in its structure for up to 14 days, compared to commercially available fibrin-based sealants, and this difference was statistically significant. Cite this article: Bone Joint Res 2020;9(7):402–411.

Ovarian insufficiency is described as a multifaceted issue typically encountered in the field of assisted reproduction. The three main identified diagnoses of ovarian insufficiency include premature ovarian failure (POF), poor ovarian response (POR), and advanced maternal age (AMA). Patient heterogeneity in the era of individualized medicine drives research forward leading to the emergence of novel approaches. This plethora of innovative treatments in the service of adequately managing ovarian insufficiency is called to undertake the challenge of addressing infertile patients exploring their reproductive options. This review provides an all-inclusive presentation and critical analysis on novel treatments that have not achieved routine clinical practice status yet, but have recently emerged as promising. In light of the lack of randomized controlled trials conveying safety and efficiency, clinicians are left puzzled in addressing the “how” and “for whom” these approaches may be beneficial. From ovarian injection employing platelet-rich plasma (PRP) or stem cells to artificial gametes and ovaries, ovarian transplantation, and mitochondrial replacement therapy, this descriptive review provides insight toward assisting the practitioner in decision making regarding these cutting-edge treatments. Biological mechanisms, invasiveness levels, efficiency, as well as possible complications, the current status along with bioethical concerns are discussed in the context of identifying future optimal treatment.

Background: Platelet rich plasma (PRP) is used extensively in equine regenerative medicine. Differences in preparation protocols give rise to significant variability in the cellular composition of PRP making it very difficult to establish a standard of care in the field. This study aimed to optimize the preparation protocol for leukocyte-reduced PRP (P-PRP).Methods: Blood (100 mL) was collected from horses (n = 5) and divided into 2 purple top EDTA tubes and 6 (15 mL) double syringesa with a final concentration of 10% acid citrate dextrose anticoagulant. Six double syringesa were collected from each horse; PRP samples were prepared in duplicate and centrifuged at 1,100 rpm (188 × g), 1,300 rpm (263 × g), or 1,500 rpm (350 × g). Duplicates were subjected to +/– braking at the end of centrifugation. The total volume of PRP generated was measured and divided into thirds. Each third (top, middle, and bottom) were drawn off separately using the inner (6 mL syringe) and placed in purple top EDTA tubes. Automated complete blood counts were performed on all peripheral whole blood and PRP samples.Results: The concentration of leukocytes was higher in the bottom layer of PRP compared to the top and middle layers (p < 0.0001). The concentration of platelets was slightly lower in the bottom layer of PRP than the middle layer (p = 0.02). Centrifugation braking increased the leukocyte concentration in the top (p = 0.03) and middle layers of PRP (p = 0.001). Centrifugation rate had no effect on the cellular composition of PRP (p = 0.1–0.6).Conclusions: Because layer of plasma affected both platelet and leukocyte concentrations in PRP, the most important modification for the current single spin, double syringe, plasma based PRP preparation protocols is to exclude the bottom 1/3 layer of PRP.

The aim of the study was morphological substantiation of clinical efficacy of platelet rich plasma (PRP) in the treatment of patients with androgenetic alopecia (AGA). Materials and Methods: The study included 25 men aged from 20 to 43 years. AGA degree II-IV on the Hamilton-Norwood scale was diagnosed in 23 (92%) patients and degree I in 2 patients. All patients received intradermal injections of PRP. The course of treatment consisted of 4 procedures with an interval of 4 weeks between each procedure. The clinical efficacy of the therapy was evaluated by the dynamics of morphometric indicators of hair growth. The morphological analysis included an assessment of indicators in horizontal sections and was carried out at 4 levels: at the level of subcutaneous adipose tissue, sweat glands, sebaceous glands, and mouths of hair follicle (HF). Sections were stained with H&E. Histological examination was performed before and after treatment. Against the background of treatment with PRP, hair density increased by 12% (P=0.000), average hair diameter by 12% (P=0.002), and the share of vellus and telogen hair decreased by 17% (P=0.002) and 16% (P=0.028), respectively. At the same time, the amount of anagen hair in relation to telogen hair increased by 18% (P=0.016). Histologically, the increase in hair density was accompanied by a significant increase in the number of HF at the mouth level (∆+96%, P=0.004) and at the level of sweat glands (∆+54%, P=0.037), as well as a tendency for their number to increase at the level of the sebaceous glands. These increases were combined with a significant decrease in the proportion of telogen hair (∆-43%, P=0.023) and vellus hair (∆-29%, P=0.037). Conclusion: The positive clinical effect of PRP therapy is due to significant morphofunctional changes in hair follicles.

In this study efficiency of platelet rich plasma (PRP) and zinc oxide on full thickness wounds created on rabbits was researched. This study conducted on 24 New Zealand rabbits divided 2 groups. A circular of 1.5 × 1.5 cm (2.5 cm2) full thickness skin wound was created under the general anesthesia. 1 ml PRP (5.503106/mm3) was applied to the one of the wounds subcutaneously. To the other wound 1 mm3 zinc oxide ointment was applied once a day during the study. Wound contraction rates were measured, biopsy materials were collected and evaluated macroscopically and histopathologically postoperatively 3rd, 7th and 15th days. As a result it is determined that PRP and zinc oxide accelerated wound contraction rates between the groups were determined as 3rd day p = 0.007, 7th day p = 0.0002 and 15th day p = 0.002., Highlights • Wound healing is inborn to all species and is the biologic procedure by which the body repairs itself after injury, whichever it be traumatic, complicated, infected and/or surgical. • Platelet rich plasma (PRP) gel is measured to be progressive wound treatment for acute and chronic wounds. PRP gel has mainly been applied to improve or accelerate healing of wound. • Zinc is a vital trace element in the human body and its significance in wellbeing and infection is valued. Zinc deficiency of genetic or dietary cause can prompt neurotic, pathologic and physiological changes and deferred wound healing. • Topical treatment with autologous PRP can be used as clinical therapy and can enhance tissue healing and enhanced angiogenesis compared to zinc oxide treatments.

AIM To determine if topical application of platelet-rich plasma (PRP) to diabetic foot ulcers (DFUs) results in superior healing rates. METHODS A systematic review was registered with PROSPERO and performed using PRISMA guidelines. Level I-IV investigations of topical PRP application in DFUs were sought in multiple databases including: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms used were “platelet rich plasma”, “diabetes”, “ulcers”, and “wound”. The Modified Coleman Methodology Score (MCMS) was used to analyze study methodological quality. Study heterogeneity and a mostly non-comparative nature of evidence precluded meta-analysis. Only the outcome measurements used by more than 50% of the studies were included in the data synthesis to increase power of the measurement over that of individual studies. A weighted mean of healing rate per week between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance. RESULTS One thousand two hundred and seventeen articles were screened. Eleven articles (322 PRP subjects, 126 controls, PRP subject mean age 58.4 ± 7.2 years, control mean age 58.7 ± 5.9 years) were analyzed. Six articles were level II evidence, four were level III, and one article was level IV. The mean MCMS was 61.8 ± 7.3. Healing rate was significantly faster with PRP application compared to controls (0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P < 0.001). Mean heal time to > 90% of the original ulcer area was 7.8 ± 2.7 wk and 8.3 ± 3.7 wk for patients in the PRP group and control groups, respectively (P = 0.115). There were significantly lower adverse effects reported with PRP application compared to controls (7 wound infections, 1 contact dermatitis vs 14 wound infections, 1 maceration; P < 0.001). CONCLUSION The topical application of PRP for DFUs results in statistically superior healing rates and lower complication rates compared to controls.

Background Platelet-rich plasma (PRP) is an autologous product derived from whole blood through the process of gradient density centrifugation. Autologous PRP, with growth factors up to 8 times that of normal serum, has been shown to be safe and effective in promoting natural processes of wound healing. Our study aims to examine the effect of combining the fat graft with PRP in myringoplasty procedures indicated for TMP secondary to chronic suppurative otitis media (CSOM) and whether it can significantly promotes Tympanic membrane (TM) healing. Methods This prospective study included forty patients, presenting with dry tympanic membrane secondary to tubo-tympanic CSOM. Half the patients underwent fat graft Myringoplasty with PRP application (group A), while others served as control and received the fat graft only, without PRP (group B). Results In group A, eighteen cases (90%) significantly showed an intact tympanic membrane, while Eleven cases (55%) were successful in group B. P=0.044. Conclusion Topical autologous PRP application during fat plug Myringoplasty is highly successful with no reported postoperative infections and minimal morbidity.

Made available in DSpace on 2018-12-11T16:55:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-10-01 Objectives: To evaluate alterations from different therapies in muscular injury using the Fractal Dimension (FD) method. Methods: 35 animals were allocated in Control Group (C), Injury Control Group (IC), Injury Low Level Laser Therapy Group (ILT), Injury Platelet Rich Plasma Group (IP), and Injury LLLT and PRP Group (ILP). The animals suffered a stretch injury in gastrocnemius muscle and after that IP and ILP groups received PRP application. The ILT and ILP groups received daily LLLT applications for seven days. After seven days the animals were euthanized and the gastrocnemius muscle removed and frozen. The muscles were stained with Hematoxylin and Eosin (HE) and Picrosirius Red, for observation of the morphology of the injury and semi-quantitative and quantitative analysis through the Fractal Dimension (FD) method. Results: In the qualitative and semi-quantitative analysis, in relation to IC group, the ILT presented a reduction in rounded fibers and the IP in angular fibers. The ILP group demonstrated a reduction in both polymorphic fibers and inflammatory infiltrate. The FD of the muscles stained with HE was higher in the groups that suffered the injury when compared to the C group (p < 0.05); the FD of the collagen demonstrated no statistical difference between the groups. Conclusion: Both treatments were able to accelerate injury repair, and the association of both presented better results than the isolated applications. However, the FD method showed no sensitivity to differentiate the treatments, either in the histological aspects or the injury in collagen. Universidade Estadual de Campinas (UNICAMP) Programa de Pós-graduação em Ciências da Cirurgia Universidade de São Paulo (USP) Programa de Pós-graduação em Ciências Morfofuncionais Universidade Estadual Paulista (UNESP) Departamento de Fisioterapia Universidade Estadual Paulista (UNESP) Departamento de Fisioterapia

Background. Surgical removal of mandibular third molars results in pain, swelling and bony defects, causing prolonged postoperative recovery. The growth factors present in platelet-rich plasma (PRP) can accelerate the healing, thereby shortening postoperative recovery period. This study was undertaken to evaluate the role of PRP in postoperative socket healing, pain, swelling and bone regeneration following surgical removal of impacted mandibular third molars. Methods. The present case‒control study was conducted on 20 patients with identical bilateral mandibular third molar impaction. PRP was placed randomly on one side of 3rd molar extraction socket and the contralateral side was used as control. Evaluation of soft tissue healing, pain, swelling and radiologic bone density was carried out. Results. Soft tissue healing was better in the PRP compared to the control site. Immediate postoperative assessment of pain scores showed no significant difference between the two groups (Mann-Whitney U test). On the 7th day, pain scores were lower in case site compared to the control site. Measurement of swelling on the 1st, 3rd and 7th day showed statistically significant differences between the case and control sites (P

Disturbed or delayed healing remains one of the most serious fracture-related complications, despite bone capacity for internal regeneration and reabsorption. Considerable progress in the understanding and treatment of fractures has been noted. The aim of our study was to evaluate treatment outcome in patients (smokers and non-smokers) with post-traumatic pseudoarthrosis. Hypothesis Determinate when administration of growth factors is most beneficial, and whether it accelerates bone union. Material and methods The study included patients treated for post-traumatic pseudoarthrosis resulting from multiple bone fractures. The study group and controls were further subdivided into: non-smokers, non-smokers >2 years after quitting, and smokers. Independent tests were performed for men and women. The study group, apart from other methods of treatment, received concentrated PRP (platelet-rich plasma) to aid the process of bone healing, or in cases of delayed healing confirmed by radiological assessment on follow-up visits. Results Mean time of fracture healing was 8 weeks for non-smokers and non-smokers >2 years after quitting, whereas in smokers the healing process was significantly prolonged (18 weeks in both, men and women). Conclusions The risk for infection is smaller in non-smokers as compared to smokers, with the latter being at an elevated risk for bone inflammation and delayed union.

Articular cartilage is avascular and aneural, and has limited capacity for self-regeneration when injured. Tissue engineering has emerged as a promising approach in repairing cartilage defects. To improve the therapy of cartilage healing, the present study investigated the efficacy of the combination of lentivirus-mediated bone morphogenetic protein-2 (BMP2) in bone marrow-derived stromal cells (BMSCs) and platelet-rich plasma (PRP) on cartilage and bone healing in a cartilage defect model using the rabbit knee. The BMSCs were harvested from New Zealand rabbits and transduced with lentivirus carrying BMP-2. Standard bone defects were introduced in the femoral groove of patellofemoral joints of 48 New Zealand rabbits. The cartilage defects were subjected to synthetic scaffold mosaicplasty with chitosan/silk fibroin/nanohydroxyapatite particles tri-component scaffolds soaked in BMSCs and PRP. After 16 weeks, the tissue specimens were assessed by micro-computed tomography (micro-CT) and macroscopic examination. The results showed that lentivirus-mediated BMP-2 and PRP increased the cell viability of the BMSCs, induced the expression of associated genes and enhanced osteogenic differentiation in vitro. In vivo, the expression of BMP-2 was observed for 16 weeks. The combination of BMP-2 and PRP treatment led to optimal results, compared with the other groups on micro-CT and gross observations. The results of the present study present a novel therapy using the lentivirus-mediated BMP-2 gene together with PRP for cartilage healing.

Platelet rich plasma (PRP) is popularly used in the horse industry to enhance regeneration of tissue injury that has limitation of blood supply. This study aimed to compare the methods for platelet rich plasma preparation since they has not been established yet. Blood was collected from six horses and platelets were concentrated by three different methods (2-step centrifugation, separated centrifugation and separated centrifugation using histopaque). Concentrated blood was analyzed using Advia hematology systems. In the result, separated centrifugation with histopaque showed the significantly lower number of red blood cells than other groups. The 2-step centrifugation showed the significantly higher number of white blood cells than other groups, while it contained the highest concentration of red blood cells among three groups. In the 2-step centrifugation, separated centrifugation and separated centrifugation with histopaque, platelets were concentrated 4.5, 5.3 and 5.6 times, respectively. And no significant difference of the platelet concentration between the three groups was found. This study demonstrated that separated centrifugation using histopaque was the best method for platelet rich plasma preparation because of the proper amount of platelets and the separation of red blood cells from platelet rich plasma.

Currently, the most actual problem in daily work of a surgeon is to get satisfactory results of the surgery, and to decrease the quantity of different complications, such as: recurrence of diseases, inflammatory and infection damage of operating wounds.The most difficult for surgery treatment are urological diseases associated with the decrease of tissue vascularization, which leads to common fibrosis and the prevalence of soft tissue scarring, consequences of the radiation therapy.Impaired wound healing is usually associated with lack of adequate blood supply, decrease of regenerative properties, increase of pro-inflammatory mechanisms. Platelet rich plasma is able to produce a lot of different growth factors, which stimulate neoangiogenesis, cytokines and сhemokines secretion, initialization of inflammatory cascade. These features lead to activation of regenerative mechanisms and growth of new blood vessels. In the present time, several forms of platelet rich plasma with different biological activity have been studied. The methods of its preparation and activation have been described. In this work the modern information of platelet rich plasma will be described in details.

Trombositlerhemostaz ve yara iyileşmesinde çok önemli bir rol oynamakta ve ihtiva ettikleribüyüme faktörleri ve sitokinler sayesinde rejeneratif tedavinin potansiyelhücreleri arasında yer almaktadırlar. Bu durum, rejeneratif tedavide, trombositve trombosit konsantrasyonlarına olan ilgiyi arttırmıştır. Geçmişten günümüzekadar çeşitli trombosit konsantrasyonları elde edilmiş ve bu ürünler tek başınaveya başka biomateryallerle kombine kullanıldığında, iyileşme sürecine olanolumlu katkıları görülmüştür. Trombosit konsantrasyonları, sert ve yumuşak dokuile ilgili cerrahi prosedürlerde kullanıldığında, içeriğinde bulunan yoğunsitokin ve büyüme faktörlerinin kontrollü salınımı sağlar. Bu durum doğal yaraiyileşme sürecini hızlandırmaktadır. Ayrıca, otojen kaynaklı olduklarındanherhangi bir immünolojik reaksiyon ve enfeksiyona yol açmamaları en önemliavantajlarıdır. Tam kan farklı devirlerde ve farklı sürelerde santrifüjedildiğinde içeriği birbirinden farklı olan trombosit kaynaklı ürünler eldeedilmiştir. PRP, PRGF, PRF ve CGF gibi ürünlere bakıldığında yeni keşfedilenher ürünün bir öncekine göre daha gelişmiş özellikleri olduğu görülmektedir. Bu derlemenin amacı; PRP, PRGF, PRF ve CGF gibitrombosit konsantrasyonlarının tarihsel gelişimi ve özellikleri hakkında bilgivermektir., Plateletsare playing a very important role in wound healing and hemostasis and are amongthe potential cells of regenerative therapy due to the growth factors andcytokines they contain. This has increased the interest in platelet andplatelet concentrates in regenerative therapy. Various platelet concentratesfrom the past to the present day were obtained, and when these products wereused alone or in combination with other biomaterials, positive contributions tothe healing process were observed. When platelet concentrates are used insurgical procedures involving hard and soft tissue, they provide controlledrelease of intense cytokines and growth factors in their contents. Thissituation is accelerating the natural wound healing process. In addition, theyare the most important advantages because they do not cause any immunologicalreaction and infection since they are autogenous. When whole blood iscentrifuged at different cycle and different times, platelet derived productswith different contents are obtained. Looking at the products such as PRP,PRGF, PRF and CGF, it is seen that each newly discovered product has moreadvanced characteristics than the previous one. The aim of review; platelet concentrate's such as PRP, PRGF,PRF, CGF give information about the historical development and properties.

Higher prevalence and growing burden of knee Osteoarthritis (OA) combined with recent safety concerns about pharmacological interventions has increased demand for new effective technologies for its management. Need of the hour is an innovative treatment alternative which may repair cartilage damage rather than just reduce symptoms of pain. Hyaluronic acid (HA) and PRP has been shown to relieve pain and symptoms as well as slow the progression of disease as stand-alone therapy. Treatment combining these modalities could be particularly hopeful owing to their positive and diverse interaction among themselves. Combinational treatment using both PRP and HA was performed on a series of 12 patients with early stage primary knee OA who fulfilled all the designated inclusion and exclusion criteria. All the patients were evaluated before and after treatment (1, 3, 6 and 12 months) by physical examination, assessment of VAS for pain, WOMAC, IKDC, KOOS and OKS to record the patient-reported improvement in pain, functionality and quality of life (QOL). 2-tailed Mann Whitney U Test was performed to assess the effect of treatment at different follow-up times of all the clinical scores. Whereas, Pearson correlation coefficient was done to evaluate the correlation between different clinical scores. For all tests, p < 0.05 was considered significant. All patients showed statistically significant improvement in all orthopedics scores evaluated. VAS score was improved significantly from 3.00 ± 0.49 at baseline to 1.57 ± 0.41 (p = 0.031) in Grade I and 3.60 ± 0.51 at baseline to 2.10 ± 0.29 (p = 0.031) in Grade II patients at 6 months’ follow-up respectively. Other scores followed similar trends with statistically significant improvement at 6 months’ follow-up which maintained throughout till end of the study period. All patients treated experienced strong functional improvement and substantial gains in pain relief, functionality and QOL. Hence our preliminary findings suggest that combined PRP and HA procedure is safe and potentially efficacious, which merits further investigation in large clinical settings and also in controlled clinical trials with long-term follow-ups. Focal Points Bench side: Platelet Rich Plasma (PRP) deliver a large pool of signalling proteins including growth factors and cytokines to the local milieu driving the tissue regeneration and repair mechanisms which when combined with high molecular weight cross-linked hyaluronan could bestow greater viscoelastic properties and alleviate the symptoms of osteoarthritis. Bedside: Osteoarthritis (OA) is a chronic degenerative disease and there is no cure for OA except medical management and partial/total knee replacement in advanced stage. PRP along with HA could have the therapeutic potential to promote cartilage regeneration and inhibit inflammation synergistically by decreasing the friction coefficient and minimizing wear. Community: The burden of OA on quality of life, disability and health care utilization is quite high. Combined PRP and HA could be an effective single-dose treatment modality restoring the functional activities and considerably reducing effective cost of the treatment. Governments and regulatory agencies: The technology to obtain PRP is FDA-approved and its safety and efficacy has been well established through several clinical studies. Regulatory agencies should consider the evidences put forth by the researchers and sanction grants to investigate in larger clinical settings and also in controlled trials with different ethnicities with long-term follow-ups.

Although platelet-rich plasma (PRP) is used as a source of growth factors in regenerative medicine, its effectiveness remains controversial, partially due to the absence of PRP preparation protocols based on the regenerative role of platelets. Here, we aimed to optimise the protocol by analysing PRP angiogenic and regenerative properties. Three optimising strategies were evaluated: dilution, 4 °C pre-incubation, and plasma cryoprecipitate supplementation. Following coagulation, PRP releasates (PRPr) were used to induce angiogenesis in vitro (HMEC-1 proliferation, migration, and tubule formation) and in vivo (chorioallantoic membrane), as well as regeneration of excisional wounds on mouse skin. Washed platelet releasates induced greater angiogenesis than PRPr due to the anti-angiogenic effect of plasma, which was decreased by diluting PRPr with saline. Angiogenesis was also improved by both PRP pre-incubation at 4 °C and cryoprecipitate supplementation. A combination of optimising variables exerted an additive effect, thereby increasing the angiogenic activity of PRPr from healthy donors and diabetic patients. Optimised PRPr induced faster and more efficient mouse skin wound repair compared to that induced by non-optimised PRPr. Acetylsalicylic acid inhibited angiogenesis and tissue regeneration mediated by PRPr; this inhibition was reversed following optimisation. Our findings indicate that PRP pre-incubation at 4 °C, PRPr dilution, and cryoprecipitate supplementation improve the angiogenic and regenerative properties of PRP compared to the obtained by current methods. Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Frechtel, Gustavo Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gutt, Susana. Hospital Italiano; Argentina Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina

Fish scale is rich in collagen type I and hydroxyapatite, resembling bone structure. It is readily available, cost effective and can compensate for the limitations of grafting methods such as unavailability, zoonotic disease transmission, and high cost. The aim of this study was to evaluate in vivo the fish scale potential and the possible synergistic effect of platelet rich plasma (PRP) with this scaffold in bone regeneration. Fifteen male white New Zealand rabbits were randomly divided into six groups, each involving 5 limbs. Full thickness bicortical defects were created in the proximal tibia of both pelvic limbs of rabbits. The defect was left untreated in the negative control group. In experimental groups the defect was filled with PRP (group 1), cellular fish scale (group 2), combination of cellular fish scale and PRP (group 3), acellular fish scale (group 4), and a combination of acellular fish scale and PRP (group 5). Fresh fish scales were decellularized to increase biocompatibility and reduce immunity reactions. Decellularization was confirmed by DAPI (4',6-diamidino-2-phenylindole) staining. The microstructure and surface characteristics of fish scales were assessed by scanning electron microscopy (SEM). Histopathological evaluation of bone healing was performed on day 56. Although there was no significant difference in the bone union among experimental groups, the union was superior in all experimental groups compared to control. Spongiosa and cortex formation were superior in the acellular groups. Furthermore, PRP promoted bone marrow formation. We concluded that fish scale is a biocompatible scaffold with a high regenerative potential.

Chronic Zoon vulvitis was successfully treated with platelet-rich plasma achieving a considerable reduction of the clinical symptoms and signs of an evident lesion.