Histological effect of platelet-rich plasma on temporomandibular joint osteoarthritis: systematic review in animal models

SUMMARY: The aim of this systematic review was to assess the histological effects of platelet-rich plasma (PRP) on temporomandibular joint osteoarthritis (TMJ-OA) in animal models. A systematic search was performed using PubMed, WoS, EMBASE, Science Direct and SCOPUS databases. The inclusion criteria were experimental studies in animal models that evaluated the use of PRP as a treatment for TMJ-OA with or without arthrocentesis/arthroscopy. Comparison was made to a healthy control group or to other treatment. The variables evaluated were the histological effects of the treatments, characteristics of the primary articles, characteristics of the sample studied and the risk of bias. The systematic search identified 120 studies. Eventually 5 studies were included in the analysis. Four of the studies showed a statistically significant repair in joint tissues and improvement of cartilage thickness in animals treated with PRP. The global risk of bias was unclear. The results of this systematic review suggest that PRP treatment in TMJ-OA has benefits at the histological level in cartilage, articular disc and articular bone tissue in animal models. However, due to the low number of studies and the risk of bias, further research is needed to recommend its use.

El objetivo de esta revisión sistemática fue evaluar los efectos histológicos del plasma rico en plaquetas (PRP) en la osteoartritis de la articulación temporomandibular (ATM-OA) en modelos animales. Se realizó una búsqueda sistemática en las bases de datos PubMed, WoS, EMBASE, Science Direct y SCOPUS. Los criterios de inclusión fueron estudios experimentales en modelos animales que evaluaran el uso de PRP como tratamiento para la ATM-OA con o sin artrocentesis/ artroscopia. La comparación se realizó con un grupo de control sano o con otro tratamiento. Las variables evaluadas fueron los efectos histológicos de los tratamientos, las características de los artículos primarios, las características de la muestra estudiada y el riesgo de sesgo. La búsqueda sistemática identificó 120 estudios. Finalmente se incluyeron 5 estudios en el análisis. Cuatro de los estudios mostraron una reparación estadísticamente significativa en los tejidos articulares y una mejora del grosor del cartílago en los animales tratados con PRP. El riesgo global de sesgo fue incierto. Los resultados de esta revisión sistemática sugieren que el tratamiento con PRP en la ATM-OA tiene beneficios a nivel histológico en el cartílago, el disco articular y el tejido óseo articular en modelos animales. Sin embargo, debido al escaso número de estudios y al riesgo de sesgo, se necesitan investigaciones adicionales para recomendar su uso.

Plasma rico en plaqueta en el tratamiento de la enfermedad degenerativa discal / Platelet-rich plasma in the treatment of degenerative disc disease

Introducción: La enfermedad degenerativa discal es una entidad frecuente y uno de los principales motivos de consulta. Genera altas tasas de discapacidad, años útiles perdidos, así como altos costos económicos por asistencia médica y grandes pérdidas monetarias. Su tratamiento es generalmente conservador, aunque en la actualidad se incluyen terapias biológicas novedosas. Objetivo: Describir las principales propiedades biológicas que hacen del plasma rico en plaquetas una terapéutica efectiva para la enfermedad degenerativa discal. Métodos: Se realizó una revisión no sistemática de la bibliografía basada en artículos que se publicaron en bases de datos indexadas en Infomed como Hinari, Ebsco, Scielo, Pubmed, Cubmed, Cocrhane, Scopus, LILACS; en idioma español, inglés y portugués, durante los últimos diez años. Desarrollo: Se expusieron características clínico epidemiológicas de la enfermedad degenerativa discal, así como las propiedades biológicas que le permiten al plasma rico en plaqueta tener una función activa en la regeneración del disco intervertebral o el retraso de la cascada de degradación de este. Se resaltan los principales estudios de acuerdo a la vía de administración del plasma rico en plaquetas y sus resultados. Conclusiones: De acuerdo con lo publicado por los autores, el plasma rico en plaquetas es una alternativa efectiva en el tratamiento de la enfermedad degenerativa discal por la producción de factores derivados de las plaquetas, que intervienen en la degeneración del disco intervertebral, siendo la vía intradiscal la que más se emplea(AU)

Introduction: Degenerative disc disease is a frequent condition and one of the main reasons to attend the consultation. It generates high rates of disability, useful years lost, as well as high economic costs for medical assistance and large monetary losses. Its treatment is generally conservative, although novel biological therapies are currently included. Objective: To describe the main biological properties that make platelet-rich plasma an effective therapy against degenerative disc disease. Methods: A nonsystematic review of the bibliography was carried out based on articles published, during the last ten years, in databases indexed in Infomed, such as Hinari, Ebsco, Scielo, Pubmed, Cubmed, Cocrhane, Scopus, and LILACS, in Spanish, English and Portuguese. Development: Clinical-epidemiological characteristics of degenerative disc disease were presented, as well as the biological properties that allow platelet-rich plasma to have an active function in the regeneration of the intervertebral disc or the delay of its degradation cascade. The main studies are highlighted, according to the route of administration of platelet-rich plasma and their results. Conclusions: According to what has been published by authors, platelet-rich plasma is an effective alternative in the treatment of degenerative disc disease, due to the production of factors derived from platelets, which intervene in the degeneration of the intervertebral disc, being the intradiscal pathway the most used(AU)

Resultados de los concentrados plaquetarios en la regeneración ósea guiada / Results of platelet concentrates in guided bone regeneration

Los defectos óseos alrededor de los implantes dentales son considerados enfermedades que afectan el soporte y estabilidad del implante dental lo que limita la oseointegración. El tratamiento de estos defectos involucra procedimientos de regeneración ósea guiada que se define como la reproducción o reconstitución de una parte perdida o dañada del tejido óseo periimplantario con el fin de restaurar su arquitectura y función. El plasma rico en plaquetas y el plasma rico en fibrina son concentrados de plaquetas autólogos ampliamente usados en la regeneración periodontal y regeneración ósea guiada; sin embargo, sus resultados clínicos, histológicos y radiográficos son discutidos cuando se tratan defectos óseos alrededor de implantes dentales. En la presente revisión se realizó una búsqueda de la información mediante las bases de datos de diferentes buscadores (PubMed, SciELO, Redalyc y ScienceDirect) para encontrar artículos que traten sobre el uso de los concentrados plaquetarios (plasma rico en plaquetas y plasma rico en fibrina) en la terapia de la regeneración ósea guiada. Clínicamente, los concentrados plaquetarios otorgan resultados favorables en la reducción de la profundidad de sondaje y ganancia de nivel de inserción clínica en el tratamiento de defectos infraóseos periodontales. Histológicamente, los concentrados plaquetarios favorecen la neoformación ósea aumentando la velocidad de regeneración. Radiográficamente, los concentrados plaquetarios favorecen el aumento de densidad ósea, relleno óseo y tejido mineralizado. Con ello, se logra una reducción significativa del tamaño del defecto óseo(AU)

Bone defects around dental implants are considered to be diseases affecting the support and stability of the implant, thus limiting osseointegration. Treatment of these defects involves guided bone regeneration procedures, defined as the reproduction or reconstitution of a part lost or damaged of the peri-implant bone tissue with the purpose of restoring its architecture and function. Platelet-rich plasma and fibrin-rich plasma are autologous platelet concentrates widely used in guided bone regeneration and periodontal regeneration. However, their clinical, histological and radiographic results are debated when bone defects around dental implants are dealt with. The present review included a search for information in the databases of various search engines (PubMed, SciELO, Redalyc and ScienceDirect) to find papers about the use of platelet concentrates (platelet-rich plasma and fibrin-rich plasma) in guided bone regeneration therapy. Clinically, platelet concentrates yield favorable results in reducing probing depth and raising the level of clinical insertion in the treatment of periodontal intraosseous defects. Histologically, platelet concentrates enhance bone neoformation, speeding up regeneration. Radiographically, platelet concentrates lead to an increase in bone density, bone filler and mineralized tissue. A significant reduction is thus achieved in the size of the bone defect(AU)

Cost and effectiveness of Platelet Rich Plasma in the healing of varicose ulcer: Meta-analysis / Costo y efectividad del Plasma Rico en Plaquetas en la cicatrización de úlcera varicosa: Metaanálisis / Custo e efetividade do Plasma Rico em Plaquetas na cicatrização de úlcera varicosa: Metanálise

ABSTRACT Objectives: to analyze the evidence on the cost and effectiveness of Plaque Rich Plasma in the treatment of venous ulcers compared to other topical therapies. Methods: systematic review, with search in the databases: COCHRANE, EMBASE, MEDLINE via PubMed, LILACS, CINAHL, SCOPUS, without temporal cut and in the English, Portuguese and Spanish languages. Results: fifteen articles were included, a cost-minimization analysis showed that the cost of Plaque Rich Plasma is € 163.00 ± 65.90, slightly higher than the cost of standard dressing. Regarding effectiveness, the results of the studies associated with the meta-analysis suggest a tendency that Plaque Rich Plasma is effective in the healing of venous ulcers. Conclusions: it is concluded that there are few studies about the cost of Platelet Rich Plasma and this product tends to be effective in the healing of venous ulcers. However, more controlled and randomized clinical studies are necessary in order to establish a stronger recommendation.

RESUMEN Objetivos: analizar las evidencias acerca del costo y de la efectividad del Plasma Rico en Plaquetas en el tratamiento de úlceras venosas comparado a las otras terapias tópicas. Métodos: revisión sistemática con la búsqueda en bases de datos: Cochrane Library, EMBASE, MEDLINE vía PubMed, LILACS, CINAHL, SCOPUS, hay un tiempo y en inglés, portugués y español. Resultados: se incluyeron 15 artículos, un análisis de costo-minimización demostró que el costo del Plasma Rico en Plaquetas es de € 163,00 ± 65,90, poco superior al costo del vendaje estándar. En cuanto a la efectividad, los resultados de los estudios asociados al metaanálisis sugieren una tendencia de que el Plasma Rico en Plaquetas es efectivo en la cicatrización de las úlceras venosas. Conclusiones: se concluye que hay pocos estudios acerca del costo del Plasma Rico en Plaquetas y que ese tiende a ser efectivo en la cicatrización de úlceras venosas. Todavía, son necesarios más estudios clínicos controlados y aleatorizados para que se pueda establecer una recomendación más fuerte.

RESUMO Objetivos: analisar as evidências acerca do custo e da efetividade do Plasma Rico em Plaquetas no tratamento de úlceras venosas comparado às outras terapias tópicas. Métodos: revisão sistemática, com busca nas bases de dados COCHRANE, EMBASE, MEDLINE via PubMed, LILACS, CINAHL, SCOPUS, sem recorte temporal e nos idiomas inglês, português e espanhol. Resultados: foram incluídos 15 artigos. Uma análise de custo-minimização demonstrou que o custo do Plasma Rico em Plaquetas é de €163,00 ± 65,90, pouco superior ao custo do curativo padrão. Quanto à efetividade, os resultados dos estudos associados à metanálise sugerem uma tendência de que o Plasma Rico em Plaquetas é efetivo na cicatrização das úlceras venosas. Conclusões: conclui-se que há poucos estudos acerca do custo do Plasma Rico em Plaquetas e esse produto tende a ser efetivo na cicatrização de úlceras venosas. Entretanto, são necessários mais estudos clínicos controlados e randomizados para que se possa estabelecer uma recomendação mais forte.

Evaluation of the effect of platelet-rich plasma on alveolar wound healing in rats / Evaluación del efecto del plasma rico en plaquetas en la cicatrización de heridas alveolares en ratas

Opinions about the clinical utility of platelet-rich plasma (PRP) vary, as a large number of experimental studies have questioned its efficacy. The purpose of this study was to evaluate the effects of PRP on experimental alveolar wound healing in rats. Fifty young adult male Wistar rats were divided in control and PRP groups and submitted to extraction of the right maxillary incisor. In the PRP group, blood was collected by cardiac puncture, and the socket was filled with a PRP gel. Animals were euthanized after 1, 3, 7, 14 and 30 days. Histological and histomorphometric analyses were performed at each experimental time point. Semiquantitative histological analysis showed that the PRP group exhibited significantly more collagen-matrix deposition and less bone-matrix formation in the socket than did the control group from 7 to 30 days. Histomorphometric analyses showed that the PRP group also exhibited lower bone-tissue areas than the control group at 7 (p=0.0250) and 14 days (p<0.0001), but at 30 days, no significant difference between the groups was observed. In the present study, PRP did not enhance alveolar wound healing, and PRP-treated rats exhibited low rates of bone deposition during the intermediate phases of alveolar socket repair.

Las opiniones sobre la utilidad clínica del plasma rico en plaquetas (PRP) varían, ya que un gran número de estudios experimentales han cuestionado su eficacia. El propósito de este estudio fue evaluar los efectos del PRP sobre la cicatrización experimental de heridas alveolares en ratas. Cincuenta ratas Wistar adultas fueron divididas en grupos control y PRP, y fueron sometidas a extracción del incisivo maxilar derecho. En el grupo de PRP, la sangre se recogió por punción cardiaca, y el alvéolo se llenó con un gel de PRP. Los animales se sacrificaron después de 1, 3, 7, 14 y 30 días. Se realizaron análisis histológicos e histomorfométricos en cada momento experimental. El análisis histológico semicuantitativo mostró que el grupo de PRP exhibió significativamente más deposición de matriz de colágeno y menos formación de matriz ósea en el receptáculo que el grupo control de 7 a 30 días. Los análisis histomorfométricos mostraron que el grupo PRP también exhibió áreas de tejido óseo inferiores al grupo control a 7 (p = 0,0250) y 14 días (p <0,0001), pero a los 30 días no se observó diferencia significativa entre los grupos. En el presente estudio, el PRP no mejoró la cicatrización de las heridas alveolares, y las ratas tratadas con PRP mostraron bajas tasas de deposición ósea durante las fases intermedias de la reparación de los receptáculos alveolares.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin

OBJECTIVES: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS: Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Role of the autologous mesenchymal stem cells compared with platelet rich plasma on cicatrization of cutaneous wounds in diabetic mice / Papel das células-tronco mesenquimais autólogas em comparação com plasma rico em plaquetas na cicatrização de feridas cutâneas em camundongos diabéticos

Chronic cutaneous lesions affect 15% of diabetic human patients and represent a risk 15 to 46 times larger of limb amputations compared to people with normal glycemia. It is assumed that half of these amputations could be prevented by early treatment of wounds, for example, with proper cell therapy. Objectives: In this study, the action of the autologous transplant of mesenchymal stem-cells (MSC) was evaluated compared to the treatment with autologous platelet rich plasma (PRP) in the cicatrization of cutaneous lesions induced in diabetic mice. These animals were previously treated with streptozootocin to induce diabetes mellitus and round wounds of 1.5cm in diameter were created in the posterior region. Diameters of the wounds and healing time were evaluated during 30 days and the results were submitted to variance analysis and Tukey's test average. It was noticed that the animals treated with MSC presented a more accelerated cicatrization of the cutaneous lesion than the animals treated with PRP. However, the treatment with PRP presented better results than just the daily asepsis of the lesions with saline or covering them with semi-permeable bandage. Besides, the use of semi-permeable bandage kept the cutaneous lesions of diabetic mice did not interfere negatively with cicatrization, proved to be harmless to use, but kept the cutaneous lesions more hydrated than the ones exposed to the environment.(AU)

Lesões cutâneas crônicas afetam 15% dos pacientes diabéticos e humanos representam um risco 15 a 46 vezes maior de amputações de membros em comparação com as pessoas com a glicemia normal. Supõe-se que a metade destas amputações poderia ser evitada por meio do tratamento precoce das feridas cutâneas com, por exemplo, uma adequada terapia celular. Objetivos: Neste estudo, a ação do transplante autólogo de células estaminais mesenquimais (MSC) foi avaliada em comparação com o tratamento com plasma rico em plaquetas autólogo (PRP) na cicatrização de lesões cutâneas induzidas em camundongos diabéticos. Estes animais foram previamente tratados com estreptozotocina para induzir diabetes mellitus e feridas redondas de 1,5 cm de diâmetro foram criadas na região posterior. Os diâmetros dos ferimentos e tempo de cicatrização foram avaliados durante 30 dias e os resultados foram submetidos à análise de variância e média pelo teste de Tukey. Verificou-se que os animais tratados com MSC apresentam uma cicatrização mais acelerada da lesão cutânea que do que os animais tratados com PRP. No entanto, o tratamento com PRP apresentou melhores resultados do que apenas a assepsia das lesões diariamente com solução salina ou cobrindo-os com atadura semi-permeável. Além disso, a utilização de atadura semi-permeável mantidas as lesões cutâneas de camundongos diabéticos não interfere negativamente com a cicatrização, provou ser inofensiva para usar, mas manteve as lesões cutâneas hidratadas mais do que os expostos ao meio ambiente.(AU)

Plasma rico en plaquetas, un tratamiento innovador en reumatología / Platelet-rich plasma, an innovative treatment in rheumatology

Las plaquetas o trombocitos son fragmentos citoplasmáticos irregulares, pequeños derivados de los megacariocitos. Poseen un rol fundamental en la hemostasia y en la reparación de tejidos, esta última desarrollada mediante la liberación de factores de crecimiento contenidos en sus gránulos ante estímulos como la injuria tisular. El plasma rico en plaquetas (PRP) consiste en un concentrado de plaquetas obtenido mediante centrifugación de sangre del propio paciente. Se utilizó inicialmente como compactante y sellante de implantes óseos en cirugía maxilofacial y dental. Actualmente, se ha hecho más conocido como alternativa terapéutica en lesiones de deportistas de alto rendimiento. Los exitosos resultados han provocado la expansión de su uso en otras áreas como la dermatología, estética facial y más recientemente la reumatología. El uso de PRP en osteoartritis ha demostrado ser efectiva aliviando el dolor y mejorando la funcionalidad, sin embargo, la diversidad de protocolos utilizados ha dificultado la estandarización del tratamiento.

Platelets or thrombocytes are irregular, small cytoplasmic fragments derived from megakaryocytes. They have a fundamental role in hemostasis and tissue repair, the latter developed by the release of growth factors contained in their granules to stimuli such as tissue injury. Platelet-rich plasma (PRP) consists of a platelet concentrate obtained by centrifugation of the patient’s own blood. It was initially used as a compactor and sealant of bone implants in maxillofacial and dental surgery. It has now become better known as a therapeutic alternative in high-performance sports injuries. The successful results have led to the expansion of its use in other areas such as dermatology, facial aesthetics and more recently rheumatology. The use of PRP in osteoarthritis has been shown to be effective in relieving pain and improving functionality, however the diversity of protocols used has made difficult the standardization of treatment.

Expressão de metaloproteinases de matriz e PCNA em úlceras de córnea profundas, induzidas em coelhos, tratadas com plasma rico em plaquetas / Expression of matrix metalloproteinases and PCNA in deep corneal ulcers induced in rabbits, treated with platelet-rich plasma

O objetivo deste estudo foi avaliar a influência do plasma rico (PRP) e pobre (PPP) em plaquetas na proliferação celular e expressão de metaloproteinases de matriz (MMPs), durante a reparação de úlceras corneais profundas. Foram utilizadas 45 coelhas, distribuídas em 3 grupos (G) experimentais (n=15), designados como grupos PRP (GR), PPP (GP) e Controle (GC), de acordo com o tratamento. Todos os animais foram submetidos à indução cirúrgica unilateral de úlcera corneal. No GR e GP, o sangue autólogo foi centrifugado, utilizando-se protocolo padronizado, e foram confeccionados os colírios de PRP e PPP, e instilados cinco vezes ao dia. No GC, foi utilizado colírio lubrificante. Cada grupo foi subdividido (n=5), segundo o momento final de avaliação, sendo 4 (M4), 7 (M7) e 30 dias (M30). As córneas dos animais foram processadas para avaliação morfológica e imuno-histoquímica para PCNA, MMP1, MMP2, MMP9, MT1-MMP e TIMP1. No M4, os níveis de MMP2 foram maiores no GP e GR, sendo que, no M7, esse comportamento foi observado apenas no GP. No M30, no GR, verificou-se maior número de células epiteliais e marcação para MMP1 que o GP. No GR, a proliferação celular foi maior no M4 que nos demais momentos, e a marcação para MMP2 foi maior no M4 que no M30. O PRP estimula a proliferação celular na fase inicial (M4) do tratamento quando comparado aos demais momentos, diferentemente dos demais tratamentos. O uso de colírios de plasma rico e pobre em plaquetas influencia a expressão de metaloproteinases de matriz envolvidas no processo de reparação corneal.

The aim of this study was to evaluate the influence of platelet-rich (PRP) and poor (PPP) plasma in cell proliferation and matrix metalloproteinases (MMPs) expression during the repair of deep corneal ulcers. Forty-five female rabbits were distributed in 3 experimental groups (G) (n = 15), referred to as PRP (GR), PPP (GP) and Control (GC) groups, in accordance with the treatment. All animals underwent surgical induction of unilateral corneal ulcer. PRP and PPP eye drops were made by using centrifuged blood through standardized protocol, and instilled five times a day. In GC, lubricant eye drops were used. Each group was subdivided (n = 5) according to the final time point, 4 (M4), 7 (M7) and 30 days (M30). The animals' corneas were processed for morphological and immunohistochemical analysis for PCNA, MMP1, MMP2, MMP9, MT1-MMP and TIMP1. In M4, the levels of MMP2 were higher in GP and GR, and in M7, this behavior was only observed in the GP. In M30, more epithelial cells and MMP1 expression were found in GR than GP. In GR, cell proliferation was higher in M4 than at other time points and MMP2 expression was higher in M4 than M30. The PRP stimulates cell proliferation in the early phase (M4) of treatment when compared to other time points, different from other treatments. The use of eye drops of platelet-rich and poor plasma influences the expression of matrix metalloproteinases involved in the corneal repair process.

Quantificação de fatores de crescimento na pele de equinos tratada com plasma rico em plaquetas / Quantification of growth factors in horse skin treated with platelet-rich plasma

O plasma rico em plaquetas (PRP) é um produto derivado da centrifugação do sangue total, sendo rico em fatores bioativos, como os de crescimento. Apesar da ampla utilização em processos cicatriciais, há controvérsia sobre a eficácia da terapia na cicatrização cutânea. O objetivo desse estudo foi quantificar e comparar a concentração dos fatores TGF-β1 e PDGF-BB no PRP, plasma sanguíneo e pele, durante diferentes fases do processo de cicatrização da pele tratada ou não com PRP [...] Também foram obtidas amostras de sangue com EDTA em todos os tempos mencionados. A quantificação dos fatores de crescimento TGF-β1 e PDGF-BB na pele, PRP e plasma sanguíneo foi realizada pela técnica ELISA.Os dados foram analisados estatisticamente pelo teste t, correlação de Pearson e regressão, utilizando nível de significância de 5 por cento. Não houve diferença entre os grupos, nos valores dos dois fatores de crescimento mensurados na pele, nos diferentes tempos. Também não houve correlação entre a quantidade dos fatores de crescimento presentes na pele e no plasma. Por outro lado, correlação positiva foi observada entre PRP e pele no grupo tratado, para os fatores de crescimento TGF-β1 (r=0,31) e PDGF-BB (r=0,38), bem como entre ambos os fatores de crescimento presentes no PRP (r=0,81). Considerando as concentrações dos fatores de crescimento no T0, os maiores valores cutâneos (p<0,05) do TGF-β1, em ambos os grupos, ocorreram nos tempos T3 e T5. Valores mais elevados (p<0,05) do PDGF-BB ocorreram no T4 (GT) e T5 (GC). No plasma não houve alteração nas concentrações desses fatores em relação ao T0, o que sugere que o PRP não acarreta efeito sistêmico, quando os procedimentos adotados na presente pesquisa são utilizados. A administração local de PRP no volume estudado, 12 h após indução cirúrgica de ferida cutânea na região glútea de equinos não ocasiona maiores concentrações dos fatores de crescimento TGF-β1 e PDGF-BB no plasma sanguíneo e pele, durante o processo de cicatrização.

Platelet-rich plasma (PRP) is a product derived from total blood centrifugation, rich in bioactive factors, such as growth factors. Despite largely used in healing processes, there is a controversy whether the therapy is effective in promoting skin healing. The objective of this study was to quantify and compare the concentrations of the factors TGF-β1 and PDGF-BB in PRP, blood plasma and skin, at different phases of the healing process of skin treated or not with PRP. [...] Quantification of TGF-β1 and PDGF-BB growth factors on the skin, PRP, and blood plasma was carried out by the ELISA technique. Data were statistically analyzed by the t test, Pearson correlation and regression, at a significance level of 5 percent. No difference was found between the groups in the values of the two growth factors measured on the skin, at the different times. Also, no correlation was found between the amount of growth factors present in the skin and plasma. On the other hand, a positive correlation was observed between PRP and skin in the treated group, for the growth factors TGF-β1 (r=0.31) and PDGF-BB (r=0.38), as well as between both growth factors present in PRP (r=0.81). Considering the growth factor concentrations at T0, the highest skin values (p<0.05) of TGF-β1, in both groups, occurred at T3 and T5. Higher values (p<0.05) of PDGF-BB occurred at T4 (TG) and T5 (CG). No plasma changes occurred at the concentration of these factors in relation to T0, suggesting that PRP does not cause a systemic effect when the procedures adopted in this research are used. Local administration of PRP in the volume studied, 12 h after surgical induction of cutaneous wound gluteal equine does not cause higher concentrations of the growth factors TGF-β1 and PDGF-BB in the plasma and skin during the healing process.

Uso do plasma rico em plaquetas no reparo de úlceras de córnea profundas induzidas em coelhos. Avaliação clínica e histomorfométrica / Use of platelet-rich plasma in the treatment of deep corneal ulcers induced in rabbits. Clinical and histomorphometric evaluation

Avaliou-se e comparou-se, clinicamente, por meio de histopatologia e morfometria, o processo de reparação corneana de úlceras experimentais induzidas em coelhos, com o uso de plasma rico em plaquetas (PRP) sob a forma de colírio ou tampão. Foram utilizados 60 coelhos, constituindo-se quatro grupos experimentais de 15 animais cada, designados grupo plaqueta (GP), grupo tampão (GT), grupo controle (GC) e grupo controle amniótica (GA). Os grupos experimentais foram subdivididos em três subgrupos (M4, M7, M30), de acordo com o período final de avaliação, aos quatro, sete e 30 dias, respectivamente. Não houve diferenças entre os tratamentos utilizados quanto aos sinais relacionados à sensibilidade ocular, quemose e secreção ocular. Os grupos tratados com PRP, na forma de tampão ou colírio, apresentaram menor opacidade corneana do que os animais tratados apenas com membrana amniótica no momento final de avaliação. Quanto à presença da úlcera corneana, os grupos tratados com PRP apresentaram menor ulceração corneana em relação aos demais grupos. No exame histomorfométrico, verificou-se maior epitelização corneana na fase inicial da lesão no tratamento à base de colírio de plasma rico em plaquetas. O uso da membrana amniótica promoveu espessamento do epitélio e estroma corneano, com sinergismo dela quando associada ao plasma rico em plaquetas.

The repair process induced corneal ulcer in rabbits using platelet-rich plasma in the form of eyedrop or clot was clinically evaluated and compared. Sixty rabbits were divided into four groups of 15 animals, denominated platelet group (PG), clot group (CLG), control group (CG), and amniotic control group (AG). Experimental groups were then subdivided into three groups (M4, M7, M30), corresponding to the end of the evaluation period. There were no differences between treatments regarding ocular sensitivity, chemosis and ocular secretion. The groups treated with PRP either as eyedrop or a clot showed less opacity than the animals treated only with amniotic membrane at the moment of the final evaluation. The presence of corneal ulcers in the groups treated with PRP showed lower intensity than the other groups. Histomorphometric examination showed that corneal epithelization in the initial phase of the lesion was greater when using PRP. The use of amniotic membrane promoted corneal epithelial and stromal thickness, as well as synergism when associated to PRP.

Efectividad del plasma rico en plaquetas en la cicatrización de implantes dentales: una revisión sistemática / Effectiveness of platelet rich plasma in the healing of dental implants: a systematic review

El plasma rico en plaquetas es un producto de la centrifugación diferencial de la sangre, logrando una alta concentración de plaquetas (600.000 a 1.500.000 x mm3), que al combinarse con cloruro de calcio comienza su activación, produciendo regeneración celular. Se ocupa actualmente dentro de procedimientos estéticos y quirúrgicos. En implantes dentales posee una efectividad por sobre el 92 por ciento, además disminuye el tiempo para la rehabilitación, reduciendo la reabsorción ósea luego de la exodoncia. El objetivo del presente estudio fue evaluar el efecto del tratamiento con PRP en cirugías de implantes dentales. Se realizó una revisión sistemática cuya metodología consistió en revisar ensayos clínicos aleatorizados del tema. Se buscó en PUBMED, Lylacs, Blackwell y Ebsco, en la biblioteca Cochrane y en literatura gris mediante búsqueda manual. Se consideró los siguientes criterios de selección: mayores de 18 años, candidatos a tratamientos rehabilitadores con implantes dentales, sin alteraciones sistémicas de importancia. La estrategia se resume en los siguientes puntos: Identificación del problema, Identificación de términos de búsqueda, Búsqueda sistemática, Selección de artículos mediante utilización de guías de análisis crítico, Incorporación de la información al REVMAN, Análisis de sensibilidad de los artículos y Meta análisis. Se concluye que la mezcla del plasma rico en plaquetas puede inducir una reacción más fuerte de hueso alrededor del implante.

The platelet rich plasma is a differential centrifugation product of the blood, getting a high concentration of platelets (600.000 to 1.500.000 x mm3), which when combined with calcium chloride begins its activation, resulting in cell regeneration. It is currently in aesthetic and surgical procedures. Dental implant has effectiveness over 92 percent, and decreases the time for rehabilitation, reducing bone resorption after extraction. The objective of this study was to evaluate the effect of treatment with PRP in dental implant surgery. We conducted a systematic review whose methodology was to review randomized clinical trials of the subject. W searched PUBMED, Lylacs, Blackwell and Ebsco, the Cochrane Library and books. We considered the following selection's criteria: over 18 years, candidates for dental implant rehabilitation treatment, without significant systemic changes.The strategy is summarized in the following: Identify the problem, identification of search terms, systematic search, selection of articles by using critical thinking guides, Incorporation of information to REVMAN, Sensitivity analysis of the articles, analysis of bias and Meta analysis. W conclude that the mixture of platelet affluent plasma can induce a stronger reaction of bone around the implant.

Association of mesenchymal stem cells with platelet rich plasma on the repair of critical calvarial defects in mice / Associação de células-tronco mesenquimais com plasma rico em plaquetas na reparação de defeitos críticos em calvária de camundongos

PURPOSE: To evaluate the effects of mesenchymal stem cells (MSC) from eight mice C57BL/6 gfp+ bone marrows expanded in cultures associated with platelets rich plasma (PRP) deriving from another eight mice, in the repair of critical defects in calvarial bone produced in twenty-four adult isogenic mice C57BL/6. METHODS: The animals were submitted to a cranial defect of 6.0mm in diameter and divided into two equal experimental groups. Control group did not receive treatment and the treated group received a MSC pellet containing 1.0 x 10(7) cells/mL associated with 50.0µL of plasma gel containing 1.0 x 10(9) autologous platelets within the defect. RESULTS: In the treated group was observed process of angiogenesis and bone repair better than control group. CONCLUSION: Mesenchymal stem cells derived from bone marrow of C57BL/6 gfp+ mice associated with PRP gel applied in bone critical defects produced in calvarial contributes positively to the process of bone repair.

OBJETIVO: Avaliar os efeitos da associação das células-tronco mesenquimais (MSC) oriundas da medula óssea de oito camundongos jovens C57BL/6 gfp+ e expandidas em culturas, com Plasma Rico em Plaquetas (PRP) provenientes de outros oito camundongos, na reparação de defeitos críticos confeccionados em calvária de 24 camundongos adultos C57BL/6. MÉTODOS: Os animais foram submetidos a um defeito craniano de 6,0mm de diâmetro e separados em dois grupos experimentais iguais. O grupo controle não recebeu tratamento e no grupo tratado foi administrado, no interior do defeito, pellet de MSC contendo 1,0 x 10(7) células/mL associado com 50,0µL de plasma em gel autólogo contendo 1,0 x 10(9) plaquetas. RESULTADOS: No grupo tratado verificou-se processo de angiogênese e reparação óssea superior ao grupo controle. CONCLUSÃO: A associação das células-tronco mesenquimais (MSC) derivadas da medula óssea de camundongos C57BL/6 gfp+ com gel de PRP aplicadas em defeitos ósseos críticos confeccionadas em calvária de camundongos C57BL/6 jovens, contribuiu positivamente para o processo de reparação óssea.

Treatment of human periodontal infrabony defects with hydroxyapatite+ β tricalcium phosphate bone graft alone and in combination with platelet rich plasma: A randomized clinical trial.

Background: The present study was aimed at comparing the clinical effectiveness of two regenerative techniques - platelet rich plasma (PRP) + bone graft (HA + β TCP) versus bone graft (HA + β TCP) + normal saline in the treatment of periodontal intrabony defects. Materials and Methods: Ten patients diagnosed with chronic periodontitis were enrolled in a randomized split mouth clinical trial. Following phase I therapy the sites were randomly assigned to the test group - PRP + bone graft (HA + β TCP) and control group - saline + bone graft (HA + β TCP). Clinical parameters recorded at baseline and 6 months included plaque index, probing pocket depth, relative attachment levels, and relative gingival margin levels. Hard tissue evaluation was done using digital radiography to evaluate the image intensity and therefore the radioopacity of a desired region of interest in the intrabony defect. Pre- and postoperative comparisons were made between the treatment groups at 6 months. Results: Test group sites showed a significantly higher reduction in pocket depth compared to control group sites. Test group sites showed a significantly higher amount of radioopacity in the regions of interest, indicative of better graft remodeling, compared to control group sites. Conclusion: (HA + β TCP) bone graft appears to be a beneficial material in the treatment of human periodontal intrabony defects. When combined with platelet-rich plasma there is a significantly higher reduction in probing pocket depth, higher gain in attachment levels and higher amount of radio-density seen in the intrabony defects.

Comparison between the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia

OBJECTIVE: To perform a comparative analysis of the effects of platelet-rich plasma and centrifuged bone marrow aspirate on the induction of bone healing in rabbits. METHOD: Twenty adult, male New Zealand rabbits were randomly separated into two equal groups, and surgery was performed to create a bone defect (a cortical orifice 3.3 mm in diameter) in the proximal metaphysis of each rabbit's right tibia. In the first group, platelet-rich plasma was implanted in combination with β-tricalcium phosphate (platelet-rich plasma group), and in the second group, centrifuged bone marrow in combination with β-tricalcium phosphate (centrifuged bone marrow group) was implanted. After a period of four weeks, the animals were euthanized, and the tibias were evaluated using digital radiography, computed tomography, and histomorphometry. RESULTS: Seven samples from each group were evaluated. The radiographic evaluation confirmed the absence of fractures in the postoperative limb and identified whether bone consolidation had occurred. The tomographic evaluation revealed a greater amount of consolidation and the formation of a greater cortical bone thickness in the platelet-rich plasma group. The histomorphometry revealed a greater bone density in the platelet-rich plasma group compared with the centrifuged bone marrow group. CONCLUSION: After four weeks, the platelet-rich plasma promoted a greater amount of bone consolidation than the bone marrow aspirate concentrate.

Efecto del plasma rico en plaquetas en la resistencia de un injerto tendíneo, en túnel óseo en modelo en animal / Effect of platelet-rich plasma in relation to mechanical strength of intra-tunel integration of tendon graft in animals

Introduction: Bone-tendon interface is one of the places for early failure in the ligament reconstruction surgery. In that way, osteintegration should be favored. Growth factors have been proposed to enhance tendon healing and tissue regeneration. Objective: To assess the effect of Platelet-Rich Plasma (PRP) in relation to the mechanical strength of intra-tunel integration of flexor tendon in a rabbit model. Methods: Experimental and control trial in animal model. Nine skeletally mature, New Zeland rabbits were used for this study (18 knees) performing a proximal tibia bone tunnel in one knee in which a flexor tendon graft was introduced, applying a dose of PRP in the bone tunnel. The other knee was used as control. Rabbits were sacrificed in three groups of three at de 2nd, 4th and 8th week. Biomechanical evaluation was performed, recording the force to achieve graft failure. Data analysis was done using Mann Whitney test. Results: The resistance obtained in the PRP group vs control group at 2nd week was 7.4 N vs 6.6 N (p = 0.51), at 4th week was 16 N vs 13.5 N (p = 0.27) and at 8th week was 21N vs 13.2 N (p = 0.51). Conclusion: Administration of local PRP in bone tunnels does not significantly modify mechanical strength of the graft in bone tunnel compared with controls.

Introducción: La interface tendón-hueso es uno de los sitios de falla precoz de la reconstrucción ligamentosa. Se han buscado distintas formas de aumentar la osteointegración del injerto. Existen estudios demostrando algún grado de utilidad del plasma rico en plaquetas (PRP) en relación a la cicatrización y regeneración de tejidos. Objetivo: Evaluar el efecto del plasma rico en plaquetas en la resistencia de la cicatrización intraósea de tendón flexor en un modelo de reconstrucción ligamentosa en conejos. Material y Método: Estudio experimental, controlado, en modelo animal. Nueve conejos de raza albina New Zeland, esqueléticamente maduros. Se estudiaron 9 conejos (18 rodillas), realizando un túnel óseo tibial proximal en una rodilla, donde se introdujo injerto de tendón flexor, administrándose una dosis autóloga de PRP en el túnel óseo. La otra rodilla se utilizó como control, los conejos se sacrificaron en grupos de 3 a la 2ª, 4ª y 8ª semana. Realizamos evaluación biomecánica, registrándose la fuerza necesaria para conseguir la falla del injerto. El análisis de datos se realizó mediante Test de Mann Whitney. Resultados: La resistencia obtenida en el grupo con PRP vs grupo control a la 2da semana fue 7,4 N vs 6,6 N (p = 0,51), a la 4ta semana fue 16 N vs 13,5 N (p = 0,27) y a la 8va semana fue 21 N vs 13,2 N (p = 0,51). Conclusiones: La administración local de PRP en los túneles óseos, no modifica en forma significativa la resistencia del injerto en el túnel óseo comparado con grupo control. Nivel de evidencia: II (ensayo clínico controlado no aleatorio).

Effects of platelet-rich plasma on healing of alveolar socket: Split-mouth histological and histometric evaluation in Cebus apella monkeys.

Context: The prediction of implant treatment is directly influenced by the quality of the remaining bone after tooth extraction. Aims : The purpose of this experimental study was to, histologically and histometrically, evaluate the bone repair process in the central areas of extraction sockets filled with platelet-rich plasma. Materials and Methods: Four young adult male Cebus apella monkeys were used. The extraction of both right and left inferior second premolars was accomplished. After extraction, in one of the extraction sockets, coagulum was maintained while in the other it was removed; the alveolus was dried with gauze compress and filled up with platelet concentrate. For PRP production, Sonnleitner's protocol was followed. The specimens for histological and histometric assessment were obtained in 30, 90, 120 and 180 days intervals. Results: In 30 days new bone formation was intense in both experimental and control sockets and no significant differences were observed between the two groups. After 90 days of the extraction, while the control group showed signs of decrease in osteogenesis, in the experimental unit, the process of bone formation and fibroblast-like cell proliferation remained intense. After 120 days, the PRP treated socket was occupied by large trabeculae of bone. After 180 days, the control unit was occupied mostly with bone marrow. The experimental unit remained occupied with large amounts of bone tissue. Conclusions: It was possible to conclude that bone repair was enhanced by the use of platelet- rich plasma in alveolar sockets.

Gel de plaquetas: arcabouço 3D para cultura celular / Platelet gel: 3D scaffold for cell culture

INTRODUÇÃO: O reparo tissular é o objetivo final da cirurgia. A cultura celular requer arcabouço mecânico que dê suporte ao crescimento celular e difusão dos nutrientes. O uso do plasma rico em plaquetas (PRP) como um arcabouço 3D possui diversas vantagens: é material biológico, de fácil absorção pós-transplante, rico em fatores de crescimento, em especial PDGF- ββ e TGF-β que estimula síntese de matriz extracelular na cartilagem. OBJETIVO: Desenvolver arcabouço 3D à base de PRP. MATERIAIS E MÉTODOS: Duas formas foram idealizadas: Sphere e Carpet. Condições estéreis foram utilizadas. O gel de plaquetas permaneceu em cultura celular, observado diariamente em microscópio invertido. RESULTADOS: Ambos arcabouços obtiveram sucesso, com aspectos positivos e negativos. DISCUSSÃO: A forma Sphere não aderiu ao plástico. Observou-se retração do gel e investigação ao microscópio dificultada devido às áreas opacas no campo visual. A forma Carpet não aderiu ao plástico e apresentou-se translúcida. O tempo de estudo foi de 20 dias. CONCLUSÕES: A produção de um arcabouço 3D PRP foi um sucesso, e trata-se de uma alternativa que necessita ser mais utilizado e investigado para que se consolide em uma rota eficiente e confiável na tecnologia de engenharia tissular, particularmente em cultura de tecido cartilaginoso.

INTRODUCTION: Tissue repair has been the ultimate goal of surgery. Cell culture requires a mechanical scaffold that supports cell growth and nutrient diffusion. Using platelet-rich plasma (PRP) as a 3D scaffold presents various advantages: it is a biological material, easily absorbed after transplantation, rich in growth factors, in particular, PDGF-ββ and TGF-β that stimulate extracellular matrix synthesis in cartilage culture. OBJECTIVE: To develop a PRP 3D scaffold. Material and METHODS: Two forms were idealized: Sphere and Carpet. Sterile conditions were used. The platelet gel remained in culture conditions, observed at an inverted microscope on a daily basis. RESULTS: Both forms were successful because they produced a 3D environment that supports cell growth, with positive and negative features. DISCUSSION: The Sphere form didn't attach to the plate. Gel retraction was observed and the investigation at the microscope was difficult, because of the opaque areas in the optical field. The Carpet form didn't retract, and didn't produce opaque areas. Follow-up time was 20 days. CONCLUSIONS: The production of a PRP 3D scaffold was successful, and this is an alternative requiring further investigation in order to establish an efficient and reliable route in tissue engineering technology, particularly in cartilage tissue culture.