Treatment of Chondral Knee Lesions with Autologous Chondrocytes Embedded in a Fibrin Scaffold. Clinical and Functional Assessment / Tratamento de lesões condrais no joelho com condrócitos autólogos embebidos em arcabouço de fibrina. Avaliação clínica e funcional

Abstract Objective The aim of our study is to analyze the clinical and functional results obtained using autologous chondrocytes embedded in a fibrin scaffold in knee joint injuries. Methods We included 56 patients, 36 men and 20 women, with a mean age 36 years. Six of the patients were professional athletes, with single knee injuries that were either chondral or osteochondral (43 chondral, 9 osteochondral, 2 cases of osteochondritis dissecans and 2 osteochondral fractures), 2 to 10 cm2 in size and ≤ 10 mm deep, with no signs of osteoarthritis. The location of the injury was in the patella (8), the medial femoral condyle (40) and lateral femoral condyle (7) and one in the trochlea. The mean follow-up was 3 (range: 1-6) years. The clinical course was assessed using the Cincinnati and Knee Injury and Osteoarthritis Outcome (KOOS) scores, 6 and 12 months after surgery. The paired Student t-test was used to compare pre-and postoperative results. Results Six months after the implant, patients resumed their everyday activities. On the assessment scores, their condition was improving in comparison with their presurgical state (p < 0.05). They were also able to carry out their sporting activities more easily than prior to surgery (p < 0.05). Conclusion The seeding of chondrocytes in fibrin may provide a favorable microenvironment for the synthesis of extracellular matrix and improved the clinical condition and activity of the patients 1 year after surgery.

Resumo Objetivo O objetivo do nosso estudo é analisar os resultados clínicos e funcionais do tratamento de lesões nas articulações do joelho com condrócitos autólogos embebidos em arcabouço de fibrina. Métodos O estudo foi realizado com 56 pacientes (36 homens e 20 mulheres) com idade média de 36 anos; 6 indivíduos eram atletas profissionais. Os pacientes apresentavam lesões únicas, condrais ou osteocondrais (43 condrais, nove osteocondrais, 2 casos de osteocondrite dissecante e duas fraturas osteocondrais) no joelho, com 2 a 10 cm2 de tamanho e ≤ 10 mm de profundidade, sem sinais de osteoartrite. As lesões estavam localizadas na patela (8), no côndilo femoral medial (40), no côndilo femoral lateral (7) e na tróclea (1). O período médio de acompanhamento foi de 3 anos (faixa de 1-6 anos). A evolução clínica foi avaliada pelos escores de Cincinnati e Knee Injury and Osteoarthritis Outcome (KOOS), 6 e 12 meses após a cirurgia. O teste t de Student pareado foi utilizado para comparação dos achados pré e pós-operatórios. Resultados Os pacientes retomaram suas atividades diárias 6 meses após o implante. Os escores avaliados demonstraram a melhora em comparação ao estado pré-cirúrgico (p < 0,05). Além disso, os pacientes conseguiram realizar suas atividades esportivas com mais facilidade do que antes da cirurgia (p < 0,05). Conclusão A cultura de condrócitos em fibrina pode proporcionar um microambiente favorável para a síntese de matriz extracelular e melhorar a condição clínica e a atividade dos pacientes 1 ano após a cirurgia

Recurrent pterygium resection associated to fibrin membrane graft: report of two cases / Resseção do pterígio recorrente associada ao enxerto de membrana fibrina: relato de dois casos

ABSTRACT We propose a novel surgical technique in cases of aggressive recurrent pterygium non-subsidiary of treatment with conjunctival autografts or antimetabolites. Two presented cases were treated with surgical excision and a sutured plasma rich in growth factors membrane (mPRGF) followed by rich in growth factors (PRGF) eye drops treatment. After surgery, dexamethasone, tobramycin and PRGF eye drops were prescribed for 6 weeks. After a 12-month and 3-year post-surgical follow-up respectively, treated eyes with mPRGF did not present relapse, and visual acuity improved in both cases. No ocular complications, pain, eye discomfort nor other symptoms were observed. The combined use of PRGF eye drops and mPRGF seems an effective and safe therapy for recurrent pterygium.

RESUMO Nós propomos uma nova técnica cirúrgica em casos de pterígio agressivo recorrente não subsidiário de tratamento com autoenxertos conjuntivais ou antimetabólitos. Dois casos foram tratados com excisão cirúrgica e um plasma suturado rico em membrana de fatores de crescimento (mPRGF), seguido de tratamento com colírios ricos em fatores de crescimento (PRGF). Após a cirurgia, foram prescritos colírios de dexametasona, tobramicina e PRGF por 6 semanas. Após 12 meses e 3 anos de acompanhamento pós-cirúrgico respectivamente, os olhos tratados com mPRGF não apresentaram recidiva e a acuidade visual melhorou nos dois casos. Não foram observadas complicações oculares, dor, desconforto ocular ou outros sintomas. O uso combinado de colírios de PRGF e mPRGF parece uma terapia eficaz e segura para o pterígio recorrente.

Factores de crecimiento en el plasma: herramienta terapéutica en dermatología / Growth factors in plasma: therapeutic tool in dermatology

Las plaquetas contienen una gran cantidad de factores de crecimiento que participan en los procesos de cicatrización tisular. Entre ellos, el factor de crecimiento derivado de las plaquetas (PDGF), el factor de crecimiento transformante (TGF), el factor plaquetario 4 (PF4), la interleucina (IL)-1, el factor angiogénico derivado de las plaquetas (PDAF), el factor de crecimiento endotelial (VEGF), el factor de crecimiento epidérmico (EGF), el factor de crecimiento endotelial derivado de las plaquetas (PDEGF), el factor de crecimiento de células epiteliales (ECGF) y el factor de crecimiento similar a la insulina (IGF). El plasma rico en plaquetas (PRP) es un derivado sanguíneo concentrado de la sangre total con una alta concentración de plaquetas. Otro componente esencial del PRP son las proteínas que actúan a nivel de la adhesión celular (fibrina, fibronectina y vitronectina), que proporcionan el soporte estructural necesario para la migración celular y para la proliferación y crecimiento tridimensional de los tejidos sobre los que actúa. La fibrina es la forma activada del fibrinógeno, sustrato final de todas las reacciones de coagulación, se transforma en fibrina insoluble por acción de la trombina. El gel de fibrina polimerizado constituye la primera matriz cicatricial de las heridas. Tanto el plasma rico en plaquetas como las mallas de fibrina varían en la composición y concentración de factores de crecimiento, proteínas y citocinas. En este trabajo se revisan las características de estos productos biológicos, su aplicación en dermatología así como los principales requisitos para su preparación(AU)

Platelets contain a large amount of growth factors involved in the processes of tissue healing. Among them, plateletderived growth factor (PDGF), transforming growth factor (TGF), platelet factor 4 (PF4), interleukin (IL) -1, angiogenic factor derived from platelets (PDAF) , the endothelial growth factor (VEGF), the epidermal growth factor (EGF), the plateletderived endothelial growth factor (PDEGF), the epithelial cell growth factor (ECGF) and the Insulin like growth factor (IGF). Platelet-rich plasma (PRP) is a concentrated whole blood derivate with a high concentration of platelets. Another essential component of PRP are proteins acting on cell adhesion (fibrin, fibronectin and vitronectin), which provide the structural support necessary for cell migration and proliferation as well as three-dimensional growth of the tissues on which they act. Fibrin is the activated form of fibrinogen, the final substrate of all coagulation reactions. It is transformed into insoluble fibrin by the action of thrombin. The polymerized fibrin gel constitutes the first cicatricial matrix of wounds. Both plateletrich plasma and fibrin meshes vary in the composition and concentration of growth factors, proteins and cytokines. In this work we review the characteristics of these biological products, their application in dermatology as well as main requirements for their preparation(AU)

Avaliação da qualidade dos agregados leucoplaquetários / Evaluation of the quality of the leuco platelet aggregates

Objetivo ­ Avaliar a qualidade do plasma rico em plaquetas (PRP) e da fibrina rica em plaquetas (PRF) obtidos através de alguns tipos de protocolos de obtenção por meio da contagem de plaquetas e leucócitos nos materiais. Métodos ­ Foram coletadas amostras de sangue de voluntários mediante aprovação do Comitê de Ética em Pesquisa (CEP). As amostras foram centrifugadas em diferentes rotações e tempos (1300 RPM por 5 minutos, 550 RPM por 5 minutos e 550 RPM por 3 minutos). As concentrações de plaquetas e leucócitos foram avaliadas no Coulter LH 750 analyzer. Os resultados foram submetidos a análise estatística (Graph Pad Prism). Resultados ­ As dosagens de plaquetas foram significativamente maiores (p<0.0001) no protocolo de PRF centrifugado a 1300 rpm em comparação com os outros materiais, e as dosagens de leucócitos foram maiores no PRF centrifugado a 550 rpm (p<0.05). Conclusão ­ Os resultados desse trabalho sugerem que a velocidade de centrifugação, o uso de anticoagulante e o tempo de centrifugação são alguns interferentes que afetam a qualidade do material obtido impactando na diminuição do número de células presentes no material. Os resultados também apontam que o PRF apresenta maiores concentrações celulares, principalmente próximo à camada de leucócitos

Objective ­ To evaluate the quality of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) obtained through some types of protocols for obtaining platelet and leukocyte counts in the materials. Methods ­ Blood samples were collected from volunteers with the approval of the Research Ethics Committee (CEP). The samples were centrifuged at different speeds and times (1300 RPM for 5 minutes, 550 RPM for 5 minutes and 550 RPM for 3 minutes). Platelet and leukocyte concentrations were evaluated on the Coulter LH 750 analyzer. The results were subjected to statistical analysis (Graph Pad Prism). Results ­ Platelet dosages were significantly higher (p <0.0001) in the PRF protocol centrifuged at 1300 rpm compared to other materials, and leukocyte dosages were higher in PRF centrifuged at 550 rpm (p <0.05). Conclusion ­ The results of this work suggest that the centrifugation speed, the use of anticoagulant and the centrifugation time are some interferents that affect the quality of the material obtained impacting on the decrease of the number of cells present in the material. The results also point out that PRF presents higher cellular concentrations, mainly near the leukocyte layer

Uso do plasma rico em plaquetas (PRP) e plasma rico em fibrina (PRF) em defeitos peri-implantares: análises biomecânica e histomorfométrica / The use of platelet rich plasma (PRP) and fibrin rich plasma (PRF) in peri-implant defects: biomechanical and histomorphometric analyzes

O presente trabalho teve o objetivo avaliar o uso do plasma rico em plaquetas (PRP) e plasma rico em fibrina (PRF) em defeitos peri-implantares por meio das análises biomecânica e histomorfométrica. Para tanto, 36 ratos machos adultos foram divididos em 3 grupos: controle (CO), plasma rico em plaquetas (PRP) e plasma rico em fibrina (PRF). Previamente à realização dos procedimentos cirúrgicos, foram coletados 3 ml de sangue de cada animal via punção cardíaca, seguindo-se pelos respectivos protocolos de centrifugação para obtenção de PRP e PRF. Um defeito ósseo foi preparado na tíbia esquerda e um implante foi instalado manualmente. Conforme o grupo experimental, o defeito peri-implantar não sofreu intervenção ou foi preenchido com PRP ou PRF. A eutanásia foi realizada em 20 e 40 dias. Os resultados mostraram que houve diferença estatística significativa presente intergrupos e interperíodos (p< 0,05) na análise biomecânica. Os resultados histológicos apresentaram maior atividade celular nos grupos experimentais em relação ao grupo controle. Os dados sobre a área óssea neoformada (AON) demonstraram uma maior formação óssea nos grupos PRP e PRF em relação ao grupo controle. Entretanto, entre todos os grupos não houve diferença estatística significativa, assim como na análise entre os grupos e os períodos. Contudo, entre os períodos houve diferença estatística significativa (p< 0,001). A aplicação de PRP nos defeitos peri-implantares em tíbias de ratos mostrou-se mais eficaz na resposta de estabilidade do implante e na neoformação óssea sendo superior ao plasma rico em fibrina (PRF) e ao grupo controle (coágulo). Relevância Clínica: os defeitos peri-implantares são uma realidade clínica e o uso de concentrados plaquetários é uma alternativa para um tratamento. A literatura apresenta resultados satisfatórios em relação às altas concentrações de fatores de crescimento que podem afetar o processo de regeneração tecidual e neoformação óssea(AU)

The aim of the present study was to evaluate the use of platelet-rich plasma (PRP) and platelet rich fibrin (PRF) in peri-implant defects submitted to biomechanical and histomorphometric analysis. Thirty-six adult male rats were divided into 3 groups: control (CO), platelet rich plasma (PRP) and fibrin rich plasma (PRF). Prior to the surgical procedures, 3 ml of blood were collected from each animal via cardiac puncture, followed by the respective centrifugation protocols to obtain PRP and PRF. A bone defect was prepared in the left tibia and an implant was manually installed. The defect was filled with PRP, PRF or own clot. Euthanasia was performed at 20 and 40 days. The results showed that there was statistically significant difference between groups and periods (p < 0.05) in the biomechanical analysis. The histological results showed higher cellular activity in the experimental groups compared to the control group. Data on the newly bone area showed a higher bone formation in the PRP and PRF groups compared to the control group. However, there was no statistically significant difference in all groups, as well as in the analysis between groups and periods. Only between the periods there was a statistically significant difference (p < 0.001). The application of PRP to peri-implant defects in rat tibias was more effective in implant stability response and bone neoformation being superior to fibrin-rich plasma (PRF) and control group (clot)(AU)

Chronic venous ulcers: a review on treatment with fibrin sealant and prognostic advances using proteomic strategies

Venous ulcers are the main causes of chronic lower-limb ulcers. The healing difficulties encourage the research and development of new products in order to achieve better therapeutic results. Fibrin sealant is one of these alternatives. Besides being a validated scaffold and drug delivery system, it possesses excellent healing properties. This review covered the last 25 years of the literature and showed that the fibrin sealant is used in various clinical situations to promote the healing of different types of ulcers, especially chronic ones. These are mostly venous in origin and usually does not respond to conventional treatment. Commercially, only the homologous fibrin sealants obtained from human blood are available, which are highly efficient but very expensive. The heterologous fibrin sealant is a non-commercial experimental low-cost product and easily produced due to the abundance of raw material. The phase I/II clinical trial is already completed and showed that the product is safe and promisingly efficacious for the treatment of chronic venous ulcers. In addition, clinical proteomic strategies to assess disease prognosis have been increasingly used. By analyzing liquid samples from the wounds through proteomic strategies, it is possible to predict before treatment which ulcers will evolve favorably and which ones will be difficult to heal. This prognosis is only possible by evaluating the expression of isolated proteins in exudates and analysis using label-free strategies for shotgun. Multicentric clinical trials will be required to evaluate the efficacy of fibrin sealant to treat chronic ulcers, as well as to validate the proteomic strategies to assess prognosis.(AU)

Neuroprotection and immunomodulation by dimethyl fumarate and a heterologous fibrin biopolymer after ventral root avulsion and reimplantation

Ventral root avulsion (VRA) is an experimental approach in which there is an abrupt separation of the motor roots from the surface of the spinal cord. As a result, most of the axotomized motoneurons degenerate by the second week after injury, and the significant loss of synapses and increased glial reaction triggers a chronic inflammatory state. Pharmacological treatment associated with root reimplantation is thought to overcome the degenerative effects of VRA. Therefore, treatment with dimethyl fumarate (DMF), a drug with neuroprotective and immunomodulatory effects, in combination with a heterologous fibrin sealant/biopolymer (FS), a biological glue, may improve the regenerative response. Methods: Adult female Lewis rats were subjected to VRA of L4-L6 roots followed by reimplantation and daily treatment with DMF for four weeks. Survival times were evaluated 1, 4 or 12 weeks after surgery. Neuronal survival assessed by Nissl staining, glial reactivity (anti-GFAP for astrocytes and anti-Iba-1 for microglia) and synapse preservation (anti-VGLUT1 for glutamatergic inputs and anti-GAD65 for GABAergic inputs) evaluated by immunofluorescence, gene expression (pro- and anti-inflammatory molecules) and motor function recovery were measured. Results: Treatment with DMF at a dose of 15 mg/kg was found to be neuroprotective and immunomodulatory because it preserved motoneurons and synapses and decreased astrogliosis and microglial reactions, as well as downregulated the expression of pro-inflammatory gene transcripts. Conclusion: The pharmacological benefit was further enhanced when associated with root reimplantation with FS, in which animals recovered at least 50% of motor function, showing the efficacy of employing multiple regenerative approaches following spinal cord root injury.(AU)

Uso de plasma rico en fibrina comparado con colágeno en el tratamiento de recesión gingival utilizando la técnica estenopéica. Ensayo clínico aleatorizado / Use of fibrin-rich plasma compared to collagen in the treatment of gingival recession using the stenopic technique. Randomized clinical trial

La recesión gingival (RG) es un problema de salud bucodental frecuente que aumenta con la edad, predispone a hipersensibilidad dentaria, caries radicular, inflamación gingival y efectos antiestéticos. El objetivo de este ensayo clínico aleatorizado fue evaluar comparativamente el efecto clínico del recubrimiento radicular utilizando la técnica estenopéica Pinhole con colágeno y la técnica estenopéica Pinhole modificada al incorporarle plasma rico en fibrina (PRF). Veintiséis participantes sistémicamente sanos, con diagnóstico de RG grado I de Miller, fueron reclutados y seguidos por 6 meses después de la cirugía. Los parámetros clínicos registrados fueron nivel de inserción clínica (NIC), RG y banda de encía queratinizada. Los participantes fueron asignados aleatoriamente a un grupo en quienes se utilizó PRF con 14 participantes, tratando 36 piezas dentales, y otro grupo en quienes se utilizó membrana de colágeno con 12 participantes, tratando 35 piezas dentales. Los resultados muestran un logro de ganancia en el NIC en ambos grupos, (M = 45.24 %, DE = 17.37 %) en el grupo PRF y (M = 47.37 %, DE = 15.67 %) en el grupo colágeno, diferencia que no fue significativa (p = .59). En ambos grupos existió un aumento significativo en la banda de encía queratinizada (p < .01). El uso de PRF como material de relleno al realizar la técnica estenopéica genera resultados similares al ser comparado con la técnica convencional que utiliza colágeno. Al presentar un menor costo el PRF aumenta las posibilidades que más personas tengan acceso al tratamiento.

Gingival recession (GR) is a frequent oral health disease that increases with age and may increase risk of dental hypersensitivity, root decay, gingival inflammation and aesthetic problems. The aim of this randomized clinical trial was to compare clinical parameters of dental root coverage using Pinhole technique with collagen and modi¬fied Pinhole technique using platelet-rich fibrin (PRF). Twenty-six participants, systemically healthy, with Miller class I GR diagnosis, were recruited and measured at baseline and after 6 months follow-up. Clinical parameters measured included clinical attachment level (ICL), GR and keratinized gingival width (KGW). All participants were randomly assigned to a group using PRF, with 14 participants and 36 teeth treated, and other group using collagen, with 12 participants and 35 teeth treated. Both PRF group and collagen group gained ICL, (M = 45.24 %, SD = 17.37 %) in PRF group and (M = 47.37 %, SD = 15.67 %) in collagen group, with no statistically significant difference (p = .59). Both groups gained KGW (p < .01). Use of PRF as filled material by using Pinhole technique resulted in similar clinical improvements compare to collagen as filled material. Considering that PRF is cheaper than collagen, it increases chances that people can have access to treatment.

Efectividad del plasma rico en fibrina y membrana de colágeno en la regeneración ósea guiada / Effectiveness of fibrin-rich plasma and collagen membrane in guided bone regeneration

RESUMEN: Objetivo: de este estudio fue determinar la efectividad de dos biomateriales, el plasma rico en fibrina (PRF) y la membrana de colágeno en la regeneración ósea guiada. Materiales y método: Fueron utilizados 30 cobayos adultos machos entre 900 a 1100 g. divididos en tres grupos de 10 cobayos cada uno (Grupo A: Control, grupo B: Membrana de colágeno y grupo C: Plasma rico en fibrina). A cada grupo se le creó un defecto óseo mandibular unilateral de 2mm. Al grupo A no se colocó un biomaterial, en los grupos B y C sí se colocaron los biomateriales en los defectos óseos. A los 15 y 30 días de cicatrización se realizaron cortes histológicos para evaluar la cantidad de fibroblastos, osteocitos y osteoblastos. Resultados: A los 15 días el grupo C formó 40,6 ± 8,08 osteocitos/camp y el grupo B 27,6 ± 4,72 (p<0.05); a los 30 días el grupo C: 30,6 ± 11,55 y el grupo B: 23,6 ±3,85 (p>0.05). Conclusión: El PRF induce una mayor proliferación celular de forma significativa que los otros grupos en los primeros días de cicatrización; a los 30 días la proliferación es similar con el grupo de membrana de colágeno sin existir diferencias significativas.

ABSTRACT: Aim: of this study was to determine the effectiveness of two biomaterials, fibrin-rich plasma (PRF) and collagen membrane in guided bone regeneration. Materials and method: Thirty male guinea pigs were used, weighing between 900 and 1100 g., divided into three groups of 10 guinea pigs each (Group A: control, group B: collagen membrane and group C: fibrin-rich plasma). Each group had a 2-mm unilateral mandibular bone defect. Group A did not receive any biomaterial; in groups B and C the biomaterials were used in the bone defects. After 15 and 30 days of healing, histological sections were performed to evaluate the amount of fibroblasts, osteocytes and osteoblasts. Results: After 15 days, group C formed 40.6 ± 8.08 osteocytes / camp and group B 27.6 ± 4.72 (p <0.05); After 30 days, group C: 30.6 ± 11.55 and group B: 23.6 ± 3.85 (p> 0.05). Conclusion: During the first 15 days of healing, PRF induces a greater cellular proliferation than the other groups in a significant way; after 30 days, the proliferation is similar to the collagen membrane group without significant differences.

Produção e purificação integrada de protease fibrinolítica de Mucor subtilissimus UCP 1262 / Integrated production and purification of fibrinolytic protease from Mucor subtilissimus UCP 1262

As enzimas fibrinolíticas podem ser obtidas de micro-organismos por meio de processos fermentativos. O presente trabalho teve como objetivo avaliar a produção e extração integrada da protease fibrinolítica de Mucor subtilissimus UCP 1262 usando sistema de duas fases aquosas (SDFA). O processo integrado foi realizado para avaliar a produção, partição e recuperação da protease fibrinolítica, segundo planejamento experimental 23, utilizando como variáveis independentes a massa molar do polietileno glicol (PEG), a concentração do PEG e a concentração do sulfato de sódio. A maior atividade fibrinolítica (15,40U/mL) foi obtida na fase rica em sulfato de sódio no ensaio composto por 10% de sal e 18% de PEG 8000 (g/mol). Recuperações superiores a 80% foram obtidas. A protease fibrinolítica apresentou pH ótimo 7,0, estabilidade entre os pH 6,0 e 8,5, temperatura ótima 50°C, sendo estável de 10°C a 50°C. A enzima foi classificada como uma serino protease, com massa molecular de 52kDa. Como resultado, o processo é notavelmente eficaz para pré-purificar a protease fibrinolítica com baixo custo e rapidez significativa. Quando comparada a outras técnicas de produção e purificação isoladas, a fermentação extrativa é um processo digno a ser substituto das etapas iniciais de separação convencionais.(AU)

Fibrinolytic enzymes can be obtained from microorganisms through fermentative processes. The study aimed to evaluate the fibrinolytic protease production and integrated extraction from Mucor subtilissimus UCP 1262 by extractive fermentation using Aqueous Two-Phase Systems (ATPS). The integrated process was carried out to assess the production, partition and fibrinolytic enzyme recovery, according to a 2 3 -experimental design, using as independent variables Polyethylene glycol (PEG) molar mass, PEG and sodium sulphate concentration, concentration. The highest fibrinolytic activity (15.40U/mL) was obtained in sodium sulfate rich phase in the assay comprising of 10% of salt and 18% of PEG 8000 (g/mol). Yield greater than 80% was obtained. The fibrinolytic protease presented optimum pH 7.0 and stability between pH 6.0 and 8.5, and optimum temperature 50°C, stable between 10°C to 50°C. The enzyme was classified as a serine-protease with 52kDa of molecular weight. As a result, the process is remarkably effective to pre-purify the fibrinolytic protease with a low cost and significantly faster processing time. When compared to other isolated production and purification techniques the extractive fermentation is worthy of being a candidate to replace the initial stages of conventional separation processes.(AU)

Fibrin biopolymer as scaffold candidate to treat bone defects in rats

Bone tissue repair remains a challenge in tissue engineering. Currently, new materials are being applied and often integrated with live cells and biological scaffolds. The fibrin biopolymer (FBP) proposed in this study has hemostatic, sealant, adhesive, scaffolding and drug-delivery properties. The regenerative potential of an association of FBP, biphasic calcium phosphate (BCP) and mesenchymal stem cells (MSCs) was evaluated in defects of rat femurs. Methods: Adult male Wistar rats were submitted to a 5-mm defect in the femur. This was filled with the following materials and/or associations: BPC; FBP and BCP; FBP and MSCs; and BCP, FBP and MSCs. Bone defect without filling was defined as the control group. Thirty and sixty days after the procedure, animals were euthanatized and subjected to computed tomography, scanning electron microscopy and qualitative and quantitative histological analysis. Results: It was shown that FBP is a suitable scaffold for bone defects due to the formation of a stable clot that facilitates the handling and optimizes the surgical procedures, allowing also cell adhesion and proliferation. The association between the materials was biocompatible. Progressive deposition of bone matrix was higher in the group treated with FBP and MSCs. Differentiation of mesenchymal stem cells into osteogenic lineage was not necessary to stimulate bone formation. Conclusions: FBP proved to be an excellent scaffold candidate for bone repair therapies due to application ease and biocompatibility with synthetic calcium-based materials. The satisfactory results obtained by the association of FBP with MSCs may provide a more effective and less costly new approach for bone tissue engineering.(AU)

Unique heterologous fibrin biopolymer with hemostatic, adhesive, sealant, scaffold and drug delivery properties: a systematic review

Fibrin biopolymers, previously referred as "fibrin glue" or "fibrin sealants", are natural biomaterials with diverse applications on health. They have hemostatic, adhesive, sealant, scaffold and drug delivery properties and have become widely used in medical and dental procedures. Historically, these biomaterials are produced from human fibrinogen and human or animal thrombin, and the possibility of transmission of infectious diseases by human blood is not ruled out. In the 1990s, to overcome this problem, a new heterologous biomaterial composed of a thrombin-like enzyme purified from Crotalus durissus terrificus venom and a cryoprecipitate rich in fibrinogen extracted from buffaloes Bubalus bubalis blood has been proposed. Therefore, a systematic review of studies on exclusively heterologous fibrin sealants published between 1989 and 2018 was carried out using the following databases: PubMed, SciELO and Google Scholar. The keyword used was "heterologous fibrin sealant". The search resulted in 35 scientific papers in PubMed, four in SciELO and 674 in Google Scholar. After applying the inclusion/exclusion criteria and complete reading of the articles, 30 studies were selected, which formed the basis of this systematic review. It has been observed that the only completely heterologous sealant is the one produced by CEVAP/UNESP. This heterologous biopolymer is proven effective by several studies published in refereed scientific journals. In addition, clinical trials phase I/II for the treatment of chronic venous ulcers authorized by the Brazilian Health Regulatory Agency (ANVISA) were completed. Preliminary results have indicated a safe and promising effective product. Phase III clinical trials will be proposed and required to validate these preliminary findings.(AU)

Niveles plaquetarios y marcadores de disfunción endotelial multiorgánica en síndrome HELLP / Platelet levels and multiorganic endothelial dysfunction markers in the Hellp Syndrome (Hemolysis, elevated liver enzimes, low platelets)

HELLP syndrome (hemolysis, elevated liver enzimes, low platelets count) is one of the major complications of the progression of thrombotic microangiopathies characterized by thrombocytopenia, hemolistic anemia and organic dysfunction. It can be found in between 0,5 - 0,9 % of all pregnancies, and between 4- 14 % in all those women who develop preeclampsia. The general objectives of this report were to describe the relationship existing between the platelet levls and the organic endothelial dysfunction because of the HELLP syndrome, and to determine the perinatal results, during the 10 yr. period of the study, in patients that were assited between 2007 and 2016.

Plasminogenemia asociada a conjuntivitis leñosa / Plasminogen Deficiency and Ligneous Conjunctivitis

El artículo presenta el caso clínico de un joven de 18 años de edad sin antecedente familiares de enfermedad crónica o hereditaria, nacido a término, sin complicaciones, quien desde los dos días de vida presentó una lesión tipo masa en la conjuntiva tarsal. Inicialmente, recibió tratamiento farmacológico tópico y seguimiento por oftalmología, por conjuntivitis bilateral persistente, masas tarsales recidivantes y cataratas en ambos ojos, por lo que requirió siete intervenciones con pobre respuesta al manejo farmacológico y quirúrgico. A los seis meses de vida se le diagnosticó hidrocefalia, que requirió manejo con derivación del ventrículo peritoneal. Dada la persistencia de la sintomatología y la refractariedad al tratamiento, se ampliaron los estudios y en una junta médica se sugirió el diagnóstico de conjuntivitis leñosa asociada a alteración del plasminógeno. Este diagnóstico fue confirmado por laboratorio clínico, que mostró sus bajas concentraciones de plasminógeno en muestras tomadas con intervalos de dos meses en tres ocasiones: 16,9%, 11,1%, 18,6% (valores de referencia: 70-150%). Se le indicó heparina de bajo peso molecular antes de procedimientos quirúrgicos mayores y triamcinolona tópica según síntomas oculares.

We present a case of an 18-year-old patient without a family history of ocular disease, born full term without complications, within his first 2 days a mass in the tarsal conjunctiva appeared. Initially he received topical treatment and follow-up by the ophthalmology department with a diagnosis of persistent bilateral conjunctivitis, relapsing tarsal masses and cataracts in both eyes requiring a total of 7 surgical interventions with a poor response. At the age of 6 months he was diagnosed with hydrocephalus and required a ventricular-peritoneal shunt. Giren the persistence of the symptoms, further studies were made and a medical board made the diagnosis of ligneous conjunctivitis associated to low levels of plasminogen. The diagnosis was confirmed by decreased levels of plasminogen in serum measured three times with 2 months intervals: 16.9%, 11.1%, 18.6% (reference valúes 70'150%). Low molecular weight heparin was ordered before surgical procedures, and topical triamcinolone applied according to ocular symptoms.

Comparison of arterial repair through the suture, suture with fibrin or cyanoacrylate adhesive in ex-vivo porcine aortic segment

Abstract Introduction: Tissue adhesives can be used as adjacent to sutures to drop or avoid bleeding in cardiovascular operations. Objective: To verify the efficiency of fibrin and cyanoacrylate adhesive to seal arterial sutures and if the adhesives penetrate through suture line to the inner of arteries. Methods: 20 abdominal aorta segments of pigs were divided into two groups according to the adhesive which would be used as adjacent to the suture. In every arterial segment an arteriotomy was done, followed by a conventional artery closure. Afterwards a colloidal fluid was injected inside the arterial segment with a simultaneous intravascular pressure monitoring up to a fluid leakage through the suture. This procedure was repeated after application of one of the adhesives on the suture in order to check if the bursting pressure increases. The inner aorta segments also were analyzed in order to check if there was intraluminal adhesive penetration. Results: In Suture 1 group, the mean arterial pressure sustained by the arterial suture reached 86±5.35 mmHg and after the fibrin adhesive application reached 104±11.96 (P<0.002). In the Suture 2 group, the mean arterial pressure sustained by the suture reached 83±2.67 mmHg and after the cyanoacrylate adhesive application reached 152±14.58 mmHg (P<0.002). Intraluminal adhesive penetration has not been noticed. Conclusion: There was a significant rise in the bursting pressure when tissue adhesives were used as adjacent to arterial suture, and this rise was higher if the cyanoacrylate adhesive was used. In addition, the adhesives do not penetrate through the suture line into the arteries.

Clinical effect of platelet rich fibrin in the treatment of periodontal intrabony defects. systematic review and meta-analysis

Background: There is currently no gold standard biomaterial for the treatment of periodontal intrabony defects (PIDs). One of the current options is the use of platelet-rich fibrin (PRF). Objective: To determine the clinical effect of PRF in the treatment of PID through a systematic review and meta-analysis. Materials and Methods: A literature search was conducted up to February 2017 in the following biomedical databases: Pubmed, Embase, Scielo, Science Direct, SIGLE, LILACS and in the Cochrane Central Register of Clinical Trials. The selection criteria included: randomized clinical trials published in the last 5 years, reporting clinical effects (probing depth, clinical insertion level or gingival recession), with a follow-up time equal to or greater than 6 months, and sample size larger than or equal to 10 patients reporting the use of PRF as a treatment for PID. The methodological quality of the studies was analyzed using the Cochrane Handbook of Systematic Reviews of Interventions as a reference. Results: The search strategy yielded 20 articles. A reduction in probing depth and an increase in clinical insertion level or a reduction in gingival recession is reported, when using PRF alone or in combination with another biomaterial or substance that stimulates tissue regeneration. Conclusion: The literature suggests that the use of PRF in the treatment of PIDs has a beneficial clinical effect when compared to control treatments.

Membrana de fibrina versus injerto conectivo como tratamiento de recesión gingival / Fibrin membrane versus connective tissue graft as gingival recession treatment

RESUMEN: Este caso clínico de boca dividida a 6 meses tiene como objetivo comparar los resultados obtenidos con una membrana de fibrina rica en plaquetas y leucocitos (L-PRF) y un injerto de tejido conectivo (ITC) en el tratamiento de recesiones gingivales clase1 de Miller en un paciente con biotipo gingival grueso. El resultado muestra que el uso de una membrana de L-PRF provee un parcial cubrimiento de la recesión y un menor malestar subjetivo del paciente cuando se compara con el ITC. Sin embargo, el ITC proporciona un mayor porcentaje de cubrimiento radicular y un mejor resultado estético que la membrana de L-PRF al cabo de 6 meses.

ABSTRACT: The aim of this split-mouth clinical study, covering a 6 month period, is to compare the results obtained from Leucocyte and Platelet Rich Fibrin Membrane (L-PRF) and Connective Tissue Grafting (CTG) in the treatment of class 1 Miller gingival recessions in a patient with thick gingival biotype. The results show that the use of L-PRF membrane provides partial coverage of the recession, as well as lower subjective patient discomfort when compared with CTG. However, CTG provides a higher percentage of root coverage and better aesthetic results than the L-PRF membrane after a period of 6 months.

Uso da fibrina rica em plaquetas na implantodontia / The use of the platelet-rich fibrin in Implantology ­ a literature review

Objetivo: realizar uma revisão da literatura acerca do uso do PRF na Implantodontia nos últimos anos, abordando artigos científicos recentes. Material e métodos: foi realizada uma busca na base de dados PubMed, ente os meses de setembro e outubro de 2016, utilizando a associação das palavras-chave na língua inglesa "PRF" e "dental implants". Posteriormente, foi feita uma complementação nas bases de dados Scielo e Google Acadêmico com os mesmos termos na língua portuguesa. Resultados: dez artigos foram selecionados, uma vez que os mesmos respeitavam os critérios de inclusão, incluindo metodologia detalhada, número significativo de pacientes e realização de procedimentos relacionados à instalação de implantes dentais. Todos os estudos avaliados reportaram alguma vantagem no uso do PRF, principalmente em relação ao ganho ósseo. No entanto, todos os estudos apresentaram limitações e apontaram a necessidade de estudos subsequentes com adequada padronização. Conclusão: após a revisão destes estudos, foi possível concluir que o PRF pode ser indicado como adjuvante nos procedimentos de enxertia e na instalação de implantes, e também pode ser utilizado como barreira mecânica em procedimentos em que esta manobra seja necessária para o sucesso final do procedimento de enxertia.

Objective: the aim of the study was to review the literature concerning the use of the PRF in Implantology in the past few years, taking into account the recent articles published in relation to this subject. Material and methods: a search was made on the PubMed (Medline) database, between September and October of 2016, with the terms "PRF" and "dental implants" and also a complementary search in Scielo and Google Academic databases, with the correspondent terms in Portuguese. Results: ten articles were included in the study, once they fulfill the inclusion criteria revealing a detailed methodology, a significant number of patients and with procedures related to the installation of dental implants. All studies evaluated reported some advantage concerning the use of the PRF, mostly in relation to the gain in the bone level. However, all studies also declared limitations of their methodologies and pointed to the necessity in the development of further studies with standard protocols. Conclusion: after revision of the mentioned articles, it was possible to conclude that the PRF can be used as an adjuvant in the grafting procedures and in the dental implant installation, also, can be used as a mechanical barrier in procedures that this kind of barrier is necessary to ensure success in the grafting procedure.

Tratamento da osteonecrose mandibular medicamentosa usando a fibrina leucoplaquetária autóloga ­ Dez meses de acompanhamento sem recidiva / Treatment of medicamentous mandibular osteonecrosis through autologous leukocyte platelet-rich fibrin ­ a 10 months follow-up without signs of recurrence

Uma paciente do sexo feminino, com 72 anos de idade e exposição óssea intraoral, portadora de osteoporose, fazia uso de bifosfonatos há mais de cinco anos. Na região posterior mandibular direita havia osso exposto, hiperemia dos tecidos moles e exsudato purulento. A região mandibular anterior mostrava drenagem de secreção purulenta. Como havia necessidade de cirurgia de fêmur por recomendação médica, a paciente foi submetida à medicação específica (amoxicilina 500 mg, metronidazol 400 mg) e irrigação local com clorexidina 0,12%. Seis meses depois, e mediante os exames de TCFC e CTx sérico, foi realizada a terapia com fibrina leucoplaquetária autóloga. Estas biomembranas foram colocadas nas áreas de osso necrótico. Depois de 15 dias, observou-se uma grande exposição da área operada. Porém, clinicamente, já se notava neovascularização. Após 30 dias, havia grande epitelização da área que se encontrava exposta anteriormente. O caso foi controlado por mais 30 dias, totalizando 60 dias, podendo ser observada uma grande cobertura de tecido mole bem vascularizada e queratinizada na região. As terapias propostas para tratamento não apresentam eficácia suficiente para serem consideradas como protocolos. Dentro dos limites deste relato, a utilização da fibrina leucoplaquetária autóloga apresentou-se favorável como alternativa após dez meses e sem recidivas, abrindo perspectivas para tratar as necroses induzidas por estes medicamentos.

A 72 years-old female patient presented with intraoral bone exposure, osteoporosis, and bisphosphonate use (> 5 years). Also, at the posterior mandible, there was soft tissue hyperemia and pus. On the other hand, the anterior mandible presented with purulent drainage. Due to the need of a hip replacement by medical recommendation, the patient was submitted to specific pharmacological regimen (Amoxicillin 500 mg, Metronidazole 400 mg), and 0.12% chlorhexidine rinses. Six months later, and after CBCT and seric CTx exams, the autologous leukocyte platelet-rich fibrin therapy was applied. These biomembranes covered areas of necrotic bone. After 15 days, there was great exposition at the surgical area. However, neovascularization was clinically observed followed 30 days later by epithelization of previously exposed areas. The case was controlled for more 30 days, where well-vascularized and keratinized soft tissue coverage was identified. The proposed therapy does not provide efficacy to be considered as protocols. However, within the limits of this presentation, the autologous leukocyte platelet-rich fibrin seems to be favorable as an alternative and after 10 months no complications were observed. This opens new perspectives to treat bisphosphonate induced bone necrosis.