Rozprawy doktorskie: „Fibring”

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Nair, Vineet. "On Extending BDI Logics". Thesis, Griffith University, 2003. http://hdl.handle.net/10072/365892.

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In this thesis we extend BDI logics, which are normal multimodal logics with an arbitrary set of normal modal operators, from three different perspectives. Firstly, based on some recent developments in modal logic, we examine BDI logics from a combining logic perspective and apply combination techniques like fibring/dovetailing for explaining them. The second perspective is to extend the underlying logics so as to include action constructs in an explicit way based on some recent action-related theories. The third perspective is to adopt a non-monotonic logic like defeasible logic to reason about intentions in BDI. As such, the research captured in this thesis is theoretical in nature and situated at the crossroads of various disciplines relevant to Artificial Intelligence (AI). More specifically this thesis makes the following contributions: 1. Combining BDI Logics through fibring/dovetailing: BDI systems modeling rational agents have a combined system of logics of belief, time and intention which in turn are basically combinations of well understood modal logics. The idea behind combining logics is to develop general techniques that allow to produce combinations of existing and well understood logics. To this end we adopt Gabbay's fibring/dovetailing technique to provide a general framework for the combinations of BDI logics. We show that the existing BDI framework is a dovetailed system. Further we give conditions on the fibring function to accommodate interaction axioms of the type G [superscript k,l,m,n] ([diamond][superscript k] [superscript l] [phi] [implies] [superscript m] [diamond][superscript n] [phi]) based on Catach's multimodal semantics. This is a major result when compared with other combining techniques like fusion which fails to accommodate axioms of the above type. 2. Extending the BDI framework to accommodate Composite Actions: Taking motivation from a recent work on BDI theory, we incorporate the notion of composite actions, [pi]-1; [pi]-2 (interpreted as [pi]-1 followed by [pi]-2), to the existing BDI framework. To this end we introduce two new constructs Result and Opportunity which helps in reasoning about the actual execution of such actions. We give a set of axioms that can accommodate the new constructs and analyse the set of commitment axioms as given in the original work in the background of the new framework. 3. Intention reasoning as Defeasible reasoning: We argue for a non-monotonic logic of intention in BDI as opposed to the usual normal modal logic one. Our argument is based on Bratman's policy-based intention. We show that policy-based intention has a defeasible/non-monotonic nature and hence the traditional normal modal logic approach to reason about such intentions fails. We give a formalisation of policy-based intention in the background of defeasible logic. The problem of logical omniscience which usually accompanies normal modal logics is avoided to a great extend through such an approach.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Information Technology
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Nair, Vineet, i n/a. "On Extending BDI Logics". Griffith University. School of Information Technology, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20030929.095254.

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In this thesis we extend BDI logics, which are normal multimodal logics with an arbitrary set of normal modal operators, from three different perspectives. Firstly, based on some recent developments in modal logic, we examine BDI logics from a combining logic perspective and apply combination techniques like fibring/dovetailing for explaining them. The second perspective is to extend the underlying logics so as to include action constructs in an explicit way based on some recent action-related theories. The third perspective is to adopt a non-monotonic logic like defeasible logic to reason about intentions in BDI. As such, the research captured in this thesis is theoretical in nature and situated at the crossroads of various disciplines relevant to Artificial Intelligence (AI). More specifically this thesis makes the following contributions: 1. Combining BDI Logics through fibring/dovetailing: BDI systems modeling rational agents have a combined system of logics of belief, time and intention which in turn are basically combinations of well understood modal logics. The idea behind combining logics is to develop general techniques that allow to produce combinations of existing and well understood logics. To this end we adopt Gabbay's fibring/dovetailing technique to provide a general framework for the combinations of BDI logics. We show that the existing BDI framework is a dovetailed system. Further we give conditions on the fibring function to accommodate interaction axioms of the type G [superscript k,l,m,n] ([diamond][superscript k] [superscript l] [phi] [implies] [superscript m] [diamond][superscript n] [phi]) based on Catach's multimodal semantics. This is a major result when compared with other combining techniques like fusion which fails to accommodate axioms of the above type. 2. Extending the BDI framework to accommodate Composite Actions: Taking motivation from a recent work on BDI theory, we incorporate the notion of composite actions, [pi]-1; [pi]-2 (interpreted as [pi]-1 followed by [pi]-2), to the existing BDI framework. To this end we introduce two new constructs Result and Opportunity which helps in reasoning about the actual execution of such actions. We give a set of axioms that can accommodate the new constructs and analyse the set of commitment axioms as given in the original work in the background of the new framework. 3. Intention reasoning as Defeasible reasoning: We argue for a non-monotonic logic of intention in BDI as opposed to the usual normal modal logic one. Our argument is based on Bratman's policy-based intention. We show that policy-based intention has a defeasible/non-monotonic nature and hence the traditional normal modal logic approach to reason about such intentions fails. We give a formalisation of policy-based intention in the background of defeasible logic. The problem of logical omniscience which usually accompanies normal modal logics is avoided to a great extend through such an approach.

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Pinto, Ana Carolina Basso Engler. "Efeitos da fibrina rica em plaquetas e leucócitos (L-PRF) associada ou não a enxerto ósseo bovino na cicatrização de defeitos ósseos em ratas com osteoporose induzida por ovariectomia". Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/58/58138/tde-29082017-164640/.

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Tem sido proposto que a Fibrina Rica em Plaquetas e Leucócitos (L-PRF) pode estimular a neoformação óssea e melhorar a incorporação de enxertos ósseos. Este estudo avaliou a cicatrização de defeitos de tamanho crítico (DTCs) criados em calvária de ratas com osteoporose induzida por ovariectomia e tratados com L-PRF associada ou não a enxerto ósseo bovino (XENO). 32 ratas foram divididas em 4 grupos (n=8): C, PRF, XENO e PRF-XENO. Todos os animais foram submetidos a um procedimento de ovariectomia bilateral no início do estudo. Após 3 meses, DTCs de 5 mm de diâmetro foram criados na calvária dos animais. No grupo C, o defeito foi preenchido apenas com coágulo sanguíneo. Nos grupos PRF e XENO, os defeitos foram preenchido com 0,02 mL de L-PRF e 0,02 mL de XENO, respectivamente. No grupo PRF-XENO o defeito foi preenchido com uma mistura de 0,02 mL de PRF e 0,02 mL de XENO. Todos os animais foram submetidos à eutanásia aos 30 dias pós-operatórios. Foram realizadas análises histomorfométrica, microtomográfica e imunohistoquímica. Os dados obtidos foram estatisticamente analisados (ANOVA, Tukey, p < 0,05). O Grupo PRF-XENO apresentou maior quantidade de osso neoformado (ON) quando comparado ao Grupo XENO, bem como maiores expressões de Fator de Crescimento Endotelial Vascular (VEGF), Osteocalcina (OCN) e Proteína Morfogenética Óssea (BMP)-2/4 (p < 0,05). O Grupo PRF apresentou maior quantidade de ON e maiores expressões de VEGF, OCN, BMP-2/4 e Fator de transcrição relacionado a Runt 2 (RUNX-2) quando comparado ao Grupo C (p < 0,05). Conclui-se que a L-PRF pode favorecer a neoformação óssea de DTCs e potencializar a cicatrização de XENO em ratas com osteoporose induzida por ovariectomia.
It has been proposed that Platelet Rich Fibrin and Leukocyte (L-PRF) can stimulate bone neoformation and improve bone graft incorporation. This study evaluated the healing of critical caliber defects (CSDs) created in the calvaria of rats with osteoporosis induced by ovariectomy and treated with L-PRF associated or not with bovine bone graft (XENO). 32 rats were divided into 4 groups (n = 8): C, PRF, XENO and PRF-XENO. All animals underwent a bilateral ovariectomy procedure at the start of the study. After 3 months, CDSs of 5 mm diameter were created in calvaria of the animals. In group C, the defect was filled only with blood clot. In the PRF and XENO groups, the defects were filled with 0.02 mL of L-PRF and 0.02 mL of XENO, respectively. In the PRF-XENO group the defect was filled with a mixture of 0.02 mL of PRF and 0.02 mL of XENO. All animals were submitted to euthanasia at 30 postoperative days. Histomorphometric, microtomographic and immunohistochemical analyzes were performed. The data were statistically analyzed (ANOVA, Tukey, p < 0.05). The PRF-XENO group presented higher amount of neoformed bone (NB) when compared to the XENO group, as well as higher expression of Vascular Endothelial Growth Factor (VEGF), Osteocalcin (OCN) and Bone Morphogenetic Protein (BMP -2/4 (p < 0.05). The PRF group presented higher amounts of NB and higher expression of VEGF, OCN, BMP-2/4 and Runt-related transcription factor 2 (RUNX-2) when compared to the group C (p <0.05). It can be concluded that L-PRF can improve bone neoformation in CSDs and potentiates the healing of XENO in rats with osteoporosis induced by ovariectomy.

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Garcia, gonzalez Xabel. "Influence de la nature du fibrinogène sur la structure et la mécanique du caillot de fibrine". Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAI076/document.

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La formation du caillot de ﬁbrine, processus clé de la coagulation sanguine, implique la polymérisation des monomères de ﬁbrine en un réseau de ﬁbres. Ce réseau contrôle les propriétés mécaniques du caillot et constitue le squelette sur lequel se base la cicatrisation. Si l’influence des conditions de réaction (pH, concentration, …) est bien connue, le rôle de la composition du fibrinogène sur la structure de la fibrine est inexploré. Cet aspect pourrait être important pour les pathologies cardiovasculaires qui présentent toutes une structure de fibrine anormale.Nous avons étudié la relation entre la composition de plusieurs fibrinogènes et les propriétés structurelles nano- et micro-métriques ainsi que la mécanique des caillots de fibrine. La composition en protéines co-purifiées de ces fibrinogènes a peu d’influence, alors que le profil de polydispersité contrôle la structure multi-échelle de la fibrine. Des mesures de diffusion des rayons x, de spectrophotométrie multi-longueur d’ondes et de microscopie confocale ont mis en évidence que les fibres provenant des fibrinogènes monodisperses sont quasi-cristallines, droites et rigides. Les fibres provenant de fibrinogènes polydisperses sont, elles, beaucoup moins organisées, courbées, avec un module de rigidité faible. Enfin, les propriétés mécaniques de la fibrine ont montré que la réponse des caillots aux déformations, aussi que les scenarios de rupture, sont directement liés à sa structure et donc significativement dépendants du profil de polydispersité des fibrinogènes. Ces résultats ouvrent de nouvelles perspectives dans plusieurs domaines, que ce soit pour l’utilisation optimale des fibrinogènes pour les dysfibrinogénémies et hémorragies, mais également pour la reconstruction tissulaire, ainsi que la compréhension du lien entre la structure anormale des caillots et les maladies cardiovasculaires
Fibrin clot formation is one of the major processes leading to blood clotting. It involves the polymerization of ﬁbrin monomers into a network of ﬁbrin ﬁbres. This network controls the mechanical properties of the clot and serves as a skeleton for wound healing. Environmental factors (pH, concentration, …) have been proved to influence polymerization, however the role of fibrinogen composition on the structure of fibrin remains unexplored. This aspect might be important for the case of cardiovascular pathologies, which present abnormal fibrin structures.We have determined the relation between different sources of fibrinogen with the nano- and micro-metric structural and mechanical properties of fibrin clots. The composition in co-purified proteins of the fibrinogens has no significant importance, however the polydispersity profile controls the multiscale properties of fibrin. Indeed, x-ray scattering, multi-wavelength spectrophotometry and confocal microscopy measurements have proved that fibres from monodisperse fibrinogens are quasi-crystalline, straight and rigid. Fibres from polydisperse fibrinogens are less organised, curbed and less rigid. Finally, the mechanical properties of fibrin showed that the response of clots to deformation, as well as the scenarios of rupture are closely related to the structure, and consequently related to the profiles of polydispersity. This opens outstanding perspectives in many fields such the optimisation of fibrinogen’s use on dysfibrinogenemias or haemorrhages, tissue regeneration or the understanding between the abnormal structure of clots and cardiovascular diseases

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Padovan, Luís Eduardo Marques. "Implante de adesivo fibrínico (Tissucol) em alvéolos dentais de ratos tratados com varfarina sódica após irrigação com ácido épisilon-aminocapróico (EACA) : análise histológica /". Araçatuba, 2002. http://hdl.handle.net/11449/101073.

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Orientador: Tetuo Okamoto
Resumo: Este estudo avaluoi-se o proceso de reparo de feridas de extração dental após irrigação com solução a 5% de ácido epsilon-amino-capróico (EACA) e implante de adesivo fibrínico (Tissucol). Foram utilizados 60 ratos (Wistar), machos, com peso entre 250 gramas e 300 gramas e divididos em 03 grupos com 20 animais cada, onde foram realizados os seguintes procedimentos: No grupo 1 foi administrado 0,1 ml/100mg de peso corporal de solução salina a 0,9%, iniciando-se 06 dias antes da exodontia, administração diária de 0,03ml de varfarina sódica sendo mantida durante todo o experimento. Após a exodontia do incisivo superior direito, seus alvêolos foram preenchido com adesivo fibrinico, No grupo III, os animais desse grupo receberam os mesmos procedimentos dos animais do grupo IIe, após a exodontia, tiveram seus alvêolos irrigados com 5ml de solução a 5% de ácido epsilon-amino-capróico e também preenchidos com adesivos fibrinico (Tissucol)...(Resumo completo, clicar acesso eletrônico abaixo)
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Wang, Kun. "Development of new fibrin-based biomaterials". Electronic Thesis or Diss., Sorbonne université, 2021. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2021SORUS430.pdf.

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La fibrine est largement utilisée en clinique mais les hydrogels formés à partir de cette protéine souffrent généralement d’une faible tenue mécanique et d’une biodégradation très rapide. Pour palier ces limites, nous avons développé trois stratégies. La première consiste à former des matériaux hybrides en ajoutant différentes sources de silice. Une étude en conditions diluées a montré que certains silanes pouvaient favoriser la fibrillogénèse et conduire à une stabilisation des gels. A plus forte concentration de silane ou en présence de silice condensée, l’auto-assemblage de la fibrine est perturbé. La deuxième approche implique l’ajout de nanocristaux de cellulose. Des études en conditions diluées ont mis en évidence l’adsorption du fibrinogène sur les nanocristaux, qui facilite leur alignement. En conditions plus concentrées, un renfort mécanique notable a pu être constaté. De plus un ralentissement de la cinétique de gélification a conduit à de nouvelles formulations injectables. La troisième approche repose sur l’association avec du collagène de type I. En utilisant un procédé de gélification du fibrinogène en conditions acides, il a été possible d’obtenir des gels mixtes mais les propriétés rhéologiques ont été peu modifiées. Pour les trois stratégies adoptées, les matériaux ont été évalués pour leur capacité à promouvoir la prolifération de cellules myoblastes et leur différentiation. Des résultats intéressants ont été obtenus en présence de nanocelullose. Ce travail a donc permis d’élucider les interactions de la fibrine avec différents partenaires inorganiques ou bio-organiques et ouvre de nouvelles perspectives pour son application dans le domaine biomédical
Fibrin is widely used in clinic, but hydrogels formed by this protein generally suffer from poor mechanical property and very rapid biodegradation. To overcome these limitations, we have developed three strategies. The first was to form hybrid materials by adding different sources of silanes. The certain silanes at low concentration could promote fibrillogenesis and lead to stabilization of the gels. At a higher concentration of silane or in the presence of condensed silica, the self-assembly of fibrin is disturbed. The second approach involved the addition of cellulose nanocrystals. Studies under dilute condition shown the adsorption of fibrinogen to the nanocrystals, which facilitates their alignment. Composite hydrogels from high concentrated fibrinogen and nanocrystals showed a notable mechanical reinforcement. In addition, a slowing down of the gelation kinetics have led to new injectable formulations. The third approach was to form the interpenetrate network with type I collagen. Through the process of gelation of fibrinogen under acidic conditions, it was possible to obtain mixed gels but the rheological properties of which were little modified. For the three strategies adopted, the materials have been shown to have the ability to promote proliferation and differentiation of myoblast cells. Interesting results have been obtained in the presence of cellulose nanocrystals. This work has therefore made it possible to elucidate the interactions of fibrin with various inorganic or bio-organic fillers and opens up new perspectives for its application in the biomedical field

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Rezende, Antonio Roberto da Rosa. "Comparação entre uso de cola biológica de fibrina e drenagem de aspiração pós-operatória na prevenção de hematoma e seroma em ritidoplastia : um estudo controlado, randomizado e duplo cego". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2018. http://hdl.handle.net/10183/179691.

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Este trabalho tem por objetivo comparar a eficácia da cola biológica de fibrina e da drenagem de aspiração pós-operatória na prevenção de complicações cirúrgicas como hematoma e seroma após a realização de ritidoplastia pela equipe da Clínica Rezende no Hospital Moinhos de Vento, na cidade de Porto Alegre/RS. Realizou-se estudo prospectivo, controlado, randomizado e duplo cego. Foram analisadas 72 pacientes, divididas em dois grupos de 36, sendo que no grupo dreno utilizou-se drenagem de aspiração e no grupo cola utilizou-se cola de fibrina. Quarenta e oito horas após a realização dos procedimentos, todas as pacientes foram submetidas a aferição ecográfica da lâmina de exsudato presente sob os retalhos cutâneos da face. O volume total médio foi de 3,21 mL no grupo dreno e 1,02 mL no grupo cola, com magnitude de efeito de 68,1% e intervalo de confiança de 55,3 a 77,2 e p <0,001. Com esses resultados, comprovou-se que a cola apresenta eficácia significativa, demonstrando que sua utilização é 68,1 % mais efetiva que a drenagem de aspiração na prevenção de hematomas ou seromas em ritidoplastia.
This study aimed to compare the efficacy of fibrin glue and suction drainage in preventing postoperative complications such as hematoma and seroma following rhytidoplasties conducted by the staff of Clínica Rezende at Hospital Moinhos de Vento in Porto Alegre, Brazil. A prospective, controlled, randomized, double-blind trial was conducted. The 72 patients assessed in the study were divided into two groups of 36 each, one treated with suction drainage and other with fibrin glue. Forty-eight hours after the procedures, all patients underwent ultrasound evaluation of the volume of exudate under facial skin flaps. The average volume of exudate was 3.21 mL in the drainage group and 1.02 mL in the fibrin glue group, with a size effect of 68.1%, 95% confidence interval of 55.3 to 77.2, and p <0.001. The results of this investigation significant favor the use of fibrin glue, showing that was 68.1 % more effective than suction drainage in preventing hematoma or seroma following rhytidoplasty.

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Barcelos, Fabricio Chies. "Histologia comparativa das alterações medulares provocadas pela reparação da dura-máter em ratos". Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5140/tde-04082010-172034/.

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A durotomia acidental, na cirurgia da coluna lombar, é uma das mais comuns complicações, com uma prevalência de 1 a 17%. As fraturas da coluna também podem apresentar-se com lesão dural, chegando a 19% nas fraturas tipo explosão da coluna torácica ou lombar com lesão associada da lâmina vertebral. Procurou-se avaliar as alterações medulares que ocorreram apos a reparação de lesão dural com pontos do tipo simples, com cola de fibrina e com colágeno bovino, através de análise histológica. Manteve-se um grupo controle, sem reparação. Utilizaram-se 70 ratos da raça Wistar, sendo que 34 foram excluídos por problemas anestésicos ou intra-operatórios. Mantiveram-se nove ratos por grupo. Abordaram-se os segmentos vertebrais T8 e T9, para efetuar a lesão, que foi reparada pelos três diferentes métodos avaliados. Os animais permaneceram confinados por 24 dias, sendo submetidos à eutanásia com a coleta de material para análise histológica. O Serviço de Patologia avaliou e graduou (ausente, discreto, moderado e acentuado) os casos quanto à hiperemia, degeneração medular, necrose e infiltrado celular. De forma geral, as técnicas de reparo apresentaram resultados com maior grau de alteração, principalmente em relação ao infiltrado celular, onde todas as técnicas mostraram resultados bem piores. A sutura apresentou graus mais severos de necrose, hiperemia e infiltrado celular. A membrana de colágeno apresentou resultados com graus mais elevados de alteração em relação à hiperemia, à degeneração da substância nervosa e ao infiltrado celular. A reparação com cola de fibrina apresentou piora em relação ao grau de necrose e de infiltrado celular. A presença de alterações medulares em todos os grupos, até mesmo no grupo controle, levou a cogitar algumas possíveis causas para os resultados: as alterações medulares seriam geradas pela técnica cirúrgica ocorrendo uma lesão iatrogênica medular, mas sem repercussão clinica; os materiais estudados poderiam causar alterações no tecido neural; o simples contato do tecido neural com o meio extra-dural, após a lesão, seria a causa das alterações levando à mesma cascata de alterações que ocorre nas lesões medulares traumáticas. Apesar de todos os grupos apresentarem alterações medulares, ficou evidente que as de maior intensidade ocorreram nos grupos que utilizaram materiais de fechamento dural. Os métodos de reparação dural ainda não são os ideais, mas existe o consenso que a lesão deve ser reparada sempre na forma aguda, a fim de evitar e prevenir complicações e seqüelas.
This study aimed to evaluate spinal cord alterations after dural repair with: simple interrupted suture, collagen membrane or fibrin glue using histopathogical analysis. All activities were performed in the São Paulo University Medical School General Hospital Traumatology and Orthopedic Division. Seventy Wistar rats were used, but 34 were excluded due to anesthetic or surgery problems. Animals were kept isolated for 24 days, then killed and histological samples collected. Pathology Division assessed and graduated hyperemia, spinal cord degeneration, necrosis and cellular infiltration. Repair techniques provided higher alteration, mostly in cellular infiltration. Suture showed more severe necrosis, hyperemia and cellular infiltrates graduations. Collagen membrane provided higher alterations related to hyperemia, nerve degeneration and cellular infiltrates. Fibrin glue reparation had worse results in necrosis and cellular infiltrates graduation.Spine cord alterations in all groups, including control group, made us suppose possible reasons for the results: spine cord changes would be caused by surgical technique as iatrogenic injury, without clinical meaning; studied material would cause alterations in neural tissue; contact of neural tissue with extra dural environment, after injury, leading to the same mechanisms present in spinal cord traumatic injury. Despite all groups showed spinal cord alterations it was clear a higher intensity of injury when dural closing material were used. There is no ideal choice for dural repair material and more research is warranted to find better form of repairing dura mater.

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Lima, Patricia Rodrigues de. "Biopolímero de Fibrina como arcabouço biológico para células-tronco mesenquimais como potencial produtor osteogênico". Botucatu, 2019. http://hdl.handle.net/11449/182206.

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Orientador: Rui Seabra Ferreira
Resumo: Desenvolvido em 1990 por um grupo de pesquisadores do Centro de Estudo de Venenos e Animais Peçonhentos (CEVAP), no Estado de São Paulo, Brasil, o Biopolímero de Fibrina (BPF) possuía o principal objetivo de ser um adesivo à base de fibrina sem o uso de sangue humano, a fim de evitar a transmissão de doenças infecciosas por meio deste insumo. Após diversas pesquisas com o BPF, comprovou-se não somente sua capacidade adesiva, como também sua ação coagulante, sua ação como auxiliar no reparo ósseo e cartilaginoso e sua função como arcabouço para células-tronco mesenquimais (CTMs), devido ao fato de que o BPF possui uma estrutura tridimensional adequada. Em estudos recentes e ao exercer essa função, tal material não afetou o microambiente biológico das células, ou seja, permitiu a adesão, proliferação e diferenciação celular, e aderência e crescimento destas. Tais características, apresentadas pelo BPF, são desejáveis na maioria dos biopolímeros utilizáveis, o que ressalta a importância do aprofundamento das pesquisas com BPF e suas interações em experimentos in vivo. Assim, no capítulo 1 realizamos uma ampla revisão na literatura sobre biopolímeros de fibrina, células-tronco e reparação de tecido ósseo. No capítulo 2 é apresentado o artigo científico “Arcabouço de fibrina para células-tronco mesenquimais como potencial osteogênico”.
Abstract: Developed in 1990 by a group of researchers from the Center for the Study of Venomous and Poisonous Animals (CEVAP) in the State of São Paulo, Brazil, the Fibrin Biopolymer (GMP) had the main objective of being a fibrin-based adhesive without the use of human blood in order to avoid the transmission of infectious diseases by means of this input. After several investigations with BPF, it was verified not only its adhesive capacity, but also its coagulant action, its action as an aid in bone and cartilage repair and its function as a framework for mesenchymal stem cells (MSCs), due to the fact that the BPF has an adequate three-dimensional structure. In recent studies and in carrying out this function, such material did not affect the biological microenvironment of the cells, that is, it allowed cell adhesion, proliferation and differentiation, and adhesion and growth of these cells. These characteristics, presented by BPF, are desirable in most usable biopolymers, which underscores the importance of deepening GMP research and its interactions in in vivo experiments. Thus, in Chapter 1 we conducted a broad review in the literature on biopolymers of fibrin, stem cells and repair of bone tissue. In chapter 2 the scientific paper "Fibrin scaffold for mesenchymal stem cells as osteogenic potential" is presented.
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Yeromonahos, Christelle. "Nanostructure des fibres de fibrine". Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00639435.

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La formation d'un caillot de fibrine, processus clé de la coagulation sanguine, implique la polymérisation des monomères de fibrinogène en un réseau de fibres de fibrine. Bien que ce réseau contrôle l'ensemble des propriétés mécaniques du caillot et constitue le squelette sur lequel se base la reconstruction des tissus, sa structure aux échelles inférieures au micron est très mal caractérisée. Nous avons démontré que l'analyse du spectre de lumière visible transmis à travers un caillot permet de déterminer simultanément, quantitativement et en conditions quasi-physiologiques, plusieurs paramètres essentiels de cette nanostructure, à savoir le rayon et la concentration interne en protéines des fibres. Cette méthode de spectrophotométrie a montré le caractère extraordinairement poreux de ces fibres et comment l'environnement de la réaction (concentrations en fibrinogène, en thrombine, température, force ionique) influe sur leur dimension et leur porosité. Cette méthode a ensuite permis de caractériser les effets respectifs sur cette structure de différentes molécules anti-coagulantes, montrant l'action spécifique de l'enoxaparine par rapport aux héparines non-fractionnées et au pentasaccharide. Enfin, nous avons construit un prototype à vocation hospitalière (spectrophotomètre) afin d'étudier la cinétique de polymérisation de la fibrine, non seulement en système purifié en combinaison avec nos spectres de diffusion de rayons X, mais également sur des plasmas de patients présentant des troubles de l'hémostase. Des discussions sont en cours avec un laboratoire pharmaceutique afin d'intégrer cette méthode sur des appareils de diagnostic.

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Herranz-Trillo, Fatima. "Disentangling structural complexity in proteins by decomposing SAXS data with chemometric approaches". Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT044/document.

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De nombreux systèmes biologiques sont intrinsèquement polydispersés, présentant de multiples espèces coexistantes, de taille, de forme ou de conformation différentes (c'est-à-dire, mélanges oligomèriques, des complexes faiblement liés se dissociant en composantes individuelles ou des espèces apparaissant lors de processus amyloïdogéniques). L'étude de tels systèmes complexes est une tâche difficile en raison de l'instabilité des espèces concernées, de leurs concentrations relatives faibles et interdépendantes et des difficultés rencontrées pour l'isolation des composantes pures. Dans cette thèse, j'ai développé des approches méthodologiques pour appliquer la diffusion des rayons X aux petits angles (SAXS), une technique de biologie structurale, à l'étude de systèmes polydispersés. SAXS est une technique additive et par conséquent, le diagramme de diffusion mesuré pour un échantillon polydispersé correspond à la somme pondérée en concentration des contributions de chacune des composantes individuelles du mélange. Cependant, la décomposition des données de SAXS en des spectres spécifiques des espèces et de leurs concentrations relatives est extrêmement laborieuse et ambigue. Dans cette thèse, je présente d'abord une approche objective pour solidement décomposer les jeux de données de SAXS en composantes individuelles. Cette approche adapte la méthode chimiométrique « Multivariable Curve Resolution Alternate Least Squares » (MCR-ALS) aux spécificités des données de SAXS. Notre méthode permet une décomposition rigoureuse et robuste des données de SAXS en introduisant simultanément différentes représentations de ces données et par conséquent, en mettant l'accent sur des changements moléculaires à différentes plages de temps et de résolution structurale. Nous avons appliqué cette approche, que nous appelons COSMiCS (Analyse structurelle objective complexe des systèmes multi-composants) pour étudier deux systèmes polydispersés: la fibrillation des protéines, et les fluctuations conformationnelles de protéines grâce à l'analyse de données obtenues à l'aide d’une technique de couplage de chromatographie d'exclusion de taille (SEC) avec le ligne de SAXS (SEC-SAXS). L'importance d'étudier les processus de fibrillation réside dans leur implication dans des pathologies amyloïdogéniques telles que les maladies de Parkinson ou d'Alzheimer. Il existe de fortes indications que les espèces oligomériques solubles, et non les fibrilles matures, sont la cause principale de la cytotoxicité et des dommages neuronaux. Cette observation souligne l'importance de caractériser les premiers stades des processus de fibrillation. Notre approche COSMiCS a permis d'étudier les processus amyloïdogéniques de l'insuline et du mutant familial E46K de l'α-synucléine, une protéine associée à la maladie de Parkinson. Cette analyse permet la caractérisation structurale des espèces présentes (y compris les espèces oligomériques) et la caractérisation cinétique de leurs transformations.La deuxième partie de la thèse est consacrée à l'utilisation de COSMiCS pour analyser des données de SEC-SAXS. Le SEC-SAXS est extrêmement populaire et a été implémenté sur plusieurs lignes de SAXS à travers le monde. En utilisant des données synthétiques, je démontre la capacité des approches chimiométriques à décomposer des profils chromatographiques complexes. À l'aide de cette approche, j'ai décomposé l’ensemble des données SEC-SAXS mesurés pour la Prolyl OligoPeptidase (POP).En résumé, cette thèse présente une nouvelle approche chimiométrique qui peut être généralement appliquée à tout mélange macromoléculaire pouvant subir une modifacation de son équilibre et pouvant être abordé par SAXS. Les complexes biomoleculaires transitoires, les processus de repliement, les réarrangements structuraux dépendants d’un ligand ou la formation de grands ensembles supramoleculaires peuvent être sondés de façon structurale en utilisant l'approche COSMiCS
Many biological systems are inherently polydisperse, presenting multiple coexisting species differing in size, shape or conformation (i.e. oligomeric mixtures, weakly bound complexes, and species appearing along amyloidogenic processes). The study of such complex systems is challenging due to the instability of the species involved, their low and interdependent relative concentrations, and the difficulties to isolate the pure components. In this thesis, I have developed methodological approaches to apply Small-Angle X-ray Scattering (SAXS), a low-resolution structural biology technique, to the study of polydisperse systems. As an additive technique, the SAXS pattern measured for a polydisperse sample corresponds to the concentration-weighted sum of the contributions from each of the individual components. However, decomposition of SAXS data into species-specific spectra and relative concentrations is laborious and burdened by ambiguity. In this thesis, I present an approach to decompose SAXS datasets into the individual components. This approach adapts the chemometrics Multivariate Curve Resolution Alternating Least Squares (MCR-ALS) method to the specificities of SAXS data. Our method enables the rigorous and robust decomposition of SAXS data by simultaneously introducing different representations of these data and, consequently, emphasizing molecular changes at different time and structural resolution ranges. We have applied this approach, which we name COSMiCS (Complex Objective Structural analysis of Multi-Component Systems), to study two polydisperse systems: amyloid fibrillation by analysing time-dependent SAXSdata, and conformational fluctuations through the analysis of data obtained using on-line size-exclusion chromatography coupled to SAXS (SEC-SAXS). The importance of studying fibrillation processes lies in their implication in amyloidogenic pathologies such as Parkinson’s or Alzheimer’s diseases. There exist strong indications that soluble oligomeric species, and not mature fibrils, are the main cause of cytotoxicity and neuronal damage emphasizing the importance of characterizing early stages of fibrillation. The first application of our COSMiCS approach has allowed the study of the amyloidogenic mechanisms of insulin and the familial mutant E46K of ↵-synuclein, a Parkinson’s disease related protein. The analysis enables the structural characterization of all the species present as well as their kinetic transformations. The second part of the thesis is dedicated to the use of COSMiCS to analyze on-line SEC-SAXS experiments. Using synthetic data, I demonstrate the capacity of chemometric approaches to decompose complex chromatographic profiles. Using this approach, I have studied the conformational fluctuations in prolyl oligopeptidase (POP), a protein related to synaptic functions and neuronal development. In summary, this thesis presents a novel chemometrics approach that can be generally applied to any macromolecular mixture with a tuneable equilibrium that is amenableto SAXS. Transient biomolecular complexes, folding processes, or ligand-dependent structural rearrangements can be probed structurally using COSMiCS

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Cartarozzi, Luciana Politti 1987. "Utilização do selante de fibrina combinado com células tronco mesenquimais no reparo de nervos periféricos através da técnica de tubulização = Use of fibrin sealant combined with mesenchymal stem cells in the repair of peripheral nerves through tubulization technique". [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316368.

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Orientador: Alexandre Leite Rodrigues de Oliveira
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-23T08:37:52Z (GMT). No. of bitstreams: 1 Cartarozzi_LucianaPolitti_M.pdf: 5081962 bytes, checksum: 794c493e497a269465a5b035175dfbcb (MD5) Previous issue date: 2013
Resumo: A regeneração nervosa periférica é um processo complexo dependente do rearranjo e ativação das células de Schwann. O estímulo das células de Schwann pode ser alcançado através do enxerto de células tronco exógenas. Com o intuito de entender a importância do enxerto de células tronco mesenquimais (MSC) no processo regenerativo periférico, utilizamos o modelo de tubulização do nervo isquiático. As próteses tubulares foram preparadas a partir de membranas de poli-caprolactona (PCL) e preenchidas com selante de fibrina (FG), utilizado, neste caso, como substrato para as MSC. A técnica de tubulização foi feita em ratas fêmeas Lewis adultas, divididas em 4 grupos (n = 5 por grupo): normal, PCL (tubo vazio); FG (tubo preenchido com selante de fibrina) e FG+MSC (tubo preenchido com selante de fibrina e enxertado com MSC). Sessenta dias após lesão, os nervos regenerados foram processados para imunoistoquímica e microscopia de luz. A presença de MSC GFP-positivas foi detectada nos nervos dos animais que receberam enxerto de MSC, indicando que a sobrevivência, a longo prazo, das células tronco no tecido. A regeneração axonal, analisada por imunoistoquímica, revelou expressão de elementos básicos do nervo periférico, ou seja, componentes dos axônios e da lâmina basal tiveram a expressão equivalente em todos os grupos experimentais. A organização axonal foi observada através da marcação anti-neurofilamento. A presença das células de Schwann foi analisada através da marcação anti-S100 e o anticorpo anti-colágeno IV foi utilizado para detecção da lâmina basal. A imunomarcação anti-p75NTR, o receptor de baixa afinidade para neurotrofinas, foi utilizada para investigar a reatividade das células de Schwann. A marcação basal deste, em nervos não lesionados, foi aumentada pelo processo regenerativo, sendo estatisticamente maior no grupo FG+MSC (77% em relação ao nervo contralateral; p<0.001). Além disso, houve colocalização de MSC GFP-positivas e imunomarcação anti-BDNF, evidenciando uma possível via de atuação das células sobre o comportamento das células de Schwann. A partir da análise das secções semi-finas dos nervos pudemos avaliar que a área dos nervos regenerados no interior das próteses tubulares foi estatisticamente igual nos diferentes grupos experimentais. Quando quantificamos o número de axônios mielinizados por uma área fixa, o grupo FG+MSC apresentou maior densidade de axônios em relação ao grupo controle (25%, p<0,05). Da mesma maneira, quando analisamos os parâmetros morfométricos nos diferentes grupos experimentais, o grupo FG+MSC apresentou uma tendência a apresentar axônios de maior calibre e bainha de mielina mais espessa, em relação aos demais grupos, sendo que, a EBM, no intervalo de 1,46 a 2,25?m, foi significantemente maior em relação aos grupos PCL e FG (p<0,05). Como consequência, os animais do grupo FG+MSC mostraram recuperação motora significativamente maior na sétima e oitava semana de análise do índice funcional do nervo fibular. Os achados deste estudo mostram que as MSC enxertadas conjuntamente com selante de fibrina influenciam positivamente o processo regenerativo, modulando a reatividade das células de Schwann
Abstract: Peripheral nerve regeneration is a complex process that is dependent on the rearrangement and activation of Schwann Cells (SC). Such stimulation of SCs may be achieved by the use of exogenous stem cells. In order to better understand the importance of mesenchymal stem cell (MSC) grafting in the peripheral regeneration process we have used the model of sciatic nerve tubulization. Tubular prostheses were prepared from polycaprolactone (PCL) membranes and filled with fibrin sealant (FS), which was used as a substrate for the MSC. The technique of tubulization was applied in adult Lewis female rats that were divided into four groups (n = 5 per group): normal, PCL (empty tube), FS (tube filled with fibrin sealant) and FS + MSC (tube filled with fibrin sealant and grafted with MSC). Sixty days after injury, the regenerated nerves were processed for imunohistochemistry and observed under fluorescence microscopy. The presence of GFP positive stem cells was detected in the nerves of the animals that received MSC grafts, indicating the long term survival of such cells. The axonal regeneration process was studied by immunohistochemistry and revealed the presence of the basic elements of the peripheral nerve, namely axons and basal lamina components that were equivalent in all experimental groups. The axonal organization was observed with anti-neurofilament immunostaining. The presence of SCs was analyzed with anti-S100 immunostaining and anti-type IV collagen was used to detect the basal lamina. Anti-p75NTR, the low affinity receptor for neurotrophins, was used to investigate the reactivity of the SCs. A basal positive labeling in uninjured nerves was detected, which was upregulated by the regenerative process, being statistically higher in FS + MSC group (77% relative to uninjured nerve; p<0.001). Moreover there was colocalization between GFP-positive MSC and anti-BNDF immunolabeling, showing a possible pathway that these cells induce the reactivity of SCs. From sciatic nerve semi-thin sections we were able to evaluate that the areas of regenerated nerves were statistically the same in the different experimental groups. When we quantified the number of myelinated axons in 50.000?m2, the FG+MSC group showed higher density of axons when compared with PCL group (25%, p<0,05). In the same way, the analysis of morphometric parameters showed that the FG+MSC group have a tendency to present higher caliber axons and ticker myelin sheath when compared with other groups, being that the myelin sheath thickness, in the interval between 1,46 to 2,25?m, was significantly higher in FG+MSC group when compared to PCL and FG (p<0,05). As the functional result of the findings above, the FG+MSC animals showed higher motor function recovery, analyzed by FFI, at seventh and eighth weeks after lesion. The findings herein show that MSC associated with the FS scaffold improve the regeneration process by positively modulating the reactivity of SCs
Mestrado
Biologia Celular
Mestra em Biologia Celular e Estrutural

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Resende, Margarida Reynolds de Sousa. "Utilização de laser ou de fibrina rica em plaquetas no maneio de feridas do membro distal equino". Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2019. http://hdl.handle.net/10400.5/18819.

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Dissertação de Mestrado Integrado em Medicina Veterinária
As feridas do membro distal equino que cicatrizam por segunda intenção, são potencialmente de cicatrização lenta. O objetivo do estudo consistiu na avaliação do efeito terapêutico do laser ou da aplicação de fibrina rica em plaquetas (PRF) na cicatrização de feridas por segunda intenção de membros distais de equinos e de etiologia traumática, em comparação com o método convencional na prática clínica. Todas as feridas (n=9) possuíram diferentes dimensões iniciais e tempos desde a sua lesão até à primeira observação clínica. Consideraram-se três grupos: o grupo controlo (pomada tópica + penso); o grupo laser (terapia do laser + penso); e o grupo PRF (PRF + penso). As feridas foram fotografadas e medidas, com posterior cálculo das suas áreas diárias (retangular e elítica) e da sua taxa de cicatrização. Na análise estatística utilizou-se o teste de variância unifatorial (one-Way ANOVA) e o teste post-hoc de Duncan, com significância de P<0,05. A taxa de cicatrização foi superior no grupo laser em relação aos grupos controlo e PRF (P<0,05), mas semelhante entre o grupo PRF e o grupo controlo. Em conclusão, este estudo preliminar sugere a continuação de trabalhos de estudo em feridas do membro distal do cavalo utilizando laser e PRF numa maior amostragem e em condições controladas.
ABSTRACT - LASER OR PLATELET-RICH FIBRIN APPLICATION ON MANAGEMENT OF EQUINE DISTAL LIMB WOUNDS - Equine distal limb wounds that are left to heal by second intention are potentially slow healing. This study evaluated the therapeutic effect of laser or the application of platelet-rich fibrin (PRF) in wound healing by second intention of distal limbs of horses and of traumatic etiology, in comparison with the conventional method in clinical practice. All wounds (n = 9) had different initial dimensions and times since their injury until their first clinical observation. Three groups were considered: the control group (topical ointment + dressing); laser group (laser therapy + dressing); and the PRF group (PRF therapy + dressing). The wounds were photographed and measured, with subsequent calculation of their daily areas (rectangular and elliptical) and their healing rate. In the statistical analysis, a one-way ANOVA and a post hoc comparison test (Duncan test) were used, with significance of P < 0.05. The healing rate was higher in the laser group compared to the control and PRF groups (P < 0.05), but similar between the PRF group and the control group. In conclusion, this preliminary study suggests the continuation of studies on wounds of the distal limb of the horse using laser and PRF therapies in a larger sampling and under controlled conditions.
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Malzoni, Carolina Mendonça de Almeida. "Utilização da fibrina rica em plaquetas e leucócitos (L-PRF) em procedimentos cirúrgicos de elevação do assoalho do seio maxilar /". Araraquara, 2020. http://hdl.handle.net/11449/192532.

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Orientador: Daniela Leal Zandim-Barcelos
Resumo: A fibrina rica em plaquetas e leucócitos (L-PRF) é um derivado plaquetário autógeno capaz de liberar citocinas e fatores de crescimento favoráveis ao reparo tecidual. Por esta razão a L-PRF vem sendo utilizada em diversos procedimentos odontológicos. Uma das aplicabilidades clínicas da L-PRF é em procedimentos de levantamento do seio maxilar, uma técnica já consagrada na odontologia que permite a colocação de implantes dentários em região posterior de maxilas atróficas. Para avaliar a efetividade do uso da L-PRF, dois estudos clínicos independentes foram realizados utilizando a L-PRF em seios maxilares. Um deles teve o propósito de avaliar a influência da L-PRF na regeneração óssea quando associada ao osso mineral bovino desproteinizado (OBD) em procedimentos de elevação do assoalho do seio maxilar, e o outro teve o propósito de avaliar a efetividade da L-PRF no reparo de membranas de Schneider acidentalmente perfuradas durante o procedimento de levantamento do seio maxilar. Para isso, o primeiro trabalho foi um estudo clínico randomizado controlado envolvendo 19 pacientes com edentulismo na região posterior de maxila. De forma aleatória, 24 seios maxilares destes 19 pacientes foram distribuídos entre os grupos teste e controle. O grupo teste abordou 12 seios maxilares que foram enxertados com OBD associado à L-PRF, já o grupo controle abordou outros 12 seios maxilares enxertados apenas com OBD. Após 8 meses de reparo, uma biópsia foi obtida por meio de broca trefina no mesmo... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Platelet and leukocyte-rich fibrin (L-PRF) is an autogenous platelet derivative capable of releasing cytokines and growth factors favorable to tissue repair. For this reason, LPRF has been used in several dental procedures. One of the clinical applicabilities of L-PRF is in maxillary sinus lifting procedures, a technique already established in dentistry that allows the placement of dental implants in the posterior region of atrophic jaws. To assess the effectiveness of using L-PRF, two independent clinical studies were conducted using L-PRF in maxillary sinuses. One of them had the purpose of evaluating the influence of L-PRF in bone regeneration when associated with deproteinized bovine mineral bone (DBB) in maxillary sinus floor elevation procedures, and the other had the purpose of evaluating the effectiveness of L-PRF in the repair of Schneider membranes accidentally perforated during the maxillary sinus lifting procedure. For this, the first study was a randomized controlled clinical study involving 19 patients with edentulism in the posterior region of the maxilla. At random, 24 maxillary sinuses of these 19 patients were distributed between the test and control groups. The test group involved 12 maxillary sinuses that were grafted with DBB associated with L-PRF, whereas the control group addressed 12 other maxillary sinuses grafted only with DBB. After 8 months of repair, a biopsy was obtained using a drill bit on the same axis of insertion of the implants. The biopsie... (Complete abstract click electronic access below)
Mestre

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Sathananthan, Saranya. "Modulating fibrin matrix properties via fibrin knob peptide functionalized microgels". Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44905.

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Fibrin is the body's natural provisional matrix activated in response to vascular injury in which noncovalent knob:hole interactions between fibrin monomers lead to the assembly of fibrin for clot formation. In this study we aimed to exploit fibrin knob:hole affinity interactions with swelling, space filling microgels for the development of a potential bio-synthetic hybrid polymer system with hemostatic properties. Previous work has explored the inherent binding interactions of various fibrin knobs and their complementary polymerization holes, which have led to the development of fibrin knob peptide mimic (GPRPFPAC) with enhanced binding affinity for fibrin(ogen) holes. By coupling this enhanced fibrinogen binding peptide with a pNIPAm microgel system capable of being dynamically tuned and self-assembled, we hypothesized the specific and rapidly triggered formation of a bulk hydrogel in a wound environment (i.e. in the presence of fibrinogen). We found that at the peptide ligand density and concentrations of microgels used, that a rapid formation of a gel did not occur in the presence of fibrinogen alone. However with fibrinogen and thrombin, we found that fibrin network polymerization, structure, and viscoelastic properties were greatly altered in the presence of knob peptide-conjugated microgels.

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Soon, Allyson Shook Ching. "Exploiting fibrin knob:hole interactions for the control of fibrin polymerization". Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/45917.

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The minimization of blood loss represents a significant clinical need in the arena of surgery, trauma, and emergency response medicine. Fibrinogen is our body's native polymer system activated in response to tissue and vasculature injury, and forms the foundation of the most widely employed surgical sealant and hemostatic agent. Non-covalent knob:hole interactions are central to the assembly of fibrin that leads to network and clot formation. This project exploits these affinity interactions as a strategy to direct fibrin polymerization dynamics and network structure so as to develop a temperature-triggered polymerizing fibrin mixture for surgical applications. Short peptides modeled after fibrin knob sequences have been shown to alter fibrin matrix structure by competing with native fibrin knobs for binding to the available holes on fibrinogen and fibrin. The fusion of such knob peptides to a non-native component should facilitate binding of the fused component to fibrinogen/fibrin, and may permit the concomitant modification of the fibrin matrix. We examined this hypothesis in a three-step approach involving (a) analyzing the ability of tetrapeptide knob sequences to confer fibrin(ogen) affinity on a non-fibrin protein, (b) investigating the effect of knob display architecture on fibrin(ogen) structure, and (c) designing a temperature-responsive knob-displaying construct to modulate fibrin(ogen) affinity at different temperature regimes, thus altering fibrin(ogen) structure.

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Gaspar, Alberto Facury. "Impacto nos resultados assistenciais e nos custos hospitalares do emprego do selante de fibrina na anastomose pancreatojejunal após ressecção duodenopancreática". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17157/tde-28072015-143625/.

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Introdução: Os benefícios do emprego do selante de fibrina no reforço de anastomoses pancreatico-jejunais, após ressecção duodenopancreática, visando a redução da incidência de fístula pancreática pós operatória (FPPO), ainda são questionáveis. Objetivo: Avaliar a influência do emprego do selante de fibrina na anastomose pancreatico-jejunal, após duodenopancreatectomia, na incidência de fístula, bem como suas consequências clínicas e os custos hospitalares. Metodologia: Estudo retrospectivo de 62 pacientes consecutivos submetidos a duodenopancreatectomia, divididos em dois grupos: 31 pacientes utilizando o selante de fibrina (GCS) e 31 pacientes sem o emprego de selante (GSS). As variáveis estudadas foram agrupadas em epidemiológicas, clínicas, laboratoriais, com destaque para a incidência de fístula pancreática, classificada segundo a definição do International Study Group on Pancreatic Fistula, suas complicações pós operatórias catalogadas segundo a classificação de Clavien e suas repercussões na assistência e nos seus custos avaliados pelo método de absorção com rateio simples de todas as despesas, exceto a despesa com medicamentos, tratada de forma separada. Resultados: Os grupos foram homogêneos para os parâmetros epidemiológicos, clínicos, e laboratoriais e não foram registradas diferenças significativas na comparação da evolução pós operatória e dos indicadores assistenciais hospitalares. Por outro lado, os custos hospitalares foram mais elevados no GCS, em relação ao GSS (p<0,0001). Conclusão: O emprego do selante de fibrina, no reforço da anastomose pancreatico-jejunal, em pacientes submetidos a duodenopancreatectomias, nas condições estudadas, não melhorou os resultados clínicos e assistenciais e ainda aumentou os custos hospitalares.
Introduction: The benefits of fibrin sealant employment in strengthening pancreatico-jejunal anastomosis after duodenopancreatic resection, reducing the incidence of pancreatic fistula postoperative (PFPO) are still questionable. Objective: To evaluate the influence of the use of fibrin sealant in pancreatico-jejunal anastomosis after pancreaticoduodenectomy in the incidence of fistula and its clinical consequences and hospital costs. Methodology: A retrospective study of 62 consecutive patients who underwent pancreaticoduodenectomy, divided into two groups: 31 patients using fibrin sealant (GCS) and 31 patients without the sealant employment (GSS). The variables were grouped into epidemiological, clinical, laboratory, especially the incidence of pancreatic fistula classified as defined by the International Study Group on Pancreatic Fistula, their postoperative complications cataloged according to Clavien rating and its repercussions on care and its costs assessed by the absorption method with simple apportionment of all expenses except the expenditure on medicines, treated separately. Results: The groups were homogeneous for clinical, epidemiological and laboratory parameters and no significant differences were recorded in the comparison given postoperative progress and hospital assistance indicators. Moreover, hospital costs were higher in GCS, with respect to GSS (p <0.0001). Conclusion: The use of fibrin sealant in pancreatojejunal anastomosis after pancreaticoduodenectomy, in the studied conditions, did not improve the results of care and also increased hospital costs

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Alexaline, Maïa. "Elaboration d’un épiderme de culture et évaluation non clinique sur un modèle de brûlure cutanée". Thesis, Paris 11, 2015. http://www.theses.fr/2015PA114816.

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Les brûlures cutanées graves dont les lésions profondes et étendues des tissus ne permettent pas d’envisager un traitement classique par autogreffes, bénéficient aujourd’hui de substituts épidermiques autologues pour leur recouvrement. En effet l’ingénierie tissulaire permet l’obtention d’épiderme de culture autologue (CEA) par l’amplification in vitro de kératinocytes à partir d’une petite biopsie de peau saine. Si ces CEAs ont permis la survie de nombreux patients depuis les années 1980, ils n’en restent pas moins largement perfectibles du point de vue de l’esthétique et de la fonctionnalité de l’épiderme et de la jonction dermo-épidermique régénérés mais aussi en termes de coûts et de prévention des zoonoses.Ainsi, ce travail de thèse s’inscrit dans le cadre d’une recherche translationnelle et porte sur l’élaboration d’un épiderme de culture par ingénierie tissulaire en vue d’une application clinique chez les grands brûlés, afin de favoriser la cicatrisation et la régénération épidermique. Ce travail porte également sur l’évaluation non clinique de notre substitut épidermique sur un modèle animal de brûlure cutanée.Après avoir développé un nouveau substitut épidermique sur fibrine de plasma humain (hPBES : human Plasma-Based Epidermal Substitute), nous avons procédé à l’évaluation détaillée de ses caractéristiques phénotypiques et fonctionnelles en comparaison au substitut épidermique de référence Epicel® (Genzyme, US). Nous avons montré des propriétés plus intéressantes en termes de clonogénicité et de caractère souche, de prévention de la différenciation, de prolifération, de potentiel de migration, et de conservation des protéines de la membrane basale avec notre produit par rapport à Epicel®.L’apport de la matrice de fibrine de plasma sur la culture des kératinocytes en comparaison à une matrice de fibrine issue de fibrinogène purifié et à une culture sans matrice a été étudié notamment sous l’angle des facteurs libérés par les matrices. Nous avons observé une amélioration des propriétés des substituts épidermiques par la fibrine : diminution de la différenciation terminale, augmentation du potentiel migratoire et sécrétion de facteurs pro-cicatrisants (GM-CSF et PDGF-BB). En outre, la fibrine de plasma améliore spécifiquement la morphogénèse épidermique, la prolifération kératinocytaire et la clonogénicité.Le procédé de culture de ce nouveau substitut a été adapté aux exigences réglementaires sans altération du potentiel régénératif: remplacement des cellules nourricières murines par des fibroblastes dermiques humains, adaptation du milieu de culture et sécurisation du plasma par traitement à l’amotosalen.Toutes les étapes d’un modèle de brûlure chez le rat nude reproduisant la technique chirurgicale employée pour la greffe de CEA ont été mises au point, mais un rejet du greffon épidermique n’a pas permis l’évaluation d’hPBES sur ce modèle. Nous avons donc évalué le substitut épidermique développé hPBES chez la souris NOD-SCID après greffe au fascia et mis en évidence une bonne prise de greffe épidermique permettant la régénération d’un épiderme humain aux caractéristiques proches d’une peau saine avec une réorganisation de la jonction dermo-épidermique des 2 semaines après greffe
The deep and large injuries caused by massive burns prevent the use of split-thickness skin autografts. Today, autologous epidermal substitutes constitute an alternative treatment for skin regeneration. In fact tissue engineering allows the production of Cultured Epithelial Autografts (CEA) by in vitro keratinocyte amplification from a small healthy skin biopsy. The clinical use of CEA since the 1980’s has allowed an increase in the survival rate of burnt patients. However, CEAs present numerous drawbacks, among them the high fragility of keratinocyte sheets, and the immaturity of the dermal-epidermal junction leading to heavy cosmetic and functional sequelae.This thesis focuses on the bioengineering of epidermal substitute for clinical burn treatment to enhance wound healing and skin regeneration, from a translational research point of view. This work also includes the development of an animal model of third degree burn for the evaluation of epidermal substitute.We first developed a new epidermal substitute cultured on a fibrin matrix from human plasma (hPBES: human Plasma-Based Epidermal Substitute). Then we characterized this new substitute with phenotypical and functional analyses, using as a reference the epidermal substitute Epicel® (Genzyme, US). We observed properties more favorable with hPBES than with Epicel® in terms of clonogenicity, stemness, differentiation level, proliferation, migration potential and basement membrane protein conservation.The influence of the plasma-based fibrin matrix on keratinocytes was studied in comparison with a culture on a fibrin from purified fibrinogen, and with a culture with no matrix. For this study we focused our analysis on the role of the released factors from fibrin matrices during epidermal substitute culture. Both fibrin matrices improved epidermal substitute properties: reduction of terminal differentiation, enhancement of migration potential, secretion of wound healing enhancing factors. Besides, plasma-based fibrin specifically promote epidermal morphogenesis, keratinocyte proliferation and clonogenicity.The culture process was adapted to European regulation requirements without diminishing its regenerative potential: substitution of murine feeder cells by human dermal fibroblasts, adaptation of culture medium and plasma viral inactivation using amotosalen treatment.A burn model including all the surgical steps used in clinics for CEA grating was developed on nude rats. However the evaluation of hPBES on this model could not be achieved due to graft rejection. Therefore we evaluated epidermal regeneration after hPBES graft on acute wounds on NOD-SCID mice. We showed a good graft rate, with the regeneration of a human epidermis close to healthy epidermis with a well-organized dermal-epidermal junction two weeks after hPBES grafting

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Goczkowski, Mathieu. "Conception et élaboration de matériaux à biodégradabilité contrôlée pour la médecine régénérative". Thesis, Cergy-Pontoise, 2017. http://www.theses.fr/2017CERG0920.

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Les gels de fibrine présentent un fort intérêt en médecine régénérative, puisqu’ils miment la matrice temporaire créée lors de la cicatrisation. Cependant, quand préparés à concentration physiologique, ils ne sont pas manipulables, ni conservables à sec. Pour contrer ces désavantages, ils peuvent être associés à un autre réseau de polymères, dans une architecture de Réseaux Interpénétrés de Polymères (RIP). Cette approche a été utilisée pour associer à un réseau de fibrine, un coréseau semi-synthétique d’albumine de sérum bovin (BSA) et de poly(oxyde d’éthylène) (POE), obtenu par photopolymérisation de BSA et PEG modifiés avec des fonctions méthacrylate (BSAm, PEGDM).Il a été démontré par des tests ex vivo et in vitro que ces matériaux ont de multiples applications potentielles, puisqu’ils supportent à leur surface, la croissance de nombreux types cellulaires. De plus, il a été observé que ces matériaux peuvent servir comme vecteurs pour la délivrance de molécules d’intérêt thérapeutique.La technologie a d’ailleurs été optimisée, en utilisant non plus des précurseurs modifiés avec des fonctions méthacrylate, mais acrylate. Cette modification a permis de réduire la toxicité du procédé de synthèse, tout en conservant les performances des matériaux. Il a également été démontré que divers matériaux optimisés ont des mécanismes de dégradation différents, et contrôlables par leur formulation initiale.Enfin, deux nouvelles familles de RIPs à base de fibrine ont été développées, en associant à un réseau de fibrine, un autre réseau de protéine, la fibroïne de soie. Des RIPs parfaitement manipulables ont été obtenus, supportant à leur surface la culture de fibroblastes. Ces matériaux sont donc prometteurs pour l’ingénierie tissulaire de la peau et d’autres applications
Fibrin gels are of interest in regenerative medicine, as they mimic the provisory matrix synthesized during wound healing process. However, when prepared at physiologic concentration, these gels cannot be handled, nor stocked in dry state. To face these drawbacks, they can be associated with another polymer network, in an Interpenetrating Polymer Network (IPN). This strategy was used to associate to a fibrin network, a semi-synthetic conetwork composed of bovine serum albumin (BSA) and poly(ethylene oxide) (PEO), obtained by photopolymerization of methacrylate-modified BSA and PEG.It was demonstrated through ex vivo and in in vitro experiments that these materials have numerous potential applications, as they support on their surface, the culture of numerous cell types. Moreover, it was observed that they may be used as drug carrier for drug release applications.Moreover, the technology was optimized by modifying the methacrylate functions on the precursors for acrylate functions. This modification allowed to reduce the toxicity of the process, while preserving materials performances. It was also demonstrated that these optimized materials have different degradation mechanisms, which are controllable by their initial formulation.Finally, 2 new groups of fibrin-based IPNs were developed, by associating to a fibrin network, another protein network, the silk fibroin. Perfectly handable IPNs were obtained, which support on their surface the culture of fibroblasts. These materials are then very promising for skin tissue engineering, and most likely other applications

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Allan, Peter. "Microrheology of fibrin clots". Thesis, University of Leeds, 2012. http://etheses.whiterose.ac.uk/3042/.

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An active particle tracking microrheology technique has been developed to study the viscoelastic properties of human fibrin and plasma clots. In order to perform microrheology measurements, a magnetic microrheometer device has been adapted and a technique developed, following the procedure of Evans et al., to measure the frequency dependent viscoelastic moduli (G() and G()). This technique has been supported by complementary investigation methodologies, such as protein analysis, turbidity, and multiple microscopy techniques. As a result of this study new insights into the viscoelastic dynamics of fibrin have been revealed. Three stress relaxation mechanisms, as predicted by Morse et al. for networks of semi-flexible fibres, were observed and occur on distinctly different timescales. The scaling of the tension dominated contribution was measured to scale as G ~ c2.7 0.2 in agreement with the prediction of Mackintosh. The presence of FXIII resulted in stiffer less deformable clots but was found to have no effect on the viscoelastic dynamics of clots. Frequency measurements of the loss tangent revealed that on timescales intermediate between stress relaxation modes clots were much more susceptible to permanent deformation. The effect of fibrinogen, thrombin and calcium on the viscoelastic behaviour of clots was also investigated. Increased fibrinogen levels produced clots which displayed predominantly elastic behaviour on shorter time-scales. The molecular mechanism underpinning the role of fibrinogen γ in fibrin clot polymerisation, structure and viscoelasticity was also investigated. We report new data which show that fibrinogen γ is associated with the formation of mechanically weaker, non-uniform clots composed of thinner fibres. This is caused by direct disruption of protofibril formation by and not through thrombin inhibition or binding to FXIII. In addition, the effects of the plasma proteins FVIIa, FIXa, FXIIa and FXIII on clot properties are also reported.

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Purves, Maud. "The D-domain of fibrin : structural and functional studies". Doctoral thesis, University of Cape Town, 1987. http://hdl.handle.net/11427/27202.

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The D-domain of fibrin (ogen) was separated from the parent molecule by plasmin digestion in the presence of calcium and isolated by means of DEAE-anion exchange chromatography followed by gel-filtration in buffer containing 4 M urea. Fluorescent-D-dimer (f-D-dimer) was isolated from a plasmic digest of fibrin clotted in the presence of 2.45 mM dansyl cadaverine, a fluorescent lysine analogue. Fluorescent-D-monomer was a by-product of f-D-dimer purification, the yield being determined by the concentration of dansyl cadaverine. At 2.45 mM f-D-monomer was always present in the digest. The f-D-monomer is probably formed directly and not as a result of degradation of f-D-dimer. The molecule elutes in the fibrinogen-derived-D- monomer position on gel-filtration. A protease was isolated and partially purified from venom of the puffadder (Bitis arietans). Puffadder venom protease is characterized by its ability to cleave D-dimer into symmetrical D-monomers, smaller than plasmin-derived D-monomers from fibrinogen. This characteristic was used to detect the puffadder venom protease activity with fluorescent-D-dimer being used as the substrate. Fractions obtained were assayed for D-dimer cleavage activity and the samples analyzed by means of SDS-PAGE on 4-20% gradient gels under reducing (βME) and non-reducing conditions. The fluorescent bands were located under U.V light and photographed prior to staining with Coomassie Blue. Several methods for the purification of the protease were investigated.

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Oliveira, Guilherme José Pimentel Lopes de [UNESP]. "Efeito da raspagem com laser de Er, Cr:YSGG nas superfícies radiculares: estudos in vitro". Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/95386.

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Foram utilizados 60 dentes humanos nessa pesquisa. No primeiro experimento, 15 dentes extraídos por doença periodontal foram selecionados para avaliar a influência da irradiação com laser de Er,Cr: YSGG sobre a morfologia e adesão de células sanguíneas sobre as superfícies radiculares. As 60 amostras provenientes desses dentes foram divididos em 3 grupos de acordo com o tipo de tratamento aplicado: Grupo 1- RAR; Grupo 2- Irradiação com laser de Er,Cr: YSGG; Grupo 3- RAR e irradiação com o laser de Er,Cr: YSGG. 10 amostras de cada grupo foram avaliados quanto a adesão de elementos sanguíneos, e as outras 10 amostras foram avaliados quanto a morfologia da superfície radicular por MEV. Os testes de Kruskall-Wallis e Mann-Whitney foram utilizados para avaliar os resultados. Em relação à adesão de elementos sanguíneos, este estudo não demonstrou diferenças estatísticas entre os grupos (p=0.359), a análise morfológica demonstrou que as superfícies radiculares irradiadas com o laser de Er-Cr:YSGG foram mais rugosas que as do grupo controle (G2-G1: p=0.0003 e G3-G1: p=0.0003). No segundo experimento, 20 dentes foram utilizados para avaliar a influência do ângulo de irradiação do laser de Er,Cr:YSGG sobre a rugosidade e o desgaste das superfícies radiculares. Cada face proximal foi dividida em 3 áreas, sendo que a área superior foi tratada com raspagem e alisamento radicular, a área média não foi submetida a nenhum tipo de tratamento e a área inferior foi irradiada com o laser de Er,Cr:YSGG. Os dentes foram divididos em 4 grupos ,com 5 dentes cada, a depender da angulação da aplicação da irradiação do laser de Er,Cr:YSGG na área ( 30º, 45º, 60º, 90º). A rugosidade das áreas foram avaliadas através de um rugosímetro e posteriormente os dentes foram submetidos a processamento histológico...
60 human teeth were used in that research. In the first experiment, 15 extracted teeth for periodontal disease were selected to evaluated the effect of Er,Cr:YSGG irradiation on root surfaces for adhesion of blood components and morphology. 60 root surface specimens were obtained by selecting four from each tooth. Samples were divided into three groups of 20 each, according to treatments. Group 1 (G1) was treated by scaling and root planing (SRP), Group 2 (G2) was irradiated by Er,Cr:YSGG laser and Group 3 (G3) was treated by SRP and Er,Cr:YSGG laser irradiation. Blood was placed on each of 10 specimens from each of the three groups, to evaluate adhesion of blood components to the root surfaces. A morphological analysis was made of the root surfaces of the other 10 specimens from each group by scanning electron microscope (SEM). Statistical processing was done with the Kruskal-Wallis and Mann-Whitney tests. No statistical differences for adhesion of blood components to root surfaces were found between the groups (p = 0.359). However, morphological analysis disclosed that all root surfaces irradiated by Er,Cr:YSGG laser (100%) were rougher than surfaces that were not irradiated (G1-G2: p = 0.0003 and G1-G3: p = 0.0003). In the second experiment, 20 teeth were used to evaluated the effect of the working tip angulations on root roughness and substance removal using Er,Cr:YSGG radiation. The distal and mesial surfaces of each tooth was divided in 3 areas. The upper area was treated with scaling and root planing. The medium area was not submitted to any treatment and the lower area was irradiated with Er,Cr:YSGG laser. The teeh were divided in 4 groups, with 5 teeth each depending the working tip angulations using Er,Cr:YSGG at the lower area (30º, 45º, 60º, 90º).The roughness surfaces were evaluated by a profilometer, and... (Complete abstract, click electronic access below)

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Bidault, Laurent. "D’un matériau innovant vers un pansement actif et un substitut cutané". Thesis, Cergy-Pontoise, 2012. http://www.theses.fr/2012CERG0611/document.

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La peau est un organe à l'architecture complexe qui assure plusieurs rôles essentiels dont celui de barrière contre les agressions extérieures. De plus, il est capable de se régénérer grâce un processus hautement régulé: la cicatrisation. Des biomatériaux, synthétisés à partir de macromolécules d'origine naturelle et/ou synthétique, ont été développés pour servir de pansements, de support de culture cutanée ou de substitut cutané.L'originalité de notre étude a été de mimer, non pas la matrice extracellulaire dermique, mais le réseau de fibrine, temporaire, qui apparait lors de la cicatrisation. Au cours de travaux précédents, il a été démontré qu'il était possible de renforcer mécaniquement un réseau de fibrine, à concentration physiologique, en l'associant, dans une architecture de réseaux interpénétrés de polymères (RIP), avec un réseau de polyoxyde d'éthylène (POE). Durant mes travaux, la non toxicité de ces matériaux envers des cellules modèles a été démontrée. Puis, la composition du matériau a été optimisée pour augmenter son module de stockage jusqu'à un facteur 100 par rapport à celui du gel de fibrine. Ensuite, grâce à la synthèse d'alcool polyvinylique méthacrylate (PVAm) pour le remplacement du POE, un matériau présentant mêmes qualités, mais plus facilement stockable à l'état déshydraté et complètement réhydratable, a pu être obtenu. Nous nous sommes ensuite attachés à rendre ce nouveau matériau biodégradable. L'introduction de sérum albumine bovine méthacrylate (BSAm) copolymérisée avec le PVAm (co-réseau) dans une architecture RIP avec un réseau de fibrine a permis de synthétiser un matériau hydride présentant l'ensemble des propriétés précédemment décrites et dégradable par des enzymes. Ce matériau a été testé en contact avec des populations cellulaires fibroblastiques. Il a pu être démontré, qu'en plus d'être non cytotoxique, ce matériau pouvait être totalement colonisé par ces cellules. Pour finir, l'encapsulation de cellules à l'intérieur de cette matrice et leur prolifération ont pu être observées. En conclusion, les matériaux synthétisés lors de ces travaux, c'est-à-dire des RIPs associant un réseau de fibrine à la concentration physiologique et un réseau de polymère synthétique, possèdent les propriétés nécessaires pour être utilisés en tant que pansements et supports de culture pour la régénération cutanée. De plus, la possibilité d'encapsuler des fibroblastes dans le RIP à base de coréseaux de PVAm et BSAm en fait un substitut cutané potentiel.Mots clefs : hydrogel, réseaux interpénétrés de polymères, fibrine, POE, PVA, BSA, encapsulation cellulaire, fibroblaste, médecine régénérative, peau
The skin is an organ with a complex architecture that provides several key roles including barrier against external aggressions. In addition, it has the ability to regenerate itself by following a highly regulated process,: the wound healing. Biomaterials, synthesized by using macromolecules from natural and/or synthetic origin, have been developed to serve as wound dressing, cell culture support or skin substitute.The originality of our study was to not mimic the dermal extracellular matrix, but mimic the the fibrin scaffold, the temporary matrix who appears during the healing process. In previous work, it was shown that it was possible to mechanically reinforce a fibrin scaffold at physiological concentration by associating into interpenetrating polymer network (IPN) architecture with a polyethylene oxide (PEO) network. In my work, the non-toxicity of these materials was proved with model cells. Then, the material composition has been optimized to increase the storage modulus by 100 in comparison of the fibrin scaffold. Then, through the synthesis of polyvinyl alcohol methacrylate (PVAm) to replace the POE, a material with the same properties, but more easily stored in a dehydrated state (more ductile) and completely rehydratable could be obtained. We then attached to make this new biodegradable material. The use of bovin serum albumin methacrylate (BSAm) copolymerized with PVAm(conetwork) into IPN architecture with a fibrin scaffold performs to synthesize a hybrid material with all the properties described above and degradable by enzymes. This material has been tested in contact with human fibroblast. It has been demonstrated that in addition to be non-cytotoxic, this material could be completely colonized by these cells. Finally, the encapsulation of cells in the bulk of this matrix and their proliferation inside were observed.In conclusion, the materials synthesized in this work, IPN containing a fibrin scaffold at physiological concentration and a synthetic polymer network, have sufficient properties to be used as wound dressings or cells culture support for skin regeneration. In addition, the ability to encapsulate fibroblasts in material based on conetwork of PVAm and BSAM makes it suitable for a skin substitute application.Key words: hydrogel, Interpenetrating Polymer Network, fibrin, POE, PVA, BSA, entrapping, fibroblast, tissue engineering, skin

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Fatah, Kamaran Tahir. "Studies on fibrin gel structure /". Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980608fata.

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Nogueira, Grinia Michelle. "Hidrogeis e filmes de fibroina de seda para fabricação ou recobrimento de biomateriais". [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/267124.

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Orientador: Marisa Masumi Beppu
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica
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Resumo: Hidrogéis e filmes de fibroína de seda foram preparados e caracterizados com o objetivo de avaliar sua potencial aplicação no campo de biomateriais. Hidrogéis foram obtidos durante a etapa de diálise da solução de fibroína de seda e suas propriedades físicas, químicas, citotoxicidade e potencial de calcificação in vitro foram determinados. Esses materiais apresentaram estrutura tridimensional porosa com resistência mecânica à compressão relativamente alta e grande potencial de calcificar in vitro, sendo possíveis candidatos à aplicação na área de regeneração óssea. Filmes de fibroína de seda com quitosana foram preparados utilizando-se a técnica "Layer-by-Layer". Com esta técnica, foi possível depositar filmes anisotrópicos, com fibras alinhadas na superfície de substratos de silício. Como os biopolímeros em estudo são conhecidamente biocompatíveis, o alinhamento de fibras na superfície do substrato poderia ser explorado como um meio de guiar a adesão e proliferação celular ou ainda agregar resistência mecânica a outros filmes poliméricos. Filmes de fibroína de seda foram também empregados para recobrir pericárdio bovino utilizado na fabricação de válvulas cardíacas. Amostras recobertas com fibroína de seda foram avaliadas quanto à sua propensão à calcificação in vitro e os filmes foram testados quanto a sua citotoxicidade e potencial de adesão e crescimento de células endoteliais. Os resultados indicaram que filmes de fibroína de seda não apresentam citotoxicidade, são compatíveis com células endoteliais e não induzem a calcificação do pericárdio bovino recoberto durante os testes in vitro. Assim, o recobrimento com fibroína de seda pode ser uma alternativa de tratamento do pericárdio bovino para funcionalização da sua superfície. Dos resultados apresentados, concluiu-se que tanto hidrogéis como filmes derivados de fibroína de seda podem ser aplicados no campo de biomateriais, sejam como matrizes para reconstituição óssea, ou filmes para recobrimento e funcionalização da superfície de materiais.
Abstract: Silk fibroin hydrogels and films were prepared and characterized in order to investigate their potential application in the biomaterials field. The hydrogels were obtained during the dialysis step and their physical and chemical characteristics, cell toxicity and compatibility and potential to calcify in vitro were investigated. Those materials presented a porous tridimensional structure, mechanical strength and ability to deposit calcium phosphate crystals during in vitro calcification tests; therefore, silk fibroin hydrogels can probably be used in the bone regeneration field. Silk fibroin films were obtained by using the Layer-by-Layer technique. Bidirectional alignment of silk fibroin fibers was designed by adjusting the substrate position during the dipping process. A potential application to films with alignment of fibers is to guide cell adhesion and proliferation, since the biopolymers used to build the films are known as biocompatible materials. Silk fibroin films were also used to coat bovine pericardium used to fabricate cardiac valves. The coated samples were characterized by in vitro calcification tests and biocompatibility of silk fibroin films was evaluated by citotoxicity tests and their ability to adhere and grow of endothelial cells. The results showed that silk fibroin films are biocompatible and do not induce calcification during in vitro calcification tests, being suitable to coatand functionalize bovine pericardium surface. From the presented results, it can be concluded that silk fibroin hydrogels and films are suitable materials to be explored in the biomaterials field, for bone regeneration or biomaterials surface coating.
Doutorado
Engenharia de Processos
Doutor em Engenharia Química

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Deneufchatel, Marie. "Biomatériaux auto-supportés et dégradables pour l'ingénierie tissulaire : association d'un gel de fibrine et un réseau de polymère synthétique". Thesis, Cergy-Pontoise, 2016. http://www.theses.fr/2016CERG0877/document.

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L’ingénierie tissulaire vise à régénérer des organes ou des tissus lésés. Ainsi, les gels de fibrine sont largement utilisés pour la reconstruction de différents tissus. Cependant, à concentration physiologique, ils ne peuvent pas être manipulés. Pour améliorer leurs propriétés mécaniques, ils peuvent être combinés dans une architecture de Réseaux Interpénétrés de Polymères (RIP) à un réseau de polymère synthétique (PVA ou POE). Ces RIPs peuvent être rendus biodégradables en copolymérisant d’albumine bovine de sérum modifiée par des groupements méthacrylate (BSAm) avec le partenaire synthétique.Selon leurs compositions, ces matériaux peuvent être complètement dégradés ou fragmentés après quelques jours en présence de thermolysine, une enzyme protéolytique. Ces cinétiques de dégradation de ces RIPs ont été étudiées en suivant le relargage des fragments protéiques hors du matériau, d’une part, et la diminution de leurs propriétés viscoélastiques, d’autre part. Leur biocompatibilité a été vérifiée : des fibroblastes cultivés à leur surface présentent une viabilité supérieure à 90% après 5 semaines de culture et leur prolifération est suivie de la synthèse de macromolécules de la Matrice Extracellulaire.Afin de leur ajouter une action bactéricide et d’augmenter encore leur résistance mécanique, des sels d’ammonium ont également été incorporés à certains de ces RIPs. Enfin, la synthèse de tels RIP a été mise au point à partir de plasma sanguin. Les éventuels phénomènes de rejet lors de leur intégration au sein du corps devraient ainsi être limités. De plus, le plasma sanguin contenant un grand nombre de facteurs de croissance et de molécules bioactives, la réparation tissulaire devrait ainsi être améliorée
Tissue engineering aims to regenerate deficient tissues and organs. Fibrin gels are widely used for the reconstruction of various tissues. However, at physiological concentration, they can’t be handled. To improve their mechanical properties, they can be combined with a synthetic polymeric network (PVA or PEO) in an Interpenetrating Polymer Network (IPN) architecture. These IPN can be made biodegradable by crosslinking the Bovine Serum Albumin modified by methacrylate groups (BSAm) with the synthetic partner.Depending on the composition, these materials can be fully degraded or fragmented after several days of incubation with thermolysin, a proteolytic enzyme. The degradation kinetics of these hydrogels were studied by following the release of proteic fragments from the material and by the loss of viscoelastic properties. The biocompatibility was also verified: fibroblasts cultivated on the surface show a viability of over 90% after 5 weeks of culture and the proliferation is followed by the synthesis of Extracellular Matrix macromolecules.To add a bactericide property, and to increase their mechanical resistance, ammonium salts were incorporated in those IPN. Lastly, the synthesis of these IPN were adapted, starting from whole blood plasma. Rejection phenomena upon implantation should thus be hindered. Moreover, blood plasma contains a wide variety of growth factors and bioactive molecules, which should improve tissue regeneration

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Ochoa, Clara Cecilia Reyes. "Avaliação da segurança do biopolimero de fibrina como arcabouço para células tronco mesenquimais em lesões na dura-máter em ratos". Botucatu, 2019. http://hdl.handle.net/11449/181183.

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Orientador: Rui Seabra Ferreira Júnior
Resumo: Terapias efetivas de lesões na dura-máter representam um enorme desafio à medicina, devido à dificuldade de suturas com êxito e de vedação das meninges, aumentando os índices de mortalidade e morbidade destes pacientes. Biomateriais que possam favorecer a regeneração e impedir o extravasamento de líquido cefalorraquidiano sem produzir efeitos adversos são alvos da indústria farmacêutica. Este estudo avaliou a biocompatibilidade do Biopolimero de Fibrina (BPF) derivado de peçonha de serpente como arcabouço tridimensional para células-tronco mesenquimais (CTMs) em lesões na dura-máter de ratos wistar (Rattus norvegicus). As CTMs foram caracterizadas na quinta passagem por citometria de fluxo (ICAM, CD90, CD34, CD45, CD11b) e diferenciadas em linhagens osteogênica e adipogênica. Foram utilizados 4 grupos (n=20) de ratos Wistar machos adultos. O grupo C (controle) foi submetido à durotomia. Os grupos tratados foram submetidos à durotomia seguido de: Tratamento com Biopolimero de fibrina (BPF); células-tronco mesenquimais (CTMs); e BPF+CTMs, formado pela associação do Biopolimero de fibrina e células-tronco mesenquimais. As CTMs marcadas e associadas ao BPF foram avaliadas por imageamento da fluorescência in vivo. Os animais foram avaliados neurológica e clinicamente quanto à sensibilidade dolorosa, deiscência de pontos, infecção da ferida, consumo de alimento e água e habilidades motoras. Foram realizadas eutanásias dos animais aos 7 e 28 dias após cirurgia e coletado material pa... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Effective therapies to treat dura mater injuries represents a major challenge to medicine due to its lack of sutures with high seal properties upon meninges, increasing the rate of mortality and morbidity among these patients. Biomaterials that promotes regeneration and prevent extravasation of cerebrospinal fluid, without producing adverse effects, are targets of the pharmaceutical industry. The present study aimed to evaluate the biocompatibility of the use on Fibrin Biopolymer (FBP) derived from snake venom as tridimensional scaffold to mesenchymal stem cells (MSC) on rat’s dura mater injury. Mesenchymal stem cells characterization was performed at fifth passage by flow cytometry (ICAM, CD90, CD34, CD45, CD11b) and differentiated into osteogenic and adipogenic lineages. Four groups (n=20) os male Wistar rats were used. Group C (control) animals were submitted to durotomy only. Treatment groups were submitted to durotomy followed by: Fibrin Biopolymer (FBP); mesenchymal stem cells (MSC); and FBP+MSCs, consisting on the association between fibrin biopolymer and mesenchymal stem cells. Marked MSCs associated to FBP were evaluated through in vivo fluorescence imaging. Animals were evaluated neurologically and clinically regarding pain sensitivity, dehiscence of suture, wound infection, feeding e motor capacity parameters. Animals were euthanized at seven and 28 days after surgical procedure, and biological material was collected to histological and proteomic analysis. Protein ... (Complete abstract click electronic access below)
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Longo, Marco Vinicius Losso. "Influência da adição de células-tronco mesenquimais derivadas de tecido adiposo associadas a conduto de fibrina na regeneração de nervo periférico em modelo experimental de ratos". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5132/tde-21012016-164659/.

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INTRODUÇÃO: O tratamento padrão para lesões de nervo periférico que não podem ser suturados primariamente é a enxertia de nervo autólogo. Esse método, porém, carece de resultados satisfatórios e impõe algumas limitações técnicas e complicações. Várias opções já foram estudadas como alternativas ao enxerto de nervo, porém ainda não há conduto biológico ou sintético disponível para uso clínico que tenha a mesma capacidade regenerativa do enxerto de nervo autólogo. Os avanços em cultura celular e o maior entendimento dos mecanismos moleculares e celulares da regeneração nervosa levaram ao uso de células promotoras de regeneração associado aos condutos na tentativa de melhorar os resultados da reconstrução nervosa. Vários estudos demonstraram que o uso de célulastronco derivadas de tecido adiposo (ADSC) em condutos aloplásticos potencializa a regeneração neural. No entanto, nenhum estudo até hoje comparou a adição de ADSC indiferenciadas em conduto aloplástico ao tratamento padrão com autoenxerto. Esse estudo tem como objetivo avaliar a influência da adição de células-tronco mesenquimais derivadas de tecido adiposo em conduto de fibrina na regeneração de nervo periférico e comparar com enxertia de nervo autógeno em modelo experimental de ratos. MÉTODO: Em um modelo de lesão de nervo ciático (defeito de 10 mm) foram avaliados 30 ratos Wistar divididos em 3 grupos. O defeito de nervo foi reconstruído usando conduto de fibrina (Grupo Conduto, n=10), conduto de fibrina acrescido de ADSC (Grupo ADSC, n=10) e autoenxerto do nervo (Grupo Autoenxerto, n=10). A avaliação funcional dos ratos foi realizada com o teste de marcha (walking track analysis) com 4, 8 e 12 semanas e o índice de função ciática (IFC) foi determinado. Após 12 semanas, o peso do músculo tríceps sural foi avaliado. Segmentos dos nervos regenerados também foram coletados para análises histológicas como densidade axonal e diâmetro médio das fibras. RESULTADOS: O grupo Conduto mostrou recuperação funcional no teste da marcha após a reconstrução do nervo, porém com resultados inferiores aos outros dois grupos. O grupo ADSC mostrou recuperação intermediária e o grupo Autoenxerto obteve os melhores resultados (IFC com 12 semanas de -53,3±.3 vs -44,7±3 vs - 35,6±2, respectivamente, p < 0,001). A relação de peso do músculo tríceps sural no grupo Conduto foi de 41,1±3%, no grupo ADSC de 53,3±4% e no grupo Autoenxerto de 71,0 ± 4% (p < 0,001). Na avaliação histológica, o grupo Conduto mostrou densidade axonal de 39,8±3 axônios/10.995?m2 e diâmetro médio das fibras de 3,9 ± 0?m2, o grupo ADSC densidade axonal de 58,8 ± 3 axônios/10.995um2 e diâmetro médio das fibras de 4,9 ± 1um2 e o grupo Autoenxerto densidade axonal de 67,1±2 axônios/10.995?m2 e diâmetro médio das fibras de 8,9±1um2 (p < 0,001). CONCLUSÃO: A adição de células-tronco mesenquimais derivadas de tecido adiposo (ADSC) em conduto de fibrina na regeneração de nervo periférico, em modelo experimental de ratos, mostrou recuperação funcional e regeneração histológica estatisticamente mais significativa comparada à reconstrução somente com conduto de fibrina, porém ainda aquém dos resultados obtidos com enxertia de nervo autógeno
Introduction: The standard treatment for peripheral nerve injuries that cannot be primarily sutured is nerve autograft. But this method lacks satisfactory results and imposes some technical limitations and complications. Several options have been studied as alternatives to nerve autografting, but there is no biological or synthetic conduit available for clinical use that provides the same regenerative capacity of nerve autograft. Advances in cell culture and understanding of nerve regeneration mechanisms led to the use of regeneration-inducing cells in association with conduits, in an attempt to improve the reconstruction results. Several studies have shown that the use of adipose derived stem cells (ADSC) into conduits enhances neural regeneration. However, there is no study that compared the addition of undifferentiated ADSC in alloplastic conduit to standard treatment with autograft. This study evaluated the influence of the addition of adipose derived stem cell in fibrin conduit for peripheral nerve regeneration in comparison to the nerve autograft, in a rat model. Method: A sciatic nerve injury model (10-mm defect) was performed in 30 Wistar rats, which were divided into 3 groups. Nerve defect was reconstructed using fibrin conduit (Conduit group, n=10), fibrin conduit filled with ADSC (ADSC group, n = 10) and nerve autograft, (Autograft group, n=10). The walking behavior was measured by footprint analysis at 4, 8, and 12 weeks and sciatic function index (SFI) was determined. After 12 weeks, the triceps surae muscle weight was evaluated and histological analysis was performed to evaluate the regenerated nerve and measured axonal density and fibers diameter average. Results: The Conduit group showed less improvement in walking behavior compared to ADSC group and Autograft group (SFI at 12 weeks, - 53.3 ± .3 vs -44.7 ± 3 vs -35.6 ± 2 respectively, p< 0.001). The triceps surae muscle weight ratio of the fibrin conduit group was 41.1± 3%, ADSC group was 53.3 ± 4%, and Autograft group 71.0 ± 4% (p < 0.001). In histological evaluation, the Conduit group showed axonal density of 39.8±3 axons/10995um2 and fiber diameter average of 3.9±0 ?m2, the ADSC group had axonal density of 58.8 ± 3 axons/10995 um2 and fiber diameter average of 4.9±1?m2 and axon density of Autograft group was 67.1±2 axons/10995 um2 and fiber diameter average was 8.9±1?m2 (p < 0.001). Conclusion: The addition of adipose derived stem cells (ADSC) into fibrin conduit used for nerve reconstruction following peripheral nerve injury in the rat model, showed better functional recovery and better histological regeneration compared to reconstruction with fibrin conduit without ADSC. However, the functional recovery in the ADSC group was worse than that in nerve Autograft group and the nerve repair with the ADSC-fibrin conduit has less myelinated fibers when compared to the repair with nerve autograf

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Oliveira, Guilherme José Pimentel Lopes de. "Efeito da raspagem com laser de Er, Cr:YSGG nas superfícies radiculares : estudos in vitro /". Araraquara : [s.n.], 2010. http://hdl.handle.net/11449/95386.

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Orientador: Rosemary Adriana Chiérici Marcantonio
Banca: Márcio Zafalon Casati
Banca: Estela Sasso Cerri
Resumo: Foram utilizados 60 dentes humanos nessa pesquisa. No primeiro experimento, 15 dentes extraídos por doença periodontal foram selecionados para avaliar a influência da irradiação com laser de Er,Cr: YSGG sobre a morfologia e adesão de células sanguíneas sobre as superfícies radiculares. As 60 amostras provenientes desses dentes foram divididos em 3 grupos de acordo com o tipo de tratamento aplicado: Grupo 1- RAR; Grupo 2- Irradiação com laser de Er,Cr: YSGG; Grupo 3- RAR e irradiação com o laser de Er,Cr: YSGG. 10 amostras de cada grupo foram avaliados quanto a adesão de elementos sanguíneos, e as outras 10 amostras foram avaliados quanto a morfologia da superfície radicular por MEV. Os testes de Kruskall-Wallis e Mann-Whitney foram utilizados para avaliar os resultados. Em relação à adesão de elementos sanguíneos, este estudo não demonstrou diferenças estatísticas entre os grupos (p=0.359), a análise morfológica demonstrou que as superfícies radiculares irradiadas com o laser de Er-Cr:YSGG foram mais rugosas que as do grupo controle (G2-G1: p=0.0003 e G3-G1: p=0.0003). No segundo experimento, 20 dentes foram utilizados para avaliar a influência do ângulo de irradiação do laser de Er,Cr:YSGG sobre a rugosidade e o desgaste das superfícies radiculares. Cada face proximal foi dividida em 3 áreas, sendo que a área superior foi tratada com raspagem e alisamento radicular, a área média não foi submetida a nenhum tipo de tratamento e a área inferior foi irradiada com o laser de Er,Cr:YSGG. Os dentes foram divididos em 4 grupos ,com 5 dentes cada, a depender da angulação da aplicação da irradiação do laser de Er,Cr:YSGG na área ( 30º, 45º, 60º, 90º). A rugosidade das áreas foram avaliadas através de um rugosímetro e posteriormente os dentes foram submetidos a processamento histológico... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: 60 human teeth were used in that research. In the first experiment, 15 extracted teeth for periodontal disease were selected to evaluated the effect of Er,Cr:YSGG irradiation on root surfaces for adhesion of blood components and morphology. 60 root surface specimens were obtained by selecting four from each tooth. Samples were divided into three groups of 20 each, according to treatments. Group 1 (G1) was treated by scaling and root planing (SRP), Group 2 (G2) was irradiated by Er,Cr:YSGG laser and Group 3 (G3) was treated by SRP and Er,Cr:YSGG laser irradiation. Blood was placed on each of 10 specimens from each of the three groups, to evaluate adhesion of blood components to the root surfaces. A morphological analysis was made of the root surfaces of the other 10 specimens from each group by scanning electron microscope (SEM). Statistical processing was done with the Kruskal-Wallis and Mann-Whitney tests. No statistical differences for adhesion of blood components to root surfaces were found between the groups (p = 0.359). However, morphological analysis disclosed that all root surfaces irradiated by Er,Cr:YSGG laser (100%) were rougher than surfaces that were not irradiated (G1-G2: p = 0.0003 and G1-G3: p = 0.0003). In the second experiment, 20 teeth were used to evaluated the effect of the working tip angulations on root roughness and substance removal using Er,Cr:YSGG radiation. The distal and mesial surfaces of each tooth was divided in 3 areas. The upper area was treated with scaling and root planing. The medium area was not submitted to any treatment and the lower area was irradiated with Er,Cr:YSGG laser. The teeh were divided in 4 groups, with 5 teeth each depending the working tip angulations using Er,Cr:YSGG at the lower area (30º, 45º, 60º, 90º).The roughness surfaces were evaluated by a profilometer, and... (Complete abstract, click electronic access below)
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Naidoo, Dhesigen P. "Metals and the conformation of fibrin". Master's thesis, University of Cape Town, 1992. http://hdl.handle.net/11427/26555.

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The carboxy terminal of the γ-chain of human fibrinogen contains at least three biologically. important functional domains: (i) the fibrinogen γ-chain polymerisation centre, (ii) the platelet receptor domain and (iii) the site for staphyloccocal clumping. The nature of the site specificity of these interactions necessitates the existence of a preferred conformation for this region, the nature of which has yet to be clearly established. A novel zinc metalloproteinase isolated from puff adder venom (PAV protease) capable of specifically cleaving the di-γ-chain of transglutaminase (Factor XIIIa) catalysed crosslinked plasmin derived D-dimer into apparently symmetrical monomers has been described. The activity is fibrin specific and displays an unusual site specificity for the γ-carboxy terminal domains within the crosslink region. The activity was reported to be potentiated by zinc. The effect of zinc on the digestion of D-dimer by PAV protease was evaluated by SDS-PAGE and by a fluorimetric technique utilising a fluorescent dansylcadaverine conjugate of the substrate (f-D-dimer). A differential zinc binding study determined that the potentiation of activity by zinc was due to a zinc-substrate rather than a zinc-enzyme interaction. The binding constant for zinc to D-dimer was determined by Scatchard analysis of zinc titration data. The interaction of zinc and f-D-dimer was confirmed by fluorescence anisotropy determinations. The nature of the coordination capsule around the metal cation was determined by examining a cobalt-fibrin-D-dimer complex and characterising the difference visible absorption spectrum thereof. The donor ligands from the D-dimer fragment for the metal ion were determined as histidines by examining zinc(II) and cobalt(II) binding to diethylpyrocarbonate modified fibrin-D-dimer and hydroxylamine treated DEPC-fibrin-D-dimer. Through this study it has been established that the PAV protease cleavage of the di-γ-chain of the plasmin derived D-dimer fragment is potentiated by zinc(II) ions through the formation of a novel zinc determined conformation of fibrin-D-dimer. This presents the possibility of a fibrinspecific neo-epitope being manifested in the presence of zinc ions that could provide a means to determine fibrin degradation products more specifically. A model for the neo-epitope has been proposed.

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Corrêa, Maria Elvira Pizzigatti. "Adesivos de fibrina : avaliação clinica e experimental". [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310135.

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Orientadores: Maria Lourdes Barjas-Castro, Joyce Annicchino Bizzacchi
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Os adesivos teciduais são produtos originários de proteínas do plasma humano, utilizados como agentes hemostáticos em diferentes procedimentos cirúrgicos. Objetivos: avaliar a influência da cola de fibrina como agente hemostático local após extrações dentárias em pacientes hemofílicos. Analisar a influência dos adesivos nos processos de reparação tecidual em pele e em alvéolo dentário em modelo animal. Capítulo I Pacientes e Métodos: Foram realizadas extrações dentárias em 31 pacientes hemofílicos, sem prévia terapia de reposição de fatores de coagulação. Os pacientes receberam antifibrinolítico oral (Ipsilon® - 200mg/kg, VO, 8/8 horas, por 7 dias). Foi realizada a avaliação da saúde bucal através dos índices: Gengival (IG); Índice de Placa (IP) e através do Índice CPOD (dentes cariados, perdidos e obturados). Após as extrações os alvéolos foram preenchidos com cola de fibrina autóloga. Os pacientes foram avaliados 24 horas após o procedimento. Resultados: em seis procedimentos (19,4%) foram observados sangramentos que foram controlados com reaplicação da cola de fibrina e dose única de fator de coagulação (um hemofílico grave, 3 hemofílicos moderados e em 2 hemofílicos leves). As médias dos índices IG, IP e CPOD foram, no grupo que sangrou, 1,7; 1,8; e 18 e, no que não apresentou sangramento, 1,8; 1,8; e 19, respectivamente. Conclusão: A cola de fibrina foi efetiva como agente hemostático local após extrações dentárias em pacientes hemofílicos, reduzindo significantemente a terapia de reposição de fatores de coagulação. As condições de saúde bucal, refletidas pelos resultados obtidos através da avaliação dos índices IG, IP e CPOD, demonstraram não haver influência desses fatores na eficácia da cola de fibrina autóloga como agente hemostático local. Capítulo II - Material e Métodos: Vinte e cinco ratos Wistar foram submetidos a duas incisões em dorso de pele após anestesia intramuscular. Na incisão do lado direito, foram inseridas esponjas embebidas em Selante de Fibrina associado ao fator XIII e aprotinina (Beriplast P® - Aventis Beringher) e, na incisão do lado esquerdo, foram inseridas esponjas sem adesivos, como controle. Os animais foram divididos em cinco grupos e sacrificados nos dias 1, 7, 14, 21, e 28 após a cirurgia. O tecido do dorso do animal foi dissecado e preparado blocos para análise microscópica (HE). O estudo histomorfométrico foi realizado em microscópio KS400 (40x - Zeiss, Jena). A composição celular do tecido de granulação foi analisada randomicamente, em 20 campos de cada amostra. Os dados foram estatisticamente analisados usando o Wilcoxon signed rank test. Os resultados mostraram um elevado número de células inflamatórias na periferia do grupo com Selante de Fibrina comparado com o controle. Esses dados sugerem que o Selante de Fibrina induziu uma intensa e prolongada resposta inflamatória no processo cicatricial e que o Selante de Fibrina persistiu até 28 dias após a cirurgia.Capítulo III: Material e Métodos: Setenta e cinco ratos Wistar foram submetidos a extração do incisivo superior após anestesia intramuscular. Os ratos foram divididos em 3 diferentes grupos e os adesivos foram aplicados nos alvéolos. O primeiro grupo (25 ratos) recebeu cola de fibrina, o segundo grupo (25) Selante de Fibrina (Beriplast P® - Aventis Beringher) e o terceiro (25) foi considerado como grupo controle. Os animais foram sacrificados por inalação de éter nos dias 1, 7, 14, e 28 após a cirurgia. Os crânios foram dissecados, submetidos a descalcificação e preparados para análise microscópica (HE). O estudo histomorfométrico foi realizado pelo sistema KS400 (Zeiss,Jena). Neoformação óssea foi cuidadosamente delimitada em quatro regiões alveolares. Os dados foram analisados estatisticamente usando regressão múltipla, ANOVA e Turkey test. Os resultados mostraram que a neoformação óssea (µm2) no grupo controle e com Selante de Fibrina foram estatisticamente similar, entretanto o alvéolo que recebeu a cola de fibrina apresentou menor área de formação óssea comparada com o grupo que recebeu o Selante (p=0,0034). Concluindo, os adesivos defibrina não influenciaram no processo de cicatrização óssea
Abstract: Fibrins adhesives are plasma protein derivate and it has been used in different surgical procedures as a local hemostatic agent. Objectives: Evaluate the autologous fibrin glue as a local hemostatic agent after tooth extraction in hemophilia patients. Analyze the influence of the fibrin adhesives in a tissue healing process in skin and alveolar bone in an animal model. Chapter I: Patients and Methods: Thirty-one hemophilic patients were submitted to teeth extractions using autologous fibrin glue and an oral antifibrinolytic drug (epsilon-aminocaproic acid). Oral health indexes (plaque-PI, gingival-GI and decay-missing-filling-teeth-DMFT index) were evaluated before tooth extraction. Results: Post-surgical bleeding episodes were observed in 6 hemophilic patients (1 severe, 3 moderate and 2 mild type). The media of PI and GI in the bleeding group were 1.8 and 1.7, respectively and in the non-bleeding group 1.8 for both (PI: p=0.8; GI: p=0.56). The global DMFT index was 18 in the bleeding group and 19.6 in the non-bleeding group (p=0.67). Conclusion: The autologous fibrin glue was efficient as a local hemostatic agent after tooth extraction in hemophilia patients. The status of oral health did not interfere in the dental extraction bleeding of hemophilic patients. Chapter II: Material and Methods: Twenty-five Wistar rats were submitted to intramuscular anesthesia. Two incisions were realized on animal back and subcutaneous ventrally pockets were made. Into the right side a vegetal sponge imbibed in FS associated to factor XIII and aprotinina (BeriplastP®-Aventis- Beringher) was introduced and in the left side the sponge without FS was insert as control. Animals were divided in 5 groups and they were sacrificed on days 1, 7, 14, 21 and 28 after the surgery. Animal back tissues were dissected and blocks were prepared for light microscopy study (H&E). The morphometric study was performed by microscopy (KS400)-40x. Twenty randomized fields from each sponge were analyzed and the cellular composition of the granulation tissue was examined with regard to its content of capillaries, granulation tissue cells and inflammatory cells. The data were statistically analyzed using the Wilcoxon signed rank test for the weight differences between the numbers of inflammatory cells for each animal in both groups. The results showed a high number of inflammatory cells in the peripheral area of the FS group comparing with the controls. The results suggest that the FS induced an intense and prolonged inflammatory response in wound healing, and the FS persisted up to 28 days after surgery. Chapter III: Material and Methods: Seventy-five Wistar rats were submitted to a superior incisor extraction after intramuscular anesthesia. The rats were divided into tree different groups and the sealants were introduced into the alveolar bone. The first group (25) received human homemade fibrin glue, the second group (25) FS associated to factor XIII and aprotinin(Beriplast®¿Aventis-Beringher) and the third group (25) was the control. Animals were sacrificed by prolonged diethyl inhalation on days 1, 7, 14 and 28 after surgery. Animal craniums were dissected and submitted to a decalcification, and preparated for H&E light microscopy. The morphometric study was performed by means of an interactive computerized image analysis system KS400(Zeiss, Jena). New bone formation was carefully delimited in four different alveolar regions of each specimen. The data were statistically analyzed using multiple regression, ANOVA and Tukey's test. Results showed that the amount of alveolar bone formation(µm2) in the control group and commercial sealant was statistically similar. However, alveolus receiving homemade sealant presented less amount of new bone formation comparing to commercial sealant and control group (p=0.0034). The present study demonstrated that fibrin adhesives did not influence on the alveolar healing process
Doutorado
Clinica Medica
Doutor em Clínica Médica

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Kumar, Rachana. "On the procoagulant effect of fibrin a resonance loop between fibrin - von Willebrand factor - platelets and thrombin /". [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1997. http://arno.unimaas.nl/show.cgi?fid=5826.

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Cassaro, Claudia Vilalva. "Selante heterólogo de fibrina como arcabouço para células tronco mesenquimais associados ao fosfato de cálcio e aplicados em defeito crítico de fêmures de ratos". Universidade Estadual Paulista (UNESP), 2018. http://hdl.handle.net/11449/153174.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O reparo do tecido ósseo é um desafio antigo da ciência mundial. A partir das décadas de 70-80, os biomateriais passaram a ser explorados e hoje desempenham importante papel na engenharia tecidual. Estes, quando aplicados na enxertia óssea, devem ser bioativos, biocompatíveis e reabsorvíveis. A integração entre os diversos materiais de origem sintética e os arcabouços biológicos possui amplo espectro de uso. Dentre os arcabouços destacam-se os compostos à base de fibrina por suas propriedades hemostáticas, estabilidade e morfologia favorável à proliferação celular. A presente revisão abordou a estrutura e constituição do tecido ósseo e suas limitações no processo de reparo, a relevância da engenharia tecidual aplicada à esta finalidade e os biomateriais utilizados para otimizar tal processo, com ênfase especial aos materiais compostos por fosfatos de cálcio, células tronco mesenquimais e sua aplicação junto ao arcabouço biológico selante de fibrina, com destaque para o selante heterólogo de fibrina, agora denominado biopolímero de fibrina, um produto único e em fase de testes em experimentação animal e estudos clínicos. Propõe-se, ao final desta, uma nova abordagem para a regeneração de defeitos ósseos de ratos baseada na associação entre o selante heterólogo de fibrina, o fosfato de cálcio bifásico e células tronco mesenquimais.
Bone tissue repair is an ancient challenge of world science. From the 70s and 80s, biomaterials began to be explored and nowadays play an important role in tissue engineering. These, when applied in bone grafting, have to be bioactive, biocompatible and resorbable. The integration between the various materials of synthetic origin and biological scaffolds has a wide spectrum of use. Among these scaffolds, fibrin-based compounds are distinguished by their hemostatic properties, stability and morphology favorable to cell proliferation. The present review addressed the structure and constitution of bone tissue and its limitations in the repair process, the relevance of tissue engineering approaches applied to this purpose and the biomaterials used to optimize this process, with special emphasis on materials composed of calcium phosphates, mesenchymal stem cells and its application with the biological sealant fibrin scaffold, highlighting the heterologous fibrin sealant, now named as fibrin biopolymer, a unique product testing in animal experimentation and clinical studies. At the end of this, a new approach is proposed for the regeneration of rat bone defects based on the association between heterologous fibrin sealant, biphasic calcium phosphate and mesenchymal stem cells.

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Leite, Fábio Renato Manzolli [UNESP]. "Efeito do condicionamento radicular com ácido cítrico, citrato de sódio, EDTA e tetraciclina na adesão de elementos sanguíneos. Estudo por meio de microscopia eletrônica de varredura. -". Universidade Estadual Paulista (UNESP), 2006. http://hdl.handle.net/11449/96205.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Universidade Estadual Paulista (UNESP)
A raspagem gera smear layer que contém microrganismos e toxinas, podendo interferir no reparo periodontal. Por esse motivo, diferentes substâncias têm sido empregadas para remover esta camada e expor fibras colágenas da superfície dental. A adesão de elementos sangüíneos a superfícies radiculares desmineralizadas e a estabilização do colágeno pelas fibras colágenas são de extrema importância no sucesso da cirurgia periodontal. O objetivo deste estudo foi avaliar os diferentes padrões de adsorção e adesão de elementos sangüíneos a superfícies radiculares quimicamente condicionadas. Setenta e cinco dentes foram raspados, eqüitativamente divididos em 5 grupos: irrigação com água destilada (controle), aplicação de solução de ácido cítrico a 25%, solução de citrato de sódio a 30%, gel de EDTA a 24% e solução de cloridrato de tetraciclina a 50 mg/mL. Metade da superfície condicionada foi exposta a sangue fresco e preparada para microscopia eletrônica de varredura. As superfícies radiculares raspadas e condicionadas com EDTA e ácido cítrico apresentaram os melhores resultados em relação ao grupo controle. O ácido cítrico também se mostrou mais efetivo na remoção de smear layer e na adesão de elementos sangüíneos do que o cloridrato de tetraciclina e o citrato de sódio. Além disso, a relação entre exposição de fibras colágenas e adesão de elementos sangüíneos foi positiva. Dessa forma, o emprego de EDTA e ácido cítrico sobre a superfície radicular aumentam a adsorção e adesão de células sangüíneas e a estabilização da rede de fibrina.
Root scaling generates a smear layer which contains microorganisms and toxins that could interfere in periodontal healing. For this reason, different substances have been used to remove it and to expose collagen fibers from tooth surface. Blood elements adhesion to demineralized roots and clot stabilization by collagen fibers are extremely important for the success of periodontal surgery. The aim of this study was to evaluate the different patterns of blood elements adsorption and adhesion to root surfaces chemically conditioned. Seventy five teeth were planed and equitably divided into five groups: irrigation with distilled water (control), application of a 25% citric acid solution, 30% sodium citrate solution, 24% EDTA gel and 50 mg/mL tetracycline hydrochloride. Half of the conditioned surface was exposed to fresh blood and prepared for scanning electron microscopy. Planed root surfaces and conditioned with EDTA and citric acid showed better results when compared to control group. Citric acid was more effective on smear layer removal and blood elements adhesion to root surface than tetracycline and sodium citrate. Also, the relationship between collagen fibers exposure and blood elements adhesion was positive. This way, EDTA and citric acid employment on root surface improve blood element adsorption and adhesion to root surface and fibrin network stabilization.

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Jordán, Sales Marcos. "Prevención del sangrado postoperatorio en fracturas subcapitales de fémur tratadas mediante sustitución protésica: eficacia y seguridad del ácido tranexámico y la cola de fibrina". Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/457640.

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Objetivos: El objetivo principal del estudio fue evaluar la eficacia y la seguridad del ácido tranexámico y de la cola de fibrina administrados vía tópica en pacientes intervenidos de fractura subcapital de fémur mediante artroplastia de cadera. Material y métodos: Se realizó un estudio prospectivo, aleatorizado, multicéntrico y paralelo en pacientes con fractura de cadera que precisaron sustitución protésica, comparando tres grupos: un grupo control en el que sólo se realizó hemostasia habitual, un grupo de recibió 1g de ácido tranexámico (ATX) (Amchafibrin®) tópico al final de la cirugía y otro grupo que recibió 10 ml de cola de fibrina (CF) comercializada (Evicel), igualmente tópica al final de la cirugía. Se estudió como variable principal la pérdida sanguínea recogida en los redones y como variables secundarias la sangre total perdida calculada por la fórmula de Nadler, la sangre oculta perdida, las transfusiones realizadas y el número de concentrados de hematíes utilizados, la estancia media hospitalaria, las complicaciones, los eventos adversos y la mortalidad. Resultados: Se incluyeron un total de 158 pacientes, 50 en el grupo control, 52 en el grupo con ATX y 56 en el grupo con CF. En el análisis por intención de tratar, el sangrado total recogido por los redones, la sangre total perdida y la sangre oculta perdida fue menor en el grupo de ATX sin significación estadística respecto a los otros grupos (p=0,178, p=0,063 y p=0,321 respectivamente). En el análisis por protocolo, los resultados fueron similares excepto que en el grupo de ATX la sangre total perdida fue menor de forma significativa (p=0.048), comparativamente con los otros grupos. Respecto a la tasa transfusional, en el grupo de ATX el 33% de los pacientes necesitó transfusión, frente al 43% de los pacientes del grupo de CF y un 44% del grupo control (p=0,431). No existieron complicaciones ni afectos adversos relacionados con las intervenciones evaluadas. Conclusiones: La utilización del ATX ( 1g) y de la CF (10 ml) administrados de forma tópica antes del cierre quirúrgico en los pacientes con una fractura subcapital de fémur intervenidos con artroplastia de cadera no redujo significativamente ni la pérdida sanguínea postoperatoria por los redones ni la tasa transfusional, comparados con un grupo similar en que sólo se realizó hemostasia habitual. La cola de fibrina y el ácido tranexámico tópico a las dosis utilizadas fueron tratamientos seguros.
Objectives: The main objective of the study was to evaluate the efficacy and safety of tranexamic acid and fibrin sealant administered topically in patients with a femoral neck fracture operated with a hip arthroplasty. Material and methods: A prospective, randomized, multicentric and parallel study was performed in patients with hip fracture requiring prosthetic replacement. We compared three groups: a control group with only usual hemostasis, a group that received 1 g of topical tranexamic acid (TXA) (Amchafibrin®) at the end of the surgery and a group that received 10 ml of topical fibrin sealant (FS) (Evicel®) at the end of the surgery. Blood loss collected in the blood drains was studied as the main variable and were also analyzed other secondary variables such us: the total blood loss calculated by the Nadler´s formula, the hidden blood loss, the transfusions performed and the number of hemoglobin concentrates used, the average hospital stay, complications, adverse events and mortality. Results: A total of 158 patients were included, 50 in the control group, 52 in the TXA group and 56 in the FS group. In the intention-to-treat analysis, the total bleeding collected by the drains, the total lost blood and the hidden blood loss was lower in the TXA group without statistical significance in relation with the other groups (p=0.178, p=0.063 and p=0.321 respectively). In the protocol analysis, the results were similar except that the group of TXA showed significantly lower total blood loss compared with the other groups (p=0.048). Regarding the transfusion rate, 33% of the patients needed transfusion in the TXA group, compared to 43% in the FS group and 44% in the control group (p=0.431). There were no complications or adverse affects related to the evaluated interventions. Conclusions: The use of TXA (1 g) and FS (10 ml) administered topically prior to surgical closure in patients with a femoral neck fracture operated with hip arthroplasty did not significantly reduce either postoperative blood loss or the transfusion rate compared with a similar group in which only received usual hemostasis. Fibrin sealant and topical tranexamic acid, at the doses used, were safe treatments.

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Bense, Christine Adelle. "The in vitro stability of cross-linked fibrin and fibrin/hyaluronan-coated polyurethanes in the presence of plasmin". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0012/MQ40903.pdf.

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NORTH, CHARLES. "Les maladies associees a une fibrinemie superieure a 10 g/l chez l'adulte : a propos de 180 cas". Besançon, 1994. http://www.theses.fr/1994BESA3002.

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De, Giorgio-Miller Alexander Michael. "The role of fibrin in skin fibrosis". Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397228.

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English, Elizabeth J. "Micropatterned Fibrin Hydrogels for Increased Cardiomyocyte Alignment". Digital WPI, 2019. https://digitalcommons.wpi.edu/etd-theses/1347.

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Cardiovascular disease is the leading cause of death in the US, which can result in blockage of a coronary artery, triggering a myocardial infarction (MI). After a MI, hypoxic ventricular myocardial tissue dies, resulting in the deposition of non-contractile scar tissue and remodeling of the ventricle, leading to decreased cardiac output and ultimately heart failure. Currently, the gold-standard solution for total heart failure is a heart transplant. As donor hearts are in short supply, an alternative to total-organ transplantation is surgically remodeling the ventricle with the implantation of a cardiac patch. Acellular cardiac patches have previously been investigated using synthetic or decellularized native materials in effort to improve cardiac function. However, a limitation of this strategy is that acellular cardiac patches only reshape the ventricle and do not increase cardiac contractile function. By incorporating the use of a clinically relevant cell type and by matching native architecture, we propose the use of a highly aligned fibrin scaffold to support the maturation of human induced pluripotent stem cell cardiomyocytes (hiPS-CM) for use as a cell-populated cardiac patch. By micropatterning fibrin hydrogels, hiPS-CM seeded on the surface of this scaffold become highly aligned, which is crucial for increased contractile output. Our lab previously developed a composite fibrin hydrogel and microthread cardiac patch matching mechanical properties of native myocardium. By micropatterning fibrin hydrogel alone, we were able to match cellular alignment of hiPS-CM to that of native myocardium. hiPS-CMs seeded on this surface were found to express distinct sarcomere alignment and circumferential connexin-43 staining at 14 days of culture as well as cellular elongation, which are necessary for mature contractile properties. Constructs were also cultured under electrical stimulation to promote increased contractile properties. After 7 days of stimulation, contractile strains of micropatterned constructs were significantly higher than unpatterned controls. These results suggest that the use of topographical cues on fibrin scaffolds may be a promising strategy for creating engineered myocardial tissue to repair damaged myocardium.

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Senderoff, Richard I. "Development of fibrin-based drug delivery systems /". The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487677267728699.

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Davies, Thomas Marc. "Microstructure and mechanical properties of fibrin gels". Thesis, Swansea University, 2009. https://cronfa.swan.ac.uk/Record/cronfa42760.

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This thesis reports an extensive study of the structural and rheological characteristics of the three-dimensional fibrin clot network. The importance of blood clotting in the area of NanoHealth is testified to by the fact that complications due to thrombosis accounts for about 10 per cent of all deaths in hospitals in the UK. It is therefore imperative to understand the clotting process of blood as fully as possible. The techniques implemented include confocal laser scanning microscopy, and rheo logical methods such as Fourier transform mechanical spectroscopy. Both techniques provide a foundation for performing a fractal analysis as a quantitative basis for defining, where appropriate, morphological/micro structural differentiation in clotting. Fractal analysis provides the framework for structural complexity and allows us to develop relationships between the structural features of blood clots and their rheological properties. The experimental methods involve following the mechanical properties of a gelling system up to and beyond the gel point. The mechanical (viscoelastic) properties of fibrin are significant and unique among polymers. Hence, they are essential to the physiology of blood clotting and vital for the understanding and therefore prevention and treatment of thrombosis. An unsatisfactory aspect of work in this area is that the micro structures of such clots are usually reported in only adjectival terms (e.g., "dense" or "tight") - usually on the basis of a visual inspection of fragments of desiccated clots in SEM micrographs. This work includes an extensive approach using confocal microscopy to visualise fibrin clot networks, with several forms of fractal analysis investigated for quantifying structural complexity. The present study is the first to report a modification of the fractal characteristics of incipient clots in fibrin-thrombin gels due to the availability of thrombin. This work confirms the hypothesis that the self-similar (fractal) stress relaxation behaviour recorded at the Gel Point of samples of coagulating blood (Evans et al., 2008) is associated with the micro structural characteristics of the incipient blood clot's fibrin network. It also supports the hypothesis that in various pathologies prothrombotic conditions can modify the underlying micro structure of a blood clot. The provision of a new technique capable of detecting the formation of altered clot microstructures at their incipient state could have significant clinical diagnostic potential e.g. in thromboembolic disease screening applications.

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Bänninger, Hans Bänninger Hans. "Binding of alpha-thrombin to fibrin depends on the quality of the fibrin network : und ; Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V /". [S.l.] : [s.n.], 1996. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

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Nakamuta, Juliana Sanajotti. "Terapia celular para isquemia cardíaca: efeitos da via de administração, do tempo pós-lesão e do uso biopolímero para a retenção das células e função miocárdica". Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-09062009-110321/.

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A terapia celular representa uma abordagem promissora para o tratamento de cardiopatia isquêmica, porém aspectos-chave dessa estratégia permanecem incertos. Neste trabalho avaliamos a eficiência da retenção cardíaca de células da medula óssea marcadas com tecnécio (99m Tc-CMO) transplantadas, de acordo com o tempo após o infarto (1, 2, 3 e 7 dias) e a via de administração dessas células (intravenosa [IV], intraventricular [IC], intracoronariana [ICO] e intramiocárdica [IM]), em ratos submetidos à isquemia-reperfusão cardíaca [I&R]. Após 24 horas, a retenção cardíaca de 99m Tc-CMO foi maior na via IM comparada com a média alcançada pelas demais (6,79% do total injetado vs. 0,53%). O uso de fibrina como veículo para a injeção de células incrementou a retenção em 2.5 vezes (17,12 vs. 6,84%) na via IM. Curiosamente, quando administradas após 7 dias, a retenção de células na via IM alcançou valores próximos dos observados com da matriz de fibrina injetadas 24 h após a I&R (16,55 vs. 17,12%), enquanto que para as demais vias as mudanças foram insignificantes. Nos animais em que as CMO foram administradas por via intramiocárdica 24 horas após a I&R, com ou sem fibrina, observou-se melhora significante do desempenho cardíaco frente ao estresse farmacológico com fenilefrina quando comparados aos controles. Em conjunto, os dados mostram a biodistribuição das células injetadas após a I&R por 4 diferentes vias e 4 intervalos de tempo pós-lesão e indicam que a via IM é a que produz maior retenção cardíaca. O uso do biopolímero de fibrina aumenta a retenção das células e a eficácia deste efeito sobre a função cardíaca e mortalidade dos animais em longo prazo, além de 30 dias pós I&R, merecerá ser investigada no futuro.
Cell therapy represents a promising approach for ischemic cardiac disease, but key aspects of this strategy remain unclear. We examined the effects of timing and route of administration of bone marrow cells (BMCs) after myocardial ischemia/reperfusion injury (I&R). 99mTc-labeled BMCs were injected by 4 different routes: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV+) and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days after infarction. Cardiac retention was higher following the IM route compared to the average values obtained by all other routes (6.79% of the total radioactivity injected vs. 0.53%). Use of a fibrin biopolymer as vehicle during IM injection led to a 2.5-fold increase in cardiac cell accumulation (17.12 vs. 6.84%). Interestingly, the retention of cells administered with culture medium at day 7 post-MI by the IM route was similar to that observed when cells were injected 24 h post-IM using fibrin (16.55 vs 17.12%), whereas no significant changes were observed for the other routes. Cell therapy 24 hs post MI by IM injection, with or without fibrin, resulted in comparable improvement in cardiac function under pharmacological stress compared to control animals. Together, we provide evidence for the biodistribution of 99mTc-labeled BMCs injected post MI by 4 different routes and times post-injury, which shows that the IM rout is the most effective for cardiac cell retention. The use of a fibrin biopolymer further increased cardiac cell retention and its potential long term benefits, beyond 30, on reducing mortality and improving cardiac function deserve to be explored in the future.

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Scapini, Fabricio. "Efeito da cola de fibrina na deposição de colágeno após enxertia autóloga da fáscia em pregas vocais de coelhos: estudo histomorfométrico". Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-25112010-152624/.

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A incompetência glótica ainda representa um desafio para a laringologia. Implantes de biomateriais no espaço de Reinke ou no espaço paraglótico estão entre as opções de tratamento, e suturas e confecção de bolsões subepiteliais são normalmente utilizados para fixação desses implantes. Alternativamente, a cola biológica pode ser usada como adesivo nesses casos. A cola de fibrina (CF) é produto da reação de dois componentes do sistema de coagulação: o fibrinogênio e a trombina, que formam uma rede de fibrina, responsável, entre outros, pela adesão dos tecidos. Entretanto, além do efeito adesivo, a CF e seus componentes podem interferir no processo cicatricial, atuando sobre citocinas como o fator de crescimento transformador-beta (TGF-beta). O objetivo deste estudo é avaliar o efeito da cola de fibrina na deposição de colágeno após enxertia de fáscia em pregas vocais de coelhos. Dezoito coelhos foram submetidos a enxerto de fáscia em ambas as pregas vocais, sendo o lado esquerdo fixado com CF. Os coelhos foram sacrificados após 7, 30 e 90 dias. As laringes foram removidas e as pregas vocais preparadas para estudo histomorfométrico através da coloração picrossirius, a fim de avaliar a deposição de colágeno total em torno do enxerto. Foi observado um aumento estatisticamente significativo na densidade de colágeno em torno dos enxertos de fáscia nas pregas vocais que receberam a CF (p=0,0102) após 90 dias, em comparação com as pregas vocais controles. A aplicação da CF interferiu na deposição de colágeno em torno dos enxertos de fáscia, resultando em um aumento significativo na densidade de colágeno após 90 dias, possivelmente em decorrência da interação de seus componentes com citocinas e células envolvidas no processo de cicatrização
The glottal incompetence is still a challenge in Laryngology. Implants of biomaterials in Reinkes space or paraglottic space are among the treatment options, and sutures and pockets dissections are usually used to set these implants. Alternatively, biological glue can be used as adhesive in these cases. Fibrin glue (FG) is the product reaction of two components of the coagulation system: the fibrinogen and thrombin that form a fibrin net, responsible for the tissues adhesion, among other functions. However, the FG and its components may interfere in wound healing, interacting with cytokines as the transforming growth factor-beta (TGF-beta). The objective is to study the effect of fibrin glue on collagen deposition after fascia grafting on the rabbits vocal folds. Eighteen rabbits were submitted to the fascia graft on both vocal folds, being the left side fixed with FG. The rabbits were sacrificed after 7, 30 and 90 days. The larynx were removed and vocal folds prepared for histomorphometric study through Picrosirius Red stain, in order to evaluate the collagen deposition around the graft. There was a significant increase in collagen density around the grafts on the vocal folds that received FG (p=0.0102) after 90 days, compared with the control. FG application interfered in collagen deposition around fascia grafts, resulting in a significantly increase of collagen density after 90 days, which possibly resulted from the interaction of FG and its components with the cytokines and cells involved in the wound healing

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Rojas, Jose Eduardo Ulloa. "Preparation and characterization of fibroin hydrogels for potential application in photodynamic therapy". reponame:Repositório Institucional da UFABC, 2017.

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Orientador: Prof. Dr. Wendel Andrade Alves
Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, 2017.
A pesquisa em materiais naturais aumentou notavelmente nos últimos anos devido à oportunidade de combinar biocompatibilidade com propriedades físicas, mecânicas e químicas excepcionais, o que seria árduo para obter seguindo uma rota sintética. Entre estes polímeros naturais, a fibroína de seda é atraente por sua transparência óptica, excelente robustez mecânica e compatibilidade com sistemas vivos, com a formação de produtos de degradação não inflamatória. Neste estudo, fomos capazes de formar hidrogéis translucidos a partir de fibras de seda crua em diferentes concentrações e usamos como matriz para incorporar uma molécula fotossensível : sódio (4,4 ', 4' '- (20- (4- (3-carboxipropanamido ) Fenil) porfirina-5,10,15-triil) tribenzenossulfonato - para uso futuro na terapia fotodinâmica. Os hidrogéis obtidos foram caracterizados por diferentes técnicas de reologia e análise de espectrofotometria para estudar os fatores envolvidos na formação do hidrogel e para obter informações sobre propriedades da fibroína da seda (SF) após a adição da molécula de porfirina na matriz. O conjunto de resultados obtidos mostrou que os hidrogéis SF têm um comportamento de desbaste de cisalhamento, onde a viscosidade do gel diminui com o aumento da taxa de cisalhamento e que pode ser classificado como materiais tixotrópicos, o que significa que a estrutura do material precisa de tempo para se recuperar após a deformação de cisalhamento da experiência. Além disso, observamos que a estrutura secundária da fibroína não é afetado pela adição de porfirina em qualquer concentração, foi confirmado pelo sinal negativo de Cotom em torno de 220 nm nos espectros de dicroísmo circular. As nanofibras de fibroína porfirina híbridas foram capazes de gerar oxigênio singlete após a gelificação, e provamos que os hidrogéis de fibroína de seda são uma excelente matriz para encapsular outras moléculas para aplicação em terapia fotodinâmica e terapia fototérmica, levando à formação de nanoestruturas de péptido auto-montadas com efeitos fototerapêuticos controláveis.
The research in to natural materials has notably increased in recent years due to the opportunity of combining biocompatibility with exceptional physical, mechanical, and chemical properties, which would be arduous to obtain following a synthetic route. Among these natural polymers, silk fibroin is attractive because of its optical transparency, outstanding mechanical robustness and compatibility with living systems, with the formation of non-inflammatory degradation products. In this study, we were capable to form translucid hydrogels from raw silk fibers at different concentrations and used them as matrix to incorporate a photosensitive molecule - sodium (4,4',4''-(20-(4-(3- carboxypropanamido) phenyl) porphyrin-5,10,15-triyl) tribenzenesulfonate - for future use in photodynamic therapy. The obtained hydrogels were characterized by different rheology techniques and spectrophotometry analysis to study the factors that are involved in the formation of the hydrogel, and to have information about silk fibroin (SF) properties after adding the porphyrin molecule to the matrix. The set of obtained results showed that the SF hydrogels have a shear thinning behavior, where the viscosity of the gel decrease whit the increase of the shear rate, and that it can be classified as thixotropic materials. This mean that the structure of the material needs time to recover after experience shear deformation. Also, we observed that the secondary structure of the fibroin is not affected by the addition of porphyrin in any concentration, it was confirmed by the negative Cotton signal around 220 nm in the circular dichroism spectra. The hybrid porphyrin-fibroin nanofibers were capable to generate singlet oxygen after gelification, and we proved that silk fibroin hydrogels are an excellent matrix to encapsulate other molecules to application in photodynamic therapy and photothermal therapy, leading to the formation of selfassembled peptide nanostructures with controllable phototherapeutic effects.

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Edgell, Tracey Ann. "An investigation of fibrin formation using specific monoclonal antibodies, and the development of an assay to detect soluble fibrin". Thesis, University of Hertfordshire, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323431.

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47

Seyve, Landry. "Analyse de la structure du caillot en conditions physiologiques et pathologiques". Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAS027.

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Physiologiquement, le caillot sanguin a pour fonction l’arrêt d’un saignement consécutif à une brèche vasculaire. Dans un premier temps, ce sont les plaquettes sanguines qui stoppent l’épanchement sanguin, rapidement soutenues par la formation d’un réseau de fibres de fibrine qui consolide et confère au caillot les propriétés nécessaires pour résister à la pression sanguine et à la fibrinolyse. Le fibrinogène est l’élément de base du réseau de fibrine. Lors d’une brèche vasculaire, la libération de facteur tissulaire entraine le déclenchement de la cascade de coagulation qui aboutit à la transformation du fibrinogène en monomères de fibrine par l’action de la thrombine. Ceux-ci s’agrègent longitudinalement pour former des protofibrilles, puis latéralement pour former un réseau de fibres de fibrine.A ce jour, de nombreuses étapes de formation du caillot ont été décrites en détail dans la littérature, cependant les mécanismes et les forces motrices de l’agrégation latérale des protofibrilles sont encore mal compris.Lors de ce travail, nous avons étudié différents profils de coagulation : de l’hypo-coagulant à l’hypercoagulant, en passant par le profil normal et en utilisant un panel varié de techniques : génération de thrombine, génération de plasmine, Fibrinographie, Fibrinographie en mode « fibrinolyse », microscopie confocale, thromboélastométrie et diffraction des rayons X aux petits angles.Nous avons mis en évidence la relation entre la quantité de thrombine présente lors de la formation d’un caillot et la structure de celui-ci. En effet, Plus il y a de thrombine, plus le nombre de protofibrilles par fibre est faible et plus le nombre de fibres est important. De plus, nous avons corrélé le temps d’initiation de l’agrégation latérale des fibres en Fibrinographie avec l’initiation de la génération de plasmine. Nous avons ainsi mis en évidence la production d’une structure du caillot de fibrine anormale en présence de dabigatran, grâce à l’utilisation combinée de la microscopie confocale et de la Fibrinographie.Cette analyse multimodale de la structure du caillot dans différentes conditions apporte des informations supplémentaires à la communauté scientifique, pour permettre de mieux comprendre les mécanismes de formation des caillots de fibrine
Physiologically, the blood function of the clot is to stop bleeding following a vascular breach. Initially, platelets stop blood flow, quickly supported by the formation of a fibrin fibers network that strengthens and gives properties to resist the blood pressure and fibrinolysis. Fibrinogen is the basic element of the fibrin network. During a vascular breach, the release of tissue factor triggers the coagulation cascade that results in the conversion of fibrinogen to fibrin monomers by the action of thrombin. These aggregate longitudinally to form protofibrils, then laterally to form a network of fibrin fibers.To date, many stages of the clot formation have been described in detail in the literature, however the mechanisms and driving forces of the lateral aggregation of protofibrils are still poorly understood.During this work, we studied different coagulation profiles: from hypo-coagulant to hyper-coagulant, through the normal profile and using a varied range of techniques: thrombin generation, plasmin generation, Fibrinography, Fibrinography in "fibrinolysis" mode, confocal microscopy, thromboelastometry and X-ray diffraction at small angles.We have highlighted the relationship between the amount of thrombin present during clot formation and the clot structure. Indeed, the more thrombin there is, the lower the protofibrils number per fiber and the greater the number of fibers. In addition, we correlated the initiation time of lateral fibers aggregation in Fibrinography with the initiation of plasmin generation. We have thus demonstrated the production of an abnormal fibrin clot structure in the presence of dabigatran, thanks to the combined use of confocal microscopy and Fibrinography.This multimodal analysis of the clot structure under different conditions provides additional information to the scientific community to better understand the mechanisms of fibrin clot formation

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48

Rao, Shiva Priya. "Amyloid Fibrils in Bionanomaterials". Thesis, University of Canterbury. Biological Sciences, 2008. http://hdl.handle.net/10092/4415.

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Amyloid fibrils are a type of protein nanofibres that form when a normally soluble protein aggregates in a regular fashion via self-association. Their organised and repetitive β-sheet structure is thought to be a generic property of all proteins, depending on the environmental conditions. The nanometre size and high stability of these protein nanofibres are attractive features to exploit in bionanomaterials. This thesis aimed to manipulate insulin amyloid fibrils, as a model protein nanofibre system, through investigating the effect of chemical modification on insulin fibril formation in heterogeneous mixtures. Using acetylation, reduction carboxymethylation, reduction pyridylethylation, trypsin digestion and chymotrypsin digestion, it was shown that nanofibres can form in heterogeneous mixtures of modified insulin at variable rates to produce fibrils of distinct morphologies. Distinctively well defined, long, unbranched nanofibres were observed in the crude reduced carboxymethylated insulin mixture after incubation at 60°C (pH 7.4), which formed at a faster rate than native insulin. The crude reduced pyridylethylated insulin revealed the formation of “wavy” fibrils when exposed to 60°C and pH 1.6, compared to the straight native insulin amyloid fibrils. Although, the trypsin digestion inhibited nanofibre formation at 60°C and pH 1.6, chymotrypsin digestion of insulin produced a mixture of long and short nanofibres under the same conditons. Thus chemical modification provides a simple means of manipulating protein nanofibre assembly for use in bionanotechnology. Protein nanofibres were incorporated into a model polymer polyvinylalcohol (PVOH) film in order to assess the impact on material properties. A systematic study involving both insulin and a crude source of crystallin proteins derived from bovine eye lens was undertaken. A protein nanofibre-PVOH nanocomposite was successfully fabricated by a procedure of solution mixing and casting. Dynamic mechanical analysis showed that the addition of insulin fibrils did not change the stiffness of the PVOH. However, an increase in the stiffness of the PVOH-crude bovine eye lens composites was found. Both insulin and bovine eye lens nanofibres reduced the damping properties of the polymer, which suggested a reduction in molecular mobility/slipping. The results revealed that protein nanofibre formation can be controlled through the modification of the protein and that nanofibres may alter polymer properties in a protein specific manner. Employing these findings in the development of novel bionanomaterials that use the protein nanofibres as a form of natural scaffolding offers a fruitful avenue of future research.

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Pan, Xiaoxi. "Fibrin clot structure alterations after particulate matter exposure". Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/14310/.

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Particulate matter (PM) as an important part of ambient air pollution has been associated with increased risks of cardiovascular diseases. Fibrin clot structure alteration is an emerging risk factor of many cardiovascular diseases, especially thrombosis. Therefore, the aim of this study was to investigate whether and how air particulate matter affects fibrin clot structure and endothelial cell behaviour. Turbidity assay, turbidity lysis assay and laser scanning confocal microscopy were used to analyse clots formed from normal pooled plasma or purified fibrinogen, in the presence of varying concentrations of PM. It was found that clots formed from plasma with higher concentrations of particles led to prolonged lysis time compared to control. No differences were seen for clots formed from fibrinogen. In a study of clots formed from plasma samples collected as part of a previous study on the effects of air pollution on deep vein thrombosis (DVT), alterations were observed in clots formed from plasma of DVT patients exposed to high levels of PM compared to those exposed to low levels, but the same differences were not observed in clots formed from plasma of control subjects. To investigate the potential role of venous endothelial cells in moderating clot structure following exposure to PM, human umbilical vein endothelial cells (HUVEC) were treated with PM for 24 hours and clots subsequently formed on the cells. Clots formed from plasma on the treated cells were altered compared to controls. RT-PCR and ELISA results showed increased gene expression of tissue factor (TF), protein expression of von Willebrand Factor (VWF) and plasminogen activation inhibitor-1 (PAI-1) and decreased thrombomodulin mRNA expression which were consistent with changes observed in clot structure. Engineered SiO2 nanoparticles caused denser clot structure in clots formed from normal pooled plasma. The gene expression of thrombomodulin was inhibited by SiO2 nanoparticles, but there were no significant difference in the TF mRNA expression between control and treated cells. Silica NPs caused increased concentrations of VWF, but not PAI-1 produced by endothelial cells. The results presented here show that PM can induce changes to clot structure and function, and that changes in gene expression induced in endothelial cells may be a mechanism by which a prothrombotic state is induced in response to PM exposure. Furthermore, some, but not all, similar changes were observed in clots and cells exposed to SiO2 nanoparticles, raising the possibility that such engineered nanoparticles may also have the potential to contribute to cardiovascular toxicity.

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50

Geer, Carri Brodnax Lord Susan T. "Analytical studies on the mechanism of fibrin formation". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1458.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.
Title from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry with Emphasis in Biophysics." Discipline: Chemistry; Department/School: Chemistry.

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