Mesenchymal stem cells (MSCs) may benefit vascular cell-based therapies as smooth muscle or endothelial cell substitutes or through paracrine actions to repair, replace, or regenerate vascular tissue. Previous studies have demonstrated that MSCs can adopt traits of smooth muscle cells (SMCs) or endothelial cells (ECs), as well as secrete specific factors that tune signaling and material properties in the local environment. Few studies have investigated the cell signaling response of MSCs to mechanical forces present in the vasculature: specifically, shear stress due to blood flow and cyclic strain due to pulsatile blood flow. Thus, the central objective of this dissertation was to determine the signaling responses of MSCs to vascular-relevant applied physical forces, in comparison with that of differentiated vascular cells. Vascular-relevant mechanosignaling of MSCs was assessed through two comparisons: (1) MSC and SMC responses to applied cyclic strain and (2) MSC and EC responses to applied fluid shear stress. MSCs and SMCs were seeded on fibronectin-coated silicone and subjected in vitro to cyclic strain (10%, 1 Hz) or parallel static culture using a custom-built equibiaxial cyclic strain device. Gene expression analysis of 84 signal transduction molecules demonstrated both cell types respond with significant (p<0.05, n=3) fold-changes (|FC|≥ 1.5) within 24 hours of applied equibiaxial strain. Most strain-responsive genes identified were significantly strain-responsive in only one cell type. A signaling trio of Interleukin 8, Vascular cell adhesion molecule 1, and Heme oxygenase 1 was significantly altered in both MSCs and SMCs, suggesting cyclic strain regulates immune and inflammatory functions in both cell types. The response to shear stress of MSCs and ECs was compared using cells seeded on type I collagen or fibronectin and exposed to steady laminar shear stress (5 or 15 dyn/sq-cm) using a parallel plate shear chamber system. Gene expression was compared in MSCs and ECs for a panel of immune and inflammation-related markers. Expression of Cox-2 and Hmox-1 increased significantly (p<0.05, n≥3; |FC|≥1:5) in both cell types. Reduced shear stress-responses of Mcp-1, Pecam-1, and VE-Cad in MSCs relative to ECs suggests that MSCs promote less inflammation and immune activation in response to shear stress than ECs. Mechanosensitivity profiles for MSCs and differentiated vascular cells were broadened using whole genome microarrays. These high-throughput studies confirmed that (1) signaling profiles between sample groups vary significantly more (p<0.05, n=3) with cell type than applied force condition and (2) a subset of conserved mechanosensitive genes alter expression levels significantly and in the same direction fold-change in multiple cell types. Bioinformatics analysis of these conserved mechanoresponsive genes highlighted oxidative stress, cell cycle, and DNA replication as functions regulated by vascular-relevant mechanical cues. These studies demonstrate that MSCs partially reproduce differentiated vascular cell mechanosignaling, while simultaneously altering expression of genes not typically force-responsive in vascular cells. This work defines a role for conserved mechanosignals, based on genes whose expression in response to applied force alters significantly (p<0.05, n≥3) and by at least 1.5-fold change in multiple cell types and/or force types. Comparisons completed for this dissertation motivate future studies to track the functional impact of specific similar or unique MSC mechanoresponses. This work contributes to design of MSC-based vascular therapies and an understanding of stem and differentiated cell mechanobiology.

Grandes perdas de tecido neural não permitem a reparação por meio de anastomose primária. Nesses casos, a auto-enxertia de nervo é considerado o melhor tratamento. A despeito de um tratamento cirúrgico adequado, déficits funcionais são observados e melhoras quanto à recuperação funcional e diminuição das seqüelas são desejáveis. Várias são as técnicas que almejaram esse propósito. A interposição de condutores tubulares, como ponte entre os cotos proximal e distal do nervo seccionado, apresenta-se como uma técnica alternativa que oferece vantagens teóricas. A veia é um material estudado como possível condutor tubular avaliado experimentalmente e em casos clínicos. Estudos recentes têm dado importância na utilização de transplantes de tecidos armazenados em banco de tecidos. O glicerol é utilizado para preservação de tecidos, tendo sido relatado seu uso em nervos e vasos. Entretanto, não há relatos da utilização de veias preservadas em glicerol como substituto de enxerto de nervo. O objetivo deste trabalho foi comparar, em ratos, o grau de regeneração neural, utilizando análise histológica e análise funcional, obtida com a interposição de enxerto autógeno de nervo, veia autógena, veia autógena preservada em glicerol e veia alógena preservada em glicerol. Com técnica microcirúrgica, foram criados defeitos de 5 mm do nervo fibular de ratos da raça Lewis. Os animais foram divididos em quatro grupos de seis, de acordo com o tratamento empregado para correção do defeito: nos animais do Grupo A (grupo controle), foi realizado o reposicionamento do fragmento de nervo retirado (auto-enxerto); nos animais do Grupo B, foi interposto um segmento de 1 cm de veia jugular externa autógena; nos animais do Grupo C, foi interposto a veia jugular externa autógena preservada em glicerol a 98% a 4ºC por sete dias; no Grupo D os animais doadores foram ratos da raça Sprague-Dawley que tiveram a veia jugular externa preservada em glicerol de forma igual ao Grupo C e utilizadas para reconstrução do defeito neural em ratos da raça Lewis, sendo considerado um enxerto alógeno preservado em glicerol. Os animais foram sacrificados após seis semanas para realização dos estudos histológicos. Para a avaliação da recuperação funcional foram estudados os padrões de deambulação dos ratos (\"walking track analysis\") no pós-operatório imediato, 3 e 6 semanas de pós-operatório. O grupo controle (auto-enxerto) apresentou resultados histológicos semelhantes aos grupos de veias preservadas em glicerol (autógena e alógena), entretanto apresentou uma maior reação tecidual perineural e maior presença de escape axonal se comparada a todos os grupos. A utilização de veia autógena sem preservação demonstrou padrão histológico com maior neoangiogênese e áreas de rarefação axonal com presença de tecido conectivo no estroma neoformado. O padrão histológico foi semelhante nos demais grupos. O grupo que utilizou veia autógena (sem glicerol) apresentou menor recuperação funcional quando comparado com os demais grupos para 3 e 6 semanas. O resultado funcional foi estatisticamente semelhante entre os grupos de veias preservadas (autógena e alógena) e o auto-enxerto. / Great losses of neural tissue cannot be repaired by primary conventional suturing. In such cases, nerve autografting is considered to be the treatment of choice. In spite of adequate surgical treatment, functional deficits occur. Also, improvement in functional recuperation and decrease in sequelae are expected. There are many techniques aiming at this purpose. The interposition of tubular conduits, as a bridge between the ends of a sectioned nerve, among these the vein graft, is an alternative technique which offers theoretical advantages. The vein is a studied material as possible evaluated tubular conductor experimentally and in clinical cases. Recent studies have given importance in the use of tissues transplants stored in banks. Glycerol is used for tissue preservation, having been told to its use in nerves and vessels. However, it does not have studies of the use of glycerol reserved veins in as substitute of nerve graft. The purpose of this study was to compare, in rats, the neural regeneration degree, using histological analysis and functional analysis, obtained after interposition of a nerve graft, autogenous vein, autogenous vein preserved in glycerol and allograft vein preserved in glycerol. A 5 mm neural gap in the fibular nerve of rats (Lewis breed) has been created under microsurgical techinique. Four groups of six animals each have been divided according to the treatment employed: Group A - control group: replacement of the fibular nerve itself (autograft); Group B - a 1omm segment of external jugular vein was interposed; Group C - a preserved external jugular vein in glycerol 98% per 7 days was interposed in the fibular nerve gap; Group D - external jugular vein preserved in glycerol of Sprague-Dawley rats had been used equal form to group C in Lewis rats. The animals had been sacrificed after 6 weeks for accomplishment of the histological studies. The functional walking track analysis was performed after in the pre-op, and in the pos-op (immediately, 3 and 6 weeks). The control group (autograft) presented similar histological results to the groups of glycerol preserved veins (autogenous vein and allograft vein), however it presented a bigger perineural tecidual reaction and bigger presence of escape axonal if compared with all the groups. The use of autogenous vein without preservation demonstrated histological results with greater neoangiogenesis and presence of connective tissue inside the neo-formed stroma. Histological pattern was similar to other studied groups. The group that used autogenous vein (without glycerol) presented little functional recovery for 3 and 6 weeks. No statistical difference was seen between groups A (autograft) and groups C and C(preserved veins) in the degree of functional recovery.

A auto-enxertia de nervo é considerado o melhor tratamento para a restauração de grandes perdas de nervo periférico. Mesmo com o tratamento cirúrgico adequado, déficits funcionais são observados e melhoras quanto à recuperação funcional e diminuição das seqüelas são desejáveis. Várias são as técnicas que almejaram esse propósito. A interposição de condutores tubulares, como ponte entre os cotos proximal e distal do nervo seccionado, apresenta-se como uma técnica alternativa que oferece vantagens teóricas. A veia é um material estudado como possível condutor tubular avaliado experimentalmente e em casos clínicos. Estudos recentes têm dado importância na utilização de transplantes de tecidos armazenados em banco de tecidos. O glicerol é utilizado para preservação de tecidos, tendo sido relatado seu uso em nervos e vasos. Entretanto, não há relatos da utilização de veias preservadas em glicerol como substituto de enxerto de nervo. O objetivo deste trabalho foi comparar, em ratos, o grau de regeneração neural, utilizando análise histológica qualitativa e quantitativa e a recuperação funcional, obtida com a interposição de enxerto autógeno de nervo, veia autógena, veia autógena preservada em glicerol e veia alógena preservada em glicerol. Com técnica microcirúrgica, foram criados defeitos de 5 mm do nervo fibular de ratos da raça Lewis. Os animais foram divididos em quatro grupos de seis, de acordo com o tratamento empregado para correção do defeito: nos animais do Grupo A (grupo controle), foi realizado o reposicionamento do fragmento de nervo retirado (auto- enxerto); nos animais do Grupo B, foi interposto um segmento de 1 cm de veia jugular externa autógena; nos animais do Grupo C, foi interposto a veia jugular externa autógena preservada em glicerol a 98% a 4ºC por sete dias; no Grupo D os animais doadores foram ratos da raça Sprague-Dawley que tiveram a veia jugular externa preservada em glicerol de forma igual ao Grupo C e utilizadas para reconstrução do defeito neural em ratos da raça Lewis, sendo considerado um enxerto alógeno preservado em glicerol. Os animais foram sacrificados após seis semanas para realização dos estudos histológicos. Para a avaliação da recuperação funcional foram estudados os padrões de deambulação dos ratos (walking track analysis)no pós-operatório imediato, 3 e 6 semanas de pós-operatório. O grupo controle (auto-enxerto) apresentou resultados histológicos semelhantes aos grupos de veias preservadas em glicerol (autógena e alógena), entretanto apresentou uma maior reação tecidual perineural e maior presença de escape axonal se comparada a todos os grupos. A utilização de veia autógena sem preservação demonstrou padrão histológico com maior neoangiogênese e áreas de rarefação axonal com presença de tecido conectivo no estroma neoformado. O padrão histológico foi semelhante nos demais grupos. A análise histológica quantitativa demonstrou estatisticamente menor concentração de axônios regenerados no grupo B (veia autógena) do que a dos demais grupos. O grupo que utilizou veia autógena (sem glicerol) apresentou menor recuperação funcional quando comparado com os demais grupos para 3 e 6 semanas. O resultado funcional foi estatisticamente semelhante entre os grupos de veias preservadas (autógena e alógena) e o auto-enxerto / Nerve autografting is considered the best treatment for the restoration of great losses of peripheral nerve. In spite of adequate surgical treatment, functional deficits occur. Also, improvement in functional recuperation and decrease in sequelae are expected. There are many techniques aiming at this purpose. The interposition of tubular conduits, as a bridge between the ends of a sectioned nerve, among these the vein graft, is an alternative technique which offers theoretical advantages. The vein is a studied material as possible evaluated tubular conductor experimentally and in clinical cases. Recent studies have given importance in the use of tissues transplants stored in banks. Glycerol is used for tissue preservation, having been told to its use in nerves and vessels. However, it does not have studies of the use of glycerol reserved veins in as substitute of nerve graft. The purpose of this study was to compare, in rats, the neural regeneration degree, using qualitative and quantitative histological analysis and functional recovery, obtained after interposition of a nerve graft, autogenous vein, autogenous vein preserved in glycerol and allograft vein preserved in glycerol. A 5 mm neural gap in the fibular nerve of rats (Lewis breed) has been created under microsurgical techinique. Four groups of six animals each have been divided according to the treatment employed: Group A Î control group: replacement of the fibular nerve itself (autograft); Group B Î a 1omm segment of external jugular vein was interposed; Group C Î a preserved external jugular vein in glycerol 98% per 7 days was interposed in the fibular nerve gap; Group D - external jugular vein preserved in glycerol of Sprague-Dawley rats had been used equal form to group C in Lewis rats. The animals had been sacrificed after 6 weeks for accomplishment of the histological studies. The functional walking track analysis was performed after in the pre-op, and in the pos-op (immediately, 3 and 6 weeks). The control group (autograft) presented similar histological results to the groups of glycerol preserved veins (autogenous vein and allograft vein), however it presented a bigger perineural tecidual reaction and bigger presence of escape axonal if compared with all the groups. The use of autogenous vein without preservation demonstrated histological results with greater neoangiogenesis and presence of connective tissue inside the neo- formed stroma. Histological pattern was similar to other studied groups. Quantitative histological analysis showed statistically lower concentration of regenerated axons in group B (autogenous vein) than the other groups.The group that used autogenous vein (without glycerol) presented little functional recovery for 3 and 6 weeks. No statistical difference was seen between groups A (autograft) and groups C and C (preserved veins) in the degree of functional recovery

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No. of bitstreams: 1 alinedealmeidaperes.pdf: 4968992 bytes, checksum: b682ecc1e40f813d6f65a50bb5cd23a6 (MD5) Previous issue date: 2016-10-11 / Pesquisa delineada no método misto (estudos de caso com pessoas internadas para receber hemocomponentes; representações sociais do binômio usuário-profissional sobre o processo de punção venosa periférico em hemoterapia; coorte prospectiva com doadores de sangue para calcular a incidência de trauma vascular periférico; survey sobre a prática de punção desempenhada com profissionais de duas instituições e sobre o nível de satisfação de doadores de sangue sobre o processo de punção venosa para doação de sangue; e implicações da punção venosa periférica em hemoterapia para a enfermagem). Objetivou analisar as especificidades do processo de punção de vasos durante a captação e transfusão de hemocomponentes, a ocorrência de trauma vascular periférico na perspectiva do binômio usuário-profissional e as representações sociais de profissionais e doadores de sangue sobre o processo de punção realizado com fins hemoterápicos. Utilizados referenciais da Teoria das Representações Sociais (TRS) e Teoria do Cuidado Transpessoal de Jean Watson. Foram dois os cenários da investigação: hemocentro e instituição hospitalar de ensino em Minas Gerais. Delineamentos amostrais: 1) por tipicidade para estudo de caso com seis receptores de hemocomponentes; 2) seleção completa composta por 200 doadores de sangue de um hemocentro, cujas representações sociais sobre o processo de punção foram captadas nas abordagens processual e estrutural; 3) amostra de seleção completa composta de 62 profissionais oriundos de duas instituições, cujos usuários tiveram suas veias puncionadas para fins hemoterápicos e para captação de representações sociais e survey sobre a prática laboral de profissionais que puncionam veias; 4) amostra de seleção completa com 150 doadores que integraram uma coorte prospectiva e aferição de seu nível de satisfação sobre o processo de punção. Dados coletados de Junho/2015 a Agosto/2016. Estudo de caso e coortes estruturadas a partir de instrumento previamente validado, utilizando escalas mensurativas, paleta cromática e registros fotográficos de manifestações de trauma vascular. Utilizadas técnica de evocação livre a partir de termos indutores (―doar sangue‖, ―receber sangue‖ e ―punção da veia para doar sangue‖) para abordagem estrutural da TRS e gravação de áudio com entrevista semiestruturada para abordagem processual. Survey abordando práticas profissionais e aferição da satisfação de doadores quanto à punção. Atendidas recomendações éticas e legais da pesquisa com seres humanos. Integraram os estudos de caso pessoas com anemia, plaquetopenia e imunodepressão, cujos acessos venosos viabilizaram transfusões sanguíneas e infusão de terapia intravenosa. Detectada perda da punção havendo divergência entre registros profissionais e prática laboral. Complexo de fixação não atendeu aos protocolos institucionais. Foram manifestações de trauma vascular: edema e equimose. Atendidas recomendações sobre o calibre do cateter intravenoso e uso de vaso central para a infusão de drogas vesicantes. Abordagem processual das representações sociais de profissionais evidenciou três categorias temáticas que retrataram o processo de punção venosa. Técnica de evocação livre para etapas do processo hemoterápico evidenciou motivações do grupo para o ato de doação, proximidade com familiares e influência das informações compartilhadas sobre o comportamento de doadores. Identificado distanciamento do recebimento de sangue devido xviii falta de ancoragem em experiências próprias ou de terceiros. Registrado desconforto daqueles que doam sangue. Elementos simbólicos para o ato de doação e de se ter veia puncionada (―sensaçãoruim-desconforto‖, ―menor-dor‖, ―medo-ansiedade‖ e ―agulha-picada‖) retrataram representações semelhantes. Incidência de trauma vascular foi 6,7% com manifestações de dor e equimose. O survey com profissionais evidenciou sentimentos de ―sentir-se avaliado‖, ao longo das etapas da punção, ―alívio‖ ao término da punção e ―apreensão‖ no período de manutenção do acesso venoso. Foram comportamentos emergentes: ―vigilância‖ ao longo das etapas do processo e ―tagarelar‖. Aferição da satisfação dos doadores com a punção evidenciou escores ≥6/10, sendo a menor pontuação atribuída ao tempo de atendimento. Conclui-se sobre a existência de peculiaridades no processo de punção de vasos para fins hemoterápicos quando comparado à sua utilização para outras finalidades, sendo a coerência entre práticas laborais com: boas práticas, educação permanente dos profissionais e controle de eventos adversos que norteiam a reestruturação das ações terapêuticas fatores que justificam a incidência de trauma vascular de 6,7%. As implicações dos resultados para o cuidado de enfermagem, com base na Teoria do Cuidado Transpessoal, evidenciaram a necessidade de ressignificar a realização do processo de punção venosa periférico para as pessoas que o vivenciam e está em coerência com uma assistência de enfermagem que vise proporcionar um momento de cuidado autêntico aos usuários do contexto hemoterápico. / Outline research in a mixed method (case of study with hospitalized individuals to receive blood component; social representation of user-professional binomial involving the peripheral venipuncture process; prospective cohort with blood donator to calculate the peripheral venipuncture damage occurrence; survey about the puncture practice performed by professionals in two institutions and the satisfaction level of the blood donators with the venipuncture process for blood donation; and peripheral venipuncture implications in hemotherapy for nursing. The main goal is to analyze the venipuncture process specificities during withdrawal and transfusion of blood component, the peripheral venipuncture damage occurrence in a user-professional binomial approach and the social representation of professionals and blood donators in the venipuncture process performed for hemotherapy purposes. Was utilized Social Representation Theory’s references (SRT) and Jean Watson’s Human Caring Theory: Pertinent Transpersonal. Was two investigative scenarios: Hemocentro and Education Hospital Institute. Sampling Designs: 1) By types for case of study with six blood component receivers; 2) Completely selection composed by 200 blood donators of a Hemocentro, whom social representations about the venipuncture process were captured in the procedural and structural approach; 3) Sample of complete selection composed by sixty-two professionals from the two institutions. Which the users had venipuncture for the hemotherapy purposes and social representation gathering. Include professional’s venipuncture labor practice survey; 4) Sample of complete selection with a 150 donators which integrated a prospective cohort e standardization of satisfaction level in the puncture process. The data was collected from June/2015 to August/2016. Case of study and cohort were structured from an instrument previously authenticate. Was utilized measurable scale, chromatic palette, and photographic register of venous damage. Also, was utilized the free evocation technique from inductor terms: ―blood donation‖,‖ blood receiver‖, ―venipuncture for blood donation‖ for structure approach of (SRT) and audio record interview semi-structured for processual approach. Survey involving professional practice and measurement of donators satisfaction as the puncture. Was attended the ethical recommendations and statutory research with human beings. Integrate the Study’s case people with anemia, thrombocytopenia and immunosuppression people whom venous access allowed blood transfusion and venous therapy infusion. Was detected puncture loss involving divergence between professional register and labor practice. Dressing devices didn’t attempt the institute protocol. Was damage veins manifestations: edema and ecchymosis. Attended recommendations about gauge intravenous catheter and use of central vessel to infusion of vesicant drugs. The processual approach of professional’s social representation showed three thematic categories that reflects the venipuncture process. The free evocation technique for stages of the hemotherapeutic process showed group motivations for the donation act, proximity with relatives and the influence of shared information about the donor behavior. Was identified distancing from receiving blood due to lack of anchorage in own experiences or others. Was registered discomfort of those who donate blood. Symbolic elements to the act of donate and have punctured vein: ―bad feeling – uncomfortable‖, ―less pain‖, ―afraid-anxious‖, ―needle-sting‖, pictured similar representations. The vascular trauma incidence was 6,7% with manifestations of pain and ecchymosis. The professional’s survey showed feelings of ―relief‖ during the puncture steps, ―relief‖ at the puncture’s end, seizure during the maintenance of venous access. Were emerging behaviors: ―vigilance‖, along the process steps and ―chatter‖. Gauging the satisfaction of donors with the punch showed scores >= 6/10, being the lowest score assigned to the service time. Was concluded the existence of peculiarities in the vessel puncture xx process for hemotherapic purpose when compared to its use for other purposes, being the coherence between labor practices with: good practices, continuing professional’s education and control of adverse events that guide the restructuring of therapeutic actions. Factors that justify the incidence of vascular trauma by 6,7%. The implications of the results for nursing care, based on the Human Caring Theory: Pertinent Transpersonal, highlighted the need to reframe the completion of the peripheral venipuncture process for people who experienced and is coherent with a nursing care that aims to provide a moment of authentic care to the users of the hemotherapic context.

The cardiovascular system of bilaterians developed from a common ancestor. However, no endothelial cells exist in invertebrates demonstrating that primitive cardiovascular tubes do not require this vertebrate-specific cell type in order to form. This raises the question of how cardiovascular tubes form in invertebrates? Here we discovered that in the invertebrate cephalochordate amphioxus, the basement membranes of endoderm and mesoderm line the lumen of the major vessels, namely aorta and heart. During amphioxus development a laminin-containing extracellular matrix (ECM) was found to fill the space between the basal cell surfaces of endoderm and mesoderm along their anterior-posterior (A-P) axes. Blood cells appear in this ECM-filled tubular space, coincident with the development of a vascular lumen. To get insight into the underlying cellular mechanism, we induced vessels in vitro with a cell polarity similar to the vessels of amphioxus. We show that basal cell surfaces can form a vascular lumen filled with ECM, and that phagocytotic blood cells can clear this luminal ECM to generate a patent vascular lumen. Therefore, our experiments suggest a mechanism of blood vessel formation via basal cell surfaces in amphioxus and possibly in other invertebrates that do not have any endothelial cells. In addition, a comparison between amphioxus and mouse shows that endothelial cells physically separate the basement membranes from the vascular lumen, suggesting that endothelial cells create cardiovascular tubes with a cell polarity of epithelial tubes in vertebrates and mammals.

This work deals with possibilities of registration of retinal images from different mo-dalities, concretely optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO) and fundus camera. In first stage is the interest focused on registration of SLO and fundus images, which will serve to determine area of interest for consecutive registration of OCT data. The final stage is finding correct location of OCT B-scans in fundus image. On the basis of the studied methods of registration was chosen method making use of computation of correlation coefficient for both cases. For finding optimal parameters of registration is used searching through whole space of parameters. In partial stages of the work was created algorithm for alignment of B-scans followed by detection of blood vessels and also simple algorithm for detection of blood vessels from fundus image. For more transparent registration the graphical user interface was created, which allows loading input images and displaying the result in several possible forms.

En tredjedel av alla bypass-operationer leder till att kärlimplantaten slutar fungerar inom ettårs tid. En anledning till detta är bildandet av ogynnsam vävnad som sker i form av ärrbildning efter implantationen. Ärrvävnaden orsakar nya förträngningar vilket leder till ett försämrat blodflöde. Kärlimplantatet Y-graft har genom sin design som följer Murray´s lag, en naturlig blodflödesfördelning. Designen i form av ett Y har kunnat bekräftas vara fördelaktig då geometrin vid utflödet minskar risken för ärrbildning. Vad som saknas för att Y-graft ska kunna komma ut på marknaden är ett lämpligt material. Med detta som bakgrund uppkom syftet med litteraturstudien att undersöka vilka material meddokumenterad klinisk historik som är möjliga att använda vid textil tillverkning av Y-graft. Genom en gedigen litteratursökning med hjälp av sökverktyg som U.S. Food and Drug Administration (FDA) tillsammans med andra databaser inom de medicinska och materialtekniska områdena, har en förståelse skapats kring vilka material som används i medicintekniska produkter och som är möjliga kandidater till Y-graft. Litteraturstudien resulterade i att materialen polyetentereftalat, polybutentereftalat, polybutester polytetrafluoreten, polyester-, polyeter- och polykarbonatbaserade polyuretaner samt polypropen, polyeten, alfatisk polyamid och silke finns i godkända medicintekniska produkter på den amerikanska marknaden. De presenterade materialen har på så visdokumenterad klinisk historik och är lämpliga kandidater att använda vid textil tillverkning av Y-graft. De godkända materialkandidaterna som presenteras kan även beläggas medbiologiska polymerer för förbättrad biokompatibilitet. Materialkandidaterna har godkänts i medicintekniska produkter av U.S. Food and Drug Administration (FDA). Genom godkännandet har alla de presenterade materialen dokumenterad klinisk historik och är där med lämpliga kandidater att använda vid textiltillverkning av Y-graft. / One third of all bypass surgeries causes vascular implants to stop working within a year. A reason for this is the formation of unfavorable tissue that occurs in the form of scarring after implantation. The scar tissue causes new constrictions, which leads to impaired blood flow. The vascular implant Y-graft, by design follows Murray's law and therefore has a natural blood flow distribution. The design in the form of a Y has been confirmed to be advantageous. The Y geometry at the outflow reduces the risk of scarring. What is missing for Y-graft to be able to enter the market is a suitable material. With this as a background, the purpose of the literature study was to investigate which materials with documented clinical history can be used in textile production of Y-graft. Through a thorough literature search, using search tools like the U.S. Food and Drug Administration (FDA) together with other databases in the medical and material engineering fields, an understanding has been created about which materials are used in medical technology products and which are potential candidates for Y-graft. The literature study concluded that the materials polyethylene terephthalate, polybutheneterephthalate, polybutester polytetrafluoroethylene are found in approved medical technology products in the United States. Polyester, polyether and polycarbonate based polyurethanes and polypropylene, polyethylene, alphatic polyamide and silk are also found in the United States medical market. These presented materials thus have documented clinical history and are suitable candidates for use in textile manufacturing of Y-graft. The approved material candidates presented can also be coated with biological polymers for improved biocompatibility. The material candidates have been approved in medical technology products by the U.S. Food and Drug Administration (FDA). With this approval, all the presented materials have documented clinical history and are therefore suitable candidates to use when manufacturing Y-graft.

Vascular Endothelial Growth Factor Receptor-3 (VEGFR3/Flt4) and its ligand Vegfc are necessary for development of both blood and lymphatic vasculature in vertebrates. In zebrafish, Vegfc/Flt4 signaling is essential for formation of arteries, veins, and lymphatic vessels. Interestingly, Flt4 appears to utilize distinct signaling pathways during the development of each of these vessels. To identify components of this pathway, we performed a transgenic haploid genetic screen in zebrafish that express EGFP under the control of a blood vessel specific promoter. As a result, we indentified a mutant allele of vascular endothelial growth factor c (vegfc), vegfcum18. vegfcum18 mutants display defects in vein and lymphatic vessel development but normal segmental artery (SeA) formation. Characterization of this allele led to the finding that the primary defect in vegfcum18 mutants was a general failure in vein and lymphatic vessel sprouting. Further genetic and biochemical analysis of this mutant revealed profound paracrine defects, which likely result in the observed loss of lymphatic and venous structures. Furthermore, double mutant analysis demonstrated that defects during SeA formation in vegfcum18 mutants were masked by inputs from the Vegfa signaling pathway. Endothelial cell autonomous expression of vegfcum18 induced angiogenic effects on blood vessels while endothelial cells lacking vegfc displayed defects in tip cell occupancy, suggesting a cell autonomous-autocrine role for Vegfc during developmental angiogenesis. Finally, we present genetic evidence that links processing of Vegfc by Furin during the formation of lymphatics in zebrafish. Together the data presented here suggest two discrete modes of signaling during blood and lymphatic vessel development, thus implying that regulation of Vegfc secretion and processing may play a pivotal role in the formation of these distinct vessel types in zebrafish.

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