Resumo: Este projeto visa à análise cinemática de um arranjo experimental capaz de reproduzir o fluxo sanguíneo em artérias. O mecanismo procura realizar esse escoamento através de um sistema came-seguidor juntamente com um sistema hidráulico, utilizando êmbolo e duas válvulas controladoras de fluxo. O mecanismo came-seguidor será utilizado devido a sua versatilidade em garantir que o escoamento sanguíneo ocorra durante um ciclo cardíaco. A came será radial com seguidores de roletes. O seguidor de roletes será ligado ao cilindro hidráulico que controla o fluxo sanguíneo. Um tubo de látex foi acoplado ao sistema hidráulico representando a aorta abdominal, foi confeccionado com as dimensões reais desta artéria e o látex foi escolhido, pois possui um coeficiente de elasticidade muito próximo da artéria. Um manômetro foi acoplado ao sistema para medir a pressão no interior do tubo de látex. Na sequência um tubo de complacência simular as perdas de carga do sistema circulatório. O deslocamento radial do tubo de látex e variação de pressão do manômetro foram monitorados através de filmagem. Posteriormente, os resultados experimentais foram comparados e validados com os resultados numéricos obtidos com o programa ANSYS e com a literatura / Abstract: This project aims to kinematic analysis of an experimental apparatus able to reproduce the blood flow in arteries. The mechanism cam-follower and the hydraulic system using piston and two controlling valves of flow were used to realize the fluid flow. The camfollower mechanism was used to ensure that the fluid flow occurs during the cardiac cycle. The cam is radial with roller followers. The follower roller is connected to the hydraulic cylinder which controls the fluid flow. A latex tube was attached to the hydraulic system representing the abdominal aorta. The latex tube has the same real dimensions of this artery and it was chosen due the modulus of elasticity very close to the artery. A manometer was used to measure the outlet pressure of latex tube. After latex tube there is a complacency tube to control the pressure drop of circulatory system. The radial displacement of the latex tube and pressure variation of the manometer were monitored through filming. The experimental results were compared and validated with numerical results obtained with ANSYS software and with literature / Orientador: Aparecido Carlos Gonçalves / Coorientador: Amarildo Tabone Paschoalini / Banca: João Antonio Pereira / Banca: Cleudmar Amaral de Araújo / Mestre

Orientador: Reinaldo Wilson Vieira / Tese (doutorado)- Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T08:18:06Z (GMT). No. of bitstreams: 1 VieiraJunior_FranciscoUbaldo_D.pdf: 9716061 bytes, checksum: 94d31e9715d7d77c249963888ed77562 (MD5) Previous issue date: 2009 / Resumo: Introdução: Dentre os equipamentos utilizados em circulação extracorpórea, as bombas de roletes têm grande importância, com modelos disponíveis de vários fabricantes. O ajuste dos roletes é um fator importante nas taxas de hemólise e o potencial hemolítico difere em cada um deles. Pesquisadores nem sempre abordam detalhes sobre os perfis do leito rígido supondo que as formas padronizadas de ajuste garantem valores iguais e comparáveis para todos os modelos de bombas de roletes. Dispomos principalmente de dois métodos para o ajuste de bombas de roletes e nenhum deles considera as características de impulsão do fluido, definida pelo perfil do leito rígido. Objetivo: O objetivo desse trabalho é analisar o perfil hidrodinâmico de três diferentes modelos de bombas de roletes comercializados no Brasil e sua influência no fluxo e refluxo. Materiais e Métodos: Foram utilizados tubos de silicone de 9,5x1,6; 9,5x2,4; 13x2,4 mm de diâmetro de dois fornecedores diferentes. Os testes foram realizados em solução fisiológica e solução análoga ao sangue. O perfil hidrodinâmico de três bombas de roletes foi realizado por medidas de velocidade de queda e calibração dinâmica. Foi investigada a variação das medidas de velocidade de queda com o tempo e testes de compressão em equipamento servo-hidráulico. Os refluxos foram visualizados em aspirador de sangue e reservatório de cardiotomia com medidas simultâneas. Resultados: Os perfis hidrodinâmicos apresentaram diferenças em suas variâncias para medidas de velocidade de queda (P<0,01) e calibração dinâmica (P<0,0001). A tensão residual nos tubos de silicone ocasionou redução nas medidas de velocidade de queda com o tempo (P<0,0002) e foram confirmadas pelos testes de compressão (P<0,0001). Conclusão: Os ajustes realizados pelos métodos de velocidade de queda e calibração dinâmica são dependentes da forma do leito rígido. Comparações envolvendo bombas de roletes devem ser feitas com cautela. A tensão residual em tubos de silicone compromete a repetitividade dos ajustes feitos pelo método de velocidade de queda. / Abstract: Introduction: Among the equipment used in cardiopulmonary bypass, roller pumps have great importance, with models available from several manufacturers. The roller adjustment is an important factor in the rates of hemolysis and the hemolytic potential differs in adjustment. Researchers do not always address details on the profiles of the raceway accepting that the forms of standardized settings ensure equal and comparable values for all models of roller pumps. There are two methods for setting roller pumps and none considers the dynamic characteristics of the fluid, defined by the profile of the raceway. Objective: The aim of this study is to analyze the hydrodynamic profile of three different models of roller pumps commercialized in Brazil and its influence on the flow and back flow. Materials and methods: We used silicone tubes of 9.5x1.6, 9.5 x2.4 and 13x2.4 mm in diameter from two different suppliers. The tests were performed in saline and solution analogous to blood. The hydrodynamic profile in three roller pumps was achieved by measurements of drop rate and dynamic calibration. The drop rate variations were investigated in silicone tubes by measurements of drop rate and the compression tests in servo-hydraulic equipment. Retrograde flows were viewed in blood aspirator and cardiotomy reservoir. Results: The hydrodynamic profiles showed differences in their variances for measurements of drop rate (P <0.01) and dynamic calibration (P <0.0001). The residual stress in the silicone tubes caused reduction in drop rate with time (P<0.0002) and were confirmed by compression tests (P <0.0001). Conclusion: The adjustments made by the methods of drop rate and dynamic calibration are dependent on the raceway profile. Comparisons involving roller pumps must be made with caution. The residual stress in the silicone tubes compromises repeatability of adjustments made by the drop rate method. / Doutorado / Pesquisa Experimental / Doutor em Cirurgia

Lors d'une lésion vasculaire, les plaquettes adhèrent, s’activent et agrègent pour former un clou hémostatique qui stoppe le saignement. Dans un contexte pathologique, l’agrégation plaquettaire mène à la formation d’un thrombus qui peut obstruer une artère malade et entrainer des pathologies ischémiques graves. Les agents antiplaquettaires actuels, qui ciblent l’activation et l’agrégation des plaquettes, ont une efficacité reconnue, mais ont pour limites, la récurrence d'événements ischémiques et le risque hémorragique. L’objectif central de ma thèse a été d’explorer l’importance des étapes initiales d’adhérence des plaquettes aux protéines sous-endothéliales et du rôle du flux sanguin dans l’agrégation des plaquettes. J’ai pu montrer qu’un anticorps dirigé contre la GPIbβ, RAM.1, réduit la signalisation du complexe GPIb-V-IX et la formation de thrombi sans affecter l'hémostase. J’ai également mis en évidence que la fibronectine cellulaire fibrillaire est une surface thrombogène qui assure l’adhérence, l'activation, l'agrégation et l'activité pro-coagulante des plaquettes. Enfin, mes travaux indiquent que la pulsatilité du flux sanguin possède un rôle inverse sur la croissance des thrombi en conditions physiologique et pathologique. En conclusion, ce travail met en lumière l’importance des étapes initiales d’adhérence des plaquettes et de la pulsatilité du flux sanguin dans l’agrégation plaquettaire. / Following vascular injury, blood platelets adhere, become activated and aggregate to form a hemostatic plug which stops the bleeding. In a pathological context, platelet aggregation can also lead to the formation of an occlusive thrombus, responsible for lifethreatening ischemic events. Current antiplatelet drugs targeting platelet activation and aggregation, have a recognized efficacy, but also present some limitations including the recurrence of ischemic events and the risk of bleeding. The aim of my thesis was to explore the importance of the initial step of platelet adhesion to subendothelial proteins and the role of pulsatile blood flow in platelet aggregation. I provided evidence that RAM.1 an antibody directed against GPIbβ, reduces GPIb signaling and thrombus formation without affecting hemostasis. My work also showed that fibrillar cellular fibronectin is a thrombogenic surface which supports efficient adhesion, activation, aggregation and procoagulant activity of platelets. Finally, I observed that the pulsatility of the blood flow has an inverse role in the growth of thrombi in physiological and pathological settings. In conclusion, this work highlights the importance of initial stages of platelet adhesion and of the blood flow pulsatility in platelet aggregation.

<div>The thesis includes two application studies of computational fluid dynamics. The first is new and efficient drug delivery to the posterior part of the eye, a growing health necessity worldwide. Current treatment of eye diseases, such as age related macular degeneration (AMD), relies on repeated intravitreal injections of drug-containing solutions. Such a drug delivery has significant drawbacks, including short drug life, vital medical service, and high medical costs. In this study, we explore a new approach of controlled drug delivery by introducing unique porous implants. Computational</div><div>modeling contains physiological and anatomical traits. We simulate the IgG1 Fab drug delivery to the posterior eye to evaluate the effectiveness of the porous implants to control the drug delivery. The computational model was validated by established computation results from independent studies and experimental data. Overall, the results indicate that therapeutic drug levels in the posterior eye are sustained for</div><div>eight weeks, similar to those performed with intravitreal injection of the same drug. We evaluate the effects of the porous implant on the time evaluation of the drug concentrations in the sclera, choroid, and retina layers of the eye. Subsequent simulations were carried out with varying porosity values of a porous episcleral implant.</div><div>Our computational results reveal that the time evolution of drug concentration is distinctively correlated to drug source location and pore size. The response of this porous implant for controlled drug delivery applications was examined. A correlation between porosity and fluid properties for the porous implants was revealed in this study. The second application lays in the computational modeling of the oscillating flow in rectangular ducts. This computational study has further applications in investigating the fluid flow motion in bodily organs. It can be useful in studying the</div><div>response of bone cells to the wall shear stress in the human body. </div>

This present thesis comprise two major parts both experimental and numerical study which have been conducted in four distinct steps as following: (1) Design, construction, and evaluation of control and hydrodynamic of a bioreactor system. (2) Visualization of fluid flow perfusion in the hollow fibre membrane bioreactor (HFMB) using a biomedical noninvasive imaging technique, i.e. positron emission tomography (PET). (3) Development of a mathematical model for analyzing a hybrid hollow fibre membrane bioreactor (hHFMB) and (4) Development of a dynamic and two-porous media model for analyzing the HFMB with the aid of computational fluid dynamics (CFD), specifically for bone tissue engineering application. The experimental part includes the steps 1 and 2. In the step 1, the flow perfusion bioreactor system has been designed and constructed. The experimental evaluations of hydrodynamic, and control were performed. In this system, mean pressure, mean flow rate, frequency and waveform of the pulsatile pressure and flow rate can be modulated and controlled over the time to simulate both physiological and non-physiological conditions. The temperature, dissolved oxygen, and pH can be controlled.This bioreactor system can be applied to a variety of scaffold configurations, geometries, and sizes as the cell/tissue culture chamber is adjustable in length.This system is autoclavable, and compatible with noninvasive medical imaging techniques. Designing of the inlet and outlet manifold of the bioreactor were performed according to data obtained from CFD simulation of the flow distribution to achieve high efficiencies in the uniformity of flow perfusion. In the second step, PET was proposed for the very first time and a small animal PET system was used to obtain new information about steady and pulsatile flow patterns in the HFMB for tissue engineering applications. The non-homogeneous tracer distribution, as found with PET imaging, implies the occurrence of non-efficient regions with respect to mass transfer. In steady inlet flow condition, a non-uniform distribution of radioactive tracer was obtained. In contrast, the pulsatile inlet flow generated more uniform perfusion than that of steady flow. Further, it was found that in the case of pulsatile flow, the accumulation of the tracer within the bioreactor was efficiently less than that of steady inlet flow at the same condition. Therefore, in one hand these findings have the potential to improve bioreactor design and in the other hand can explore a very important rout to employ PET in developing bioreactors for tissue engineering applications. The numerical part includes the step 3 and 4 in which the numerical study has been performed for 3-D bone tissue growth in HFMB as a case study for large-scale tissue culture. In the step 3, the feasibility of utilizing newly proposed hHFMB for the growth of mesenchymal stem cells (MSCs) to form bone tissue was investigated using numerical simulations. To this aim, a mathematical model using a CFD code was developed to optimize the design and operation parameters of hHFMB for the growth of MSCs. The volume averaging method was used to formulate mass balance for the nutrients and the cells in the porous extracapillary space (ECS) of the hHFMB. The cell-scaffold construct in the ECS of the hollow fibres and membrane wall were treated as porous medium. Cell volume fraction dependent porosity, permeability, and diffusivity of mass were used in the model. The simulations allowed the simultaneous prediction of nutrient distribution and nutrient-dependent cell volume fraction. In addition, this model was used to study the effects of the operating and design parameters on the nutrient distribution and cell growth within the bioreactor. The modeling results demonstrated that the fluid dynamics within the ECS and transport properties and uptake rates in hHFMB were sufficient to support MSCs required for clinical-scale bone tissue growth in vitro and enabled to solve nutrition difficulties because of high cell density and scaffold size. In the step 4, the new dynamic and two-porous media model has been used for analyzing the nutrient-dependent MSCs growth in order to form the bone tissue in the HFMB. In the present model, hollow fibre scaffold within the bioreactor was treated as a porous domain. The domain consists of the porous lumen region available for fluid flow and the porous ECS region, filled with collagen gel containing cells, for growing tissue mass. Furthermore, the contributions of several design and process parameters, which enhance the performance of the bioreactor, were studied. In addition, the dynamic evaluation of cell growth, oxygen and glucose distributions were quantitatively analyzed. The obtained information can be used for better designing of the bioreactor, determining of suitable operational conditions and scale up of the bioreactor for engineering of clinical-scale bone tissue.--Résumé abrégé par UMI.

Objetivo: Medir a pulsatilidade da parede do aneurisma de aorta humano antes e depois de sua correção endoluminal. Método: Cinco aneurismas foram submetidos à perfusão pulsátil antes e depois do implante de uma endoprótese. Resultado: o nível da coluna de água oscilou durante a pulsação com variações de 17, 16, 13, 7 e 25 cm antes da colocação da endoprótese. Depois da prótese, a oscilação diminuiu em todos os casos para 13, 12, 9, 3,5 e 23 cm, respectivamente. Conclusão: A pulsação da endoprótese é transmitida à parede do aneurisma / Objective: To measure the pulsatility of human aortic aneurysms before and after exclusion with endograft. Method: Five aneurysms were submitted to pulsatile perfusion before and after implantation of a bifurcated endograft. Result: The level of the water column oscillated during pulsation, in each case, with an amplitude of 17, 16, 13, 7 and 25 cm before the endograft insertion. After that, the amplitudes dropped to, respectively 13, 12, 9, 3.5 and 23 cm.Conclusion: Pulsation of an endograft is transmitted to the aneurysm wall even in the absence of endoleak

Objetivo: Medir a pulsatilidade da parede do aneurisma de aorta humano antes e depois de sua correção endoluminal. Método: Cinco aneurismas foram submetidos à perfusão pulsátil antes e depois do implante de uma endoprótese. Resultado: o nível da coluna de água oscilou durante a pulsação com variações de 17, 16, 13, 7 e 25 cm antes da colocação da endoprótese. Depois da prótese, a oscilação diminuiu em todos os casos para 13, 12, 9, 3,5 e 23 cm, respectivamente. Conclusão: A pulsação da endoprótese é transmitida à parede do aneurisma / Objective: To measure the pulsatility of human aortic aneurysms before and after exclusion with endograft. Method: Five aneurysms were submitted to pulsatile perfusion before and after implantation of a bifurcated endograft. Result: The level of the water column oscillated during pulsation, in each case, with an amplitude of 17, 16, 13, 7 and 25 cm before the endograft insertion. After that, the amplitudes dropped to, respectively 13, 12, 9, 3.5 and 23 cm.Conclusion: Pulsation of an endograft is transmitted to the aneurysm wall even in the absence of endoleak

Hemolysis assessment of heart pumps is necessary to be carried out before progressing to clinical trials. Blood pump hemolysis assessment standards, such as ASTM F1830 and F1841, were initially based on continuous flow pumps and included the pulsatile flow pumps later in 2019. However, a lack of guidance on the test rig design results in diverse rigs being applied in literature and companies. An aluminum-profile-based rig, which was named the old rig in this study, was created based on Gräf’s mock loop for pulsatile flow pumps in the literature. Nevertheless, this rig was without a user-friendly interface for blood-filling and de-airing, and it led to a risk of blood leakage, more effort required, and a chance of more hemolysis induced during the processes. Thus, this thesis aims to create a new rig for pulsatile flow pumps and improve its usability for blood filling and de-airing. To achieve the goals, a new rig design concept and its prototype were generated through the design thinking process. Next, user experience testings with the tasks, rig filling, de-airing, and emptying, were given to 5 users to validate if the features of the new rig could satisfy the user needs and improve the usability in terms of efficiency and user satisfaction. Lastly, two blood tests were conducted with the paired rigs, the old rig, and the new rig, based on the same pulsatile flow pump prototypes to investigate the impact of the new system layout on the hemolysis assessment. The results from the user experience testing showed that the new rig had a higher efficiency mainly based on the positive qualitative feedback of the users. The average satisfaction scores in all three tasks were higher on the new rig than on the old rig. Furthermore, the new rig did not induce more hemolysis than the old rig based on the two blood tests. Though the results were not statistically significant, the new rig could be a potential reference for a new standard of hemolysis testing on pulsatile blood pumps with user-friendly blood filling and de-airing processes. / Hemolys bedömning av hjärtpumpar är nödvändigt att utföras innan fortsättning till kliniska tester. Blodpump hemolys bedömning standarder, såsom ASTM F1830 och F1841, var initialt baserade på kontinuerliga flödespumpar, men sedan 2019 har även pulserande pumpar blivit inkluderadeDock, ingen klar vägledning av test rigg design, resulterar i att diverse riggar har använts i litteraturen och företag. En aluminiumprofilbaserad rigg, som i denna studie fick namnet den gamla riggen, skapades utifrån Gräfs mock loop för pulserande flödespumpar i litteraturen. Ändå saknade denna rigg ett användarvänligt gränssnitt för blodfyllning och avluftning, och det ledde till risk för blodläckage, mer ansträngning som krävdes och en chans att mer hemolys inducerades under processerna. Således, syftet med denna avhandling är att skapa en ny rigg för pulserade flödespumpar och förbättra användbarheten för blodfyllning och avluftning. För att uppnå målet, generades en ny rigg design koncept och dess prototyp genom designtänkande processen. Sedan, gavs följande användarupplevelse uppgifter, riggfyllning, avluftning och tömning till 5 användare för att validera om funktionerna på den nya riggen kunde uppfylla användarens behov och förbättra användbarheten gällande effektivitet och användarnöjdhet. Slutligen, genomfördes två försök med blod med de parade riggarna, gamla riggen och den nya riggen, baserat på samma pulserade flödespump prototyp för att undersöka det nya systemets layout påverkan på hemolys bedöming. Resultatet från användarupplevelse försöken visade att den nya riggen hade högre effektivitet vilket främst baserades på den kvalitativa återkopplingen från användarna. Den genomsnittliga tillfredsställelsen i alla tre uppgifter var högre med den nya riggen än med gamla riggen. Det var ingen ökning av hemolys i den nya riggen, baserat på de två blodförsöken. Trots att resultaten inte var statiskt säkerställt, så visade det sig vara en potentiell referens för en ny standard för hemolystestning på pulserade blodpumpar med användarvänliga blodfyllnings- och avluftningsprocesser.

No abstract provided. / Thesis / Master of Engineering (MEngr) / Scope and contents: This thesis describes the behaviour of iron ore-water suspensions under turbulent flow conditions. This work is divided into two parts. Part I deals with the regimes of transport under steady state flow conditions in circular and horizontal ducts. The heterogeneous flow regime is extensively analyzed; a sequential discrimination of models with an oriented design of experiments have permitted the determination of the best model to correlate hydraulic gradients for these suspensions. A critical discussion on the limit deposit conditions is also included. Part II describes the behaviour of clear water under oscillatory flow conditions. The study demonstrates that the quasi-steady state hypothesis, i.e., fully developed flow assumption, applied to pulsatile turbulent flow under the conditions studied. Observations on the behaviour of iron ore-water suspensions under pulsatile flow are also included. The experiments were carried out using a new air-pulsing technique.

The thesis deals with the flow in pipe bends and radial turbines geometries that are commonly found in an Internal Combustion Engine (ICE). The development phase of internal combustion engines relies more and more on simulations as an important complement to experiments. This is partly because of the reduction in development cost and the shortening of the development time. This is one of the reasons for the need of more accurate and predictive simulations. By using more complex computational methods the accuracy and predictive capabilities are increased. The disadvantage of using more sophisticated tools is that the computational time is increasing, making such tools less attractive for standard design purposes. Hence, one of the goals of the work has been to contribute to assess and improve the predictive capability of the simpler methods used by the industry. By comparing results from experiments, Reynolds Averaged Navier-Stokes (RANS) computations, and Large Eddy Simulations (LES) the accuracy of the different computational methods can be established. The advantages of using LES over RANS for the flows under consideration stems from the unsteadiness of the flow in the engine manifold. When such unsteadiness overlaps the natural turbulence the model lacks a rational foundation. The thesis considers the effect of the cyclic flow on the chosen numerical models. The LES calculations have proven to be able to predict the mean field and the fluctuations very well when compared to the experimental data. Also the effects of pulsatile exhaust flow on the performance of the turbine of a turbocharging system is assessed. Both steady and pulsating inlet conditions are considered for the turbine case, where the latter is a more realistic representation of the real flow situation inside the exhaust manifold and turbine. The results have been analysed using different methods: single point Fast Fourier Transforms (FFT), probe line means and statistics, area and volume based Proper Orthogonal Decomposition (POD) and Dynamic Mode Decomposition (DMD). / Denna avhandling behandlar flödet i rörkrökar och radiella turbiner som vanligtvis återfinns i en förbränningsmotor. Utvecklingsfasen av förbränningsmotorer bygger mer och mer på att simuleringar är ett viktigt komplement till experiment. Detta beror delvis på minskade utvecklingskostnader men även på kortare utevklningstider. Detta är en av anledningarna till att man behöver mer exakta och prediktiva simuleringsmetoder. Genom att använda mer komplexa beräkningsmetoder så kan både nogrannheten och prediktiviteten öka. Nackdelen med att använda mer sofistikerade metoder är att beräkningstiden ökar, vilket medför att sådana verktyg är mindre attraktiva för standardiserade design ändamål. Härav, ett av målen med projektet har varit att bidra med att bedöma och förbättra de enklare metodernas prediktionsförmåga som används utav industrin. Genom att jämföra resultat från experiment, Reynolds Averaged Navier-Stokes (RANS) och Large Eddy Simulations (LES) så kan nogrannheten hos de olika simuleringsmetoderna fastställas. Fördelarna med att använda LES istället för RANS när det gäller de undersökta flödena kommer ifrån det instationära flödet i grenröret. När denna instationäritet överlappar den naturligt förekommande turbulensen så saknar modellen en rationell grund. Denna avhandling behandlar effekten av de cykliska flöderna på de valda numeriska modellerna. LES beräkningarna har bevisats kunna förutsäga medelfältet och fluktuationerna väldigt väl när man jämför med experimentell data. Effekterna som den pulserande avgasströmning har på turboladdarens turbin prestanda har också kunnat fastställas. Både konstant och pulserande inlopps randvillkor har används för turbinfallet, där det senare är ett mer realistiskt representation av den riktiga strömningsbilden innuti avgasgrenröret och turbinen. Resultaten har analyserats på flera olika sätt: snabba Fourier transformer (FFT) i enskilda punkter, medelvärden och statistik på problinjer, area och volumsbaserade metoder så som Proper Orthogonal Decomposition (POD) samt Dynamic Mode Decomposition (DMD). / <p>QC 20140919</p>