Tissue engineered heart valve (TEHV) is believed to be a promising candidate for curative heart valve replacements. Collagen, elastin and chondroitin-4-sulfate (C4S) comprise the extra-cellular matrix (ECM) of native heart valves and therefore are suitable materials for TEHV scaffolds. Freeze-drying technique was able to produce scaffolds with relative densities of 0.3%-2.0% and pore sizes of 33.2µm-201.5µm, without having any major effects on the ultra-structures on the scaffold materials. Subsequent dehydrothermal (DHT) treatment and ultra-violet (UV) irradiation introduced inter- or intra-molecular crosslinks in the scaffolds in forms of ester and amide bonds, as well as the accompanying denaturation of the proteins (i.e. ultra-structure transition from helices to random coils). The collagen-based scaffolds had tensile, compressive and effective bending moduli ranging from 39.8kPa to 1082kPa, from 2.4kPa to 213.9kPa, and from 11.0kPa to 415.8kPa, respectively. The different behaviours of the wall stretching and the wall buckling in the individual pores of the scaffolds contributed to the different tensile, compressive and bending moduli. The mechanical properties could be tailored through controlling the freezing temperature, the relative density and the composition of the scaffolds. A lower freezing temperature might lead to lower mechanical properties because different pore structures were introduced. When the the relative density of the scaffold increased, the values of the moduli increased exponentially, with an exponential dependence factor larger for the compressive modulus than for the tensile modulus. Adding elastin or C4S into the collagen scaffolds lowered the mechanical properties due to the decrease in the collagen content. Layered structures that combined collagen-rich layers with elastin-rich and/or C4S -rich layers allowed the scaffolds to make use of the different mechanical properties of different layers, and hence to show anisotropic bending behaviour depending on the loading directions. The lower effective bending modulus (9.6 to 25.0kPa) in the with curvature (WC) direction than that (18.1kPa to 39.3kPa) in the against curvature (AC) direction mimicked the characteristic behaviour of the native heart valves and would be beneficial for a mechanically desirable TEHV. The DHT treatment and UV irradiation were able to increase the mechanical properties of the scaffolds to up to 2.5 times of the original values, by reinforcing the scaffold materials with more crosslinks. In the hydrated status, the hydrophilic C4S improved the water uptake ability of the scaffold and the hydrophobic elastin reduced it. The hydrated layered scaffolds still exhibited bending anisotropy despite much lower effective bending modulus. Finite element models of the scaffolds produced results that were in agreement with the experiments, and enabled us to perform distributed loading and internal stress analysis on the scaffolds. The collagen-based scaffolds were seeded with cardiosphere-derived cells (CDCs), and they attached to the scaffolds and showed visible cell division, proliferation and migration. The CDCs exhibited preferred proliferation behaviours on the collagen-C4S scaffolds to that on the collagen-elastin scaffolds because of the cell affinity to the C4S, as well as the elastin-induced contractile cell phenotype and scaffold volume shrinkage. This difference seemed to be less evident in the layered scaffolds due to the cell communication between the layers. The crosslinking process also had effects on the cell proliferation in the ways that it induced ultra-structure changes or volume shrinkage in the scaffolds. The layered scaffold-cell constructs designed and produced in this study served as a forwarding step towards a mechanically desirable and biologically active TEHV.

Transcatheter aortic valve implantation (TAVI) is an effective alternative treatment option for patients with severe aortic stenosis, who are at a high risk for conventional surgical aortic valve replacement or considered inoperable. Despite the short- and mid-term survival benefits of TAVI, adverse clinical events, such as paravalvular leak, aortic rupture, and coronary occlusion, have been reported extensively. Many of these adverse events can be explained from the biomechanics perspective. Therefore, an in-depth understanding of biomechanical interaction between the device and native tissue is critical to the success of TAVI. The objective of this thesis was to investigate the biomechanics involved in the TAVI procedure using patient-specific finite element (FE) simulations. Patient-specific FE models of the aortic roots were reconstructed using pre-procedural multi-slice computed tomography images. The models incorporated aged human aortic material properties with material failure criteria obtained from mechanical tests, and realistic stent expansion methods. TAV deployment and tissue-device interaction were simulated; and the simulation results were compared to the clinical observations. Additionally, parametric studies were conducted to examine the influence of the model input on TAVI simulation results and subsequently the potential clinical complications such as paravalvular leak, annular rupture, and coronary artery occlusion. The methodology presented in this thesis could be potentially utilized to develop valuable pre-procedural planning tools to evaluate device performance for TAVI and eventually improve clinical outcomes.

The presented innovative magnetic testing method utilises the fact, that each commercially available electromagnet can not only be used as an actuator, but also comprises internal sensor functions. This allows a huge application variety in the fields of non-destructive testing and condition monitoring of electromagnetic systems during production and within the application in the field.

No description available.

Calcific aortic valve disease (CAVD) is associated with increased presence of myofibroblasts, osteoblastic cells and, occasionally, adipocytes and chondrocytes in lesions. The ectopic cell types in diseased valves may be elaborated by an unidentified multipotent progenitor subpopulation within the valve interstitial cells (VICs) that populate the valve interstitium. Notably, lesions form preferentially in the fibrosa layer, the stiffer layer of the valve leaflet. It has been shown that differentiation of VICs to myofibroblasts and osteoblasts is modulated by matrix stiffness. However, the molecular mechanisms involved in mediating stiffness-dependent mechanotransduction remain obscure. The objectives of this thesis were: (1) to determine whether VICs contain a subpopulation of multipotent mesenchymal progenitor cells and to measure the frequencies of the mesenchymal progenitors and osteoprogenitors; (2) to determine the role of β-catenin and matrix stiffness in transforming growth factor-β1 (TGF-β1)-induced myofibroblast differentiation of VICs; and (3) to preliminarily investigate the involvement of four and a half LIM domains protein 2 (FHL2) in CAVD and stiffness-dependent mechanotransduction downstream of RhoA in VICs. Firstly, VICs were found to contain a subpopulation of mesenchymal progenitors that are inducible to osteogenic, myofibroblastic, adipogenic, and chondrogenic lineages. The frequencies of mesenchymal progenitors and osteoprogenitors were significantly higher than other reported sources. Secondly, it was demonstrated that β-catenin is required in TGF-β1-induced, matrix stiffness-regulated myofibroblast differentiation. Notably, TGF-β1 was only able to induce β-catenin nuclear translocation and myofibroblast differentiation on matrices with fibrosa-like stiffness, but not on matrices with ventricularis-like stiffness. Thirdly, FHL2 was found to be upregulated and colocalized with runt-related transcriptional factor 2 (Runx2) in lesions in the fibrosa layer of diseased valves, suggesting its role in osteogenic processes in CAVD. Notably, increasing matrix stiffness increased FHL2 nuclear translocation and RhoA activity in VICs. Preliminary data showed that matrix stiffness regulates FHL2 nuclear translocation via RhoA activity. These results suggest that differentiation of the rich valve progenitor subpopulation, regulated by both mechanical and biochemical cues, may contribute to the preferential occurrence of ectopic cell types in the fibrosa in CAVD. More broadly, these results highlight the critical role of mechanical environment in modulating cellular biochemical signaling.

This thesis details a 1-d model of a lymphatic vessel, developed from a model by Reddy. Some additions to the modelling techniques were found to be necessary to prevent numerical phenomena not found in experiment. Furthermore the details of the wall and valve were important to the mechanics of the system. This developed model presents flow characteristics which are not represented in the existing lumped parameter or 1-d models of the lymphatic system. Additional terms allow more realistic representation of some modes of flow such as those occurring during collapse. The model was validated using Poiseuille flow calculations and experimental work. Features found in experiment were reproduced in the model. Such as the shark tooth shape of the radius time graph. A study of the sensitivity of the model to experimental parameters was performed. Features that increased flow included: increased compliance of the vessel, a larger diameter, amplitude of contraction or frequency, or a faster contraction wave. A lumped parameter model, relating the radius directly to the pressure, was investigated but this did not reproduce flow features such as the shark tooth shaped radius with time relationship or the radius peak at the beginning of a contraction or passive relaxation of the vessel. In the 1-d model the time constant of this passive relaxation increased with the magnitude of contraction. This value may have physiological relevance.

In der vorliegenden Studie wurden die prä- und postoperativen transthorakalen echokardiographischen Untersuchungen von 31 Patienten mit Mitralklappenrekonstruktion im Zeitraum von 2007 bis 2011 retrospektiv analysiert. Es wurden die Untersuchungen eingeschlossen, bei denen sowohl vor als auch nach dem operativen Eingriff das Bilddatenmaterial komplett zur Verfügung stand. Die echokardiographische Dokumentation der im klinischen Alltag durchgeführten Untersuchungen ermöglichte die Evaluation der Dimensionen von rechten und linken Ventrikel sowie beider Vorhöfe, der systolischen und diastolischen linksventrikulären Funktion, der Morphologie der Herzklappen sowie der pulmonalarteriellen Drücke. Die Patientenkohorte wurde zusätzlich in Subgruppen nach Symptomatik, nach additiven chirurgischen Interventionen und nach dem Vorliegen von chronischem Vorhofflimmern analysiert. Die Ergebnisse der Mitralklappenrekonstruktion zeigten erwartungsgemäß postoperativ eine signifikante Reduktion des Schweregrades der Mitralklappenregurgitation, eine Verkleinerung der linksseitigen Herzhöhlen, eine Normalisierung der linksventrikulären Pumpfunktion und der pulmonalarteriellen Drücke. Asymptomatische Patienten im Sinusrhythmus mit isolierter Mitralklappenrekonstruktion hatten die günstigsten postoperativen echokardiographischen Ergebnisse. Weiterhin war eine postoperativ eingeschränkte rechtsventrikuläre und linksventrikuläre diastolische Funktion zu postulieren. Ein mit fast 20% beträchtlicher Anteil der Patienten mit einer postoperativen Vena contracta der Mitralklappenregurgitation ≥ 3mm war vermutlich auf eine Vorselektion der Patienten zurückzuführen. Schlussfolgernd sollte eine Mitralklappenrekonstruktion möglichst vor Eintreten irreversibler kardialer Schädigungen durchgeführt werden.

Performance of air operated valves is a major maintenance concern in process industries. Anecdotal information indicates that reliability of some high maintenance valves has been improved by using an ion deposition process to achieve engineered surfaces on selected components. This project compared friction for various surface treatments of selected valve components. Results indicate valve performance may be slightly more consistent when an engineered surface is applied in the valve packing area; however surface treatment in this area does not appear to have a dominant affect on reducing valve friction. Results indicate a linear relation between stem friction and torque applied to packing flange nuts, and even after a valve is in service, controlled packing adjustments can be made without significantly changing valve stroke time.

AB SOMAS Ventiler manufactures valves for different applications. A valve of type DN VSSL 400, PN 100, used in high-temperature and high-pressure applications was investigated in this thesis. This type of valve is coated with high cobalt alloys to achieve the tribological properties needed for this severe condition. However there is a request from AB Somas Ventiler to find another solution. This request is based on the fact that demands on higher temperatures, from customers, yields higher requirements on the material. It is also a price issue since cobalt is quite expensive. Materials investigated were high-nitrogen steel, Vanax 75, nickel-based superalloy Inconel 718 and hardened steels, EN 1.4903 and EN 1.4923 presently used as base material in the valve. Calculation of contact pressure that arises when the valve is closed was first approached by using finite element method (FEM). Several models were constructed to show the behavior of the valve during closing in terms of deformation. Hot wear tests, in which a specimen was pressed against a rotating cylinder, were performed to be able to compare the materials to the solution of today and among each other. Data extracted from the tests were compiled in the form of coefficients of friction. Profilometer examinations were used to reveal the volumes of worn and adhered material and together with scanning electron microscopy (SEM) the wear situation for each material couple could be assessed. Wear mechanisms detected in SEM were adhesive and abrasive and the results clearly showed that the steels were not a good solution because of severe adhesive wear due to the similarity of mating materials creating a more efficient bonding between the asperities. Vanax 75 showed much better performance but there was still an obvious difference between the steels and the superalloy in terms of both coefficient of friction and amount of wear. On this basis, Inconel 718 was selected as the most suitable material to replace the high cobalt alloys used in the valves today. / AB Somas ventiler är ett företag som tillverkar ventiler för ett brett spann av applikationer. I det här examensarbetet har undersökningar genomförts på en ventil av modell DN VSSL 400, PN 100, som normalt används i applikationer för höga tryck och höga temperaturer. Ventilen beläggs i dagsläget med höghaltiga koboltlegeringar för att uppnå de tribologiska egenskaper som krävs i de påfrestande arbetsförhållanden som råder. AB Somas Ventiler har dock framfört en förfrågan om att hitta en alternativ lösning, en förfrågan som grundar sig i att kundernas ständiga önskemål på att ventilerna ska klara högre arbetstemperaturer också medför högre krav på ventilmaterialen. Det är även en prisfråga, då kobolt är en dyr legering att använda sig av. De material som inkluderades i undersökningen var det kvävelegerade stålet Vanax 75, nickelbaserade superlegeringen Inconel 718 samt de två stålen EN 1.4903 och EN 1.4923 i härdat tillstånd. De två sistnämnda används idag som basmaterial i ventilen. Genom att använda den finita element metoden (FEM) kunde en första beräkning göras av det kontakttryck som uppstår då ventilen stängs. Flera modeller konstruerades för att simulera ventilens deformation vid stängning. Där efter utfördes nötningstester i hög temperatur på de alternativa materialen, genom att låta en provbit pressas mot en roterande cylinder, för att sedan kunna göra en jämförelse mellan materialen och även med den nuvarande lösningen. Från nötningstesterna erhölls data som kunde användas för att ta fram friktionskoefficienter för de olika materialparen. Med hjälp av undersökningar med profilometer och svepelektronmikroskop (SEM) kunde värden på nötta och vidhäfta volymer erhållas tillsammans med information om nötningssituationer för ytorna mellan de olika materialparen. De nötningsmekanismer som påvisades med hjälp av SEM-undersökningen var adhesiv och abrasiv nötning, och resultaten visade tydligt att nötningen av stålen var omfattande, på grund av att lika material i kontakt med varandra skapar starkare band mellan ytorna, och att de därför inte var en intressant lösning. Det kvävelegerade Vanax 75 uppförde sig visserligen bättre men en tydlig skillnad mot superlegeringarna kunde dock fortfarande konstateras, sett till både friktionskoefficient och mängden slitage. Baserat på dessa resultat valdes Inconel 718 som det bäst lämpade materialet att ersätta de höghaltiga koboltlegeringarna som idag används i ventilen.

Venous valves (VVs) are critical for unidirectional blood flow from superficial and deep veins towards the heart. Congenital valve aplasia or agenesis may, in some cases, be a direct cause of vascular disease, motivating an understanding of the molecular mechanisms underlying the development and maintenance of VVs. Three gap junction proteins (Connexins), Cx37, Cx43, and Cx47, are specifically expressed at VVs in a highly polarized fashion. VVs are absent from adult mice lacking Cx37; however it is not known if Cx37 is required for the initial formation of valves. In addition, the requirement of Cx43 and Cx47 for VV development has not been studied. Here, we provide a detailed description of Cx37, Cx43, and Cx47 expression during mouse vein development and show by gene knockout that each Cx is necessary for normal valve development. The valve phenotypes in the knockout lines exhibit Cx-specific differences, however, including whether peripheral or central VVs are affected by gene inactivation. In addition, we show that a Cx47 null mutation impairs peripheral VV development but does not affect lymphatic valve formation, a finding of significance for understanding how some CX47 mutations cause inherited lymphedema in humans. Finally, we demonstrate a striking segregation of Foxc2 and NFATc1 transcription factor expression between the downstream and upstream faces, respectively, of developing VV leaflets and show that this segregation is closely associated with the highly polarized expression of Cx37, Cx43, and Cx47. The partition of Foxc2 and NFATc1 expression at VV leaflets makes it unlikely that these factors directly cooperate during the leaflet elongation stage of VV development. (C) 2016 Elsevier Inc. All rights reserved.