Minimally invasive vascular interventions with stent deployment have become a popular alternative to conventional open surgery in the treatment of many vascular disorders. However, the high initial success rates of endovascular repairs have been overshadowed by reported complications that cause re-interventions and, in the worst case, morbidity and mortality. The dangerous complications could be mitigated by better choice of device design and by the appropriate positioning of the implant inside the vessel. However, there is currently no possibility for the interventionist to predict the resulting position and the expanded shape of the device for a given patient, before the actual procedure, within the clinical setting. Motivated by this unmet clinical need and the lack of suitable methods, this thesis develops a methodology for modelling virtual deployment of implantable devices inside patient vessels, that features fast computational execution times and can be used in clinical practice. This novel deployment method was developed based on a spring-mass model and was tested in different deployment scenarios, expanding stents inside vessels in the order of seconds. Further, the performance of the novel method was optimised by calibrating a set of parameters with the help of a genetic algorithm, which utilises the outcomes of a finite element analysis as a learning reference. After the calibration, the developed stenting method demonstrated acceptable accuracy as compared to the "gold standard" of the finite element simulation. Finally, on a real patient case, 4 alternative stenting scenarios were investigated by comparing the subsequent blood flow conditions, via computational haemodynamics. The obtained results suggested that device design, dimensions, stiffness and positioning have important implications on the post-procedural haemodynamics of the vessel. Ultimately, the presented results can play a transformative role in aiding clinical decision-making and also give rise to overall improvements in implant design and deployment procedure.

Die retrospektive Arbeit untersucht die in der Zeit von Januar 1993 bis Oktober 2002 an der Uniklinik Würzburg implantierten 294 aortodistalen Gefäßprothesen. Dabei erfolgte sowohl eine Auswertung der perioperativen Komplikationen als auch der Langzeitergebnisse. Mit Hilfe von Chi-Quadrat Tests und Kaplan-Meier Berechnungen konnte ein direkter Einfluss unterschiedlicher Faktoren auf die Ergebnisse nachgewiesen werden. In der Diskussion wurden die Ergebnisse internationalen Publikationen gegenübergestellt und mit alternativen Therapiemethoden verglichen. Zusammenfassend lässt sich die aortobifemorale Y-Prothese bei Patienten mit zufriedenstellendem Allgemeinzustand und einer proximal manifestierten pAVK angesichts eines durch andere Verfahren nicht erreichten Risiko-Nutzen Verhältnisses nach wie vor als Goldstandard empfehlen. / This retrospective work examines all 294 aortodistal grafts which were implantated by the surgical section of the university hospital Würzburg from the time of january 1993 till october 2002. Perioperative complications were as well in the centre of interest as longterm results. Chi-Quadrat-Tests and Kaplan-Meier-Statistics showed direct influence of several factors on the results. In the discussion the results were opposed to international publications and compared to alternative treatments. In conclusion the aortobifemoral graft in patients with satisfying general conditions and a proximal manifested pAOD due to the, by other methods never achieved, risk-benefit-ratio can still be adviced as the goldstandard.

Duas técnicas invasivas para o tratamento da doença aterosclerótica coronariana oclusiva firmaram-se ao longo dos anos: revascularização cirúrgica do miocárdio e angioplastia transcutânea com stents metálicos. O estudo visa comparar as alterações histopatológicas causadas por stents metálicos coronarianos fabricados com a superliga de composição química em porcentagem em peso cromo 20%, tungstênio 15%, níquel 10% e cobalto restante, designada ASTM F.90, revestidos, ou não, com carbeto de silício pelo processo de asperção térmica originando uma superfície hidrofílica. Stents com espessura das hastes entre 80 a 90 nm, área das células entre 1,4 a 2,1 mm² e relação metal-artéria de 13 a 19%, em pacientes reestenosantes que sofreram posteriormente revascularização cirúrgica do miocárdio, com aqueles não submetidos à angioplastia prévia. Foram determinados dois grupos: grupo I ou grupo controle, pacientes que sofreram revascularização cirúrgica do miocárdio sem angioplastia prévia de qualquer natureza; grupo II pacientes submetidos à revascularização cirúrgica do miocárdio, após reestenose intra-stent coronariana. Pacientes de ambos os grupos foram avaliados rotineiramente quanto à indicação e risco cirúrgico e durante o procedimento convencional da revascularização cirúrgica do miocárdio utilizando circulação extracorpórea, antes de realizar a anastomose do enxerto vascular na coronária, amostras contendo pequenos fragmentos de endotélio foram retiradas juntamente com fragmentos dos stents, enviadas para análise histopatológica e produção de laminas coradas com H-E. Observou-se a presença de arterite crônica caracterizada por infiltrado mononuclear em conjunto com fenômeno de proliferação fibroblástica e de musculatura lisa naqueles pacientes que apresentavam reestenose intra-stent, sendo mais intenso no local do stent. A visualização das superfícies dos stents em escala nanometrica (MFA) é de suma importância para análise estrutural das próteses, avaliando irregularidades nas superfícies recobertas das hastes dos stents. A persistência de arterite crônica coronariana avaliada por infiltrado linfomononuclear e proliferação de fibrocolágeno foi constatada em pacientes reestenosantes. / Two invasive techniques for the treatment of occlusive coronary atherosclerosis disease were signed over the years: coronary artery bypass surgery and transcutaneous angioplasty with bare metal stent. The study attempts to compare the histopathological abnormality caused in patients with implantation of bare metal stent in coronary made with: Chromium 20%, Tungsten 15%, Nickel 10% and Cobalt remainder, ASTM F.90 alloy for surgical implant applications, and covered with a thin layer of amorphous silicon carbide, or not, and its total or partial obstruction, after undergoing coronary artery bypass grafting, with those who had coronary artery bypass surgery with no previous angioplasty. Two groups were studied: group I, or control group, patients who underwent coronary artery bypass grafting without previous angioplasty of any kind; group II of patients undergoing coronary artery bypass surgery after coronary-stent restenosis. Patients in both groups were evaluated for the indication and surgical risk; was done routinely during the procedure of conventional coronary artery bypass grafting with cardiopulmonary bypass. Before performing the anastomosis in coronary vascular graft, a small fragment of the endothelium was removed along whit a fragment of the stent, and sent for analysis with hematoxilin-eosin. The presence of chronic inflammatory coronary reaction was detected, mediated by mononuclear cells with phenomenon of fibroblast and smooth muscle proliferation in patients presenting in-stent restenosis. It w coronary reaction as also observed that the inflammatory and proliferative process is more intense at the site of stent implantation. The analysis of surface of the stents used atomic force microscopy proved to be an important method for the surface analysis for stents, and showed on nanometric scale an irregular coverage of silicon carbide. In conclusion, in the patients with restenosis in-stent occurs persistence of chronic inflammation with mononuclear cells and process of fibroblast proliferation.

Aim: To describe innovative uses of catheter based treatment in a variety of native and post surgical stenoses in children and young adults with congenital heart disease. Background: Cardiac catheterization in man was first described 1929 and since then there has been a drive to develop endovascular techniques to investigate and treat both congenital and acquired heart disease. Many of the advances are being made in congenital heart disease. Methods: A number of congenital cardiac stenotic lesions were studied including baffle obstruction after atrial switch for transposition of the great arteries, aortic stenosis in infants, coarctation of the aorta, peripheral pulmonary artery stenosis and superior vena caval obstruction. The use of angioplasty balloons, cutting balloons, stents and alternative catheter approaches were investigated for these lesions. Results: Following atrial redirection surgery for transposition of the great arteries balloon angioplasty improved baffle haemodynamics. The technique of anterograde balloon dilation of the aortic valve was developed and had superior outcomes in terms of aortic insufficiency compared to a retrograde approach in neonates with severe aortic valve stenosis. In an animal model of peripheral pulmonary arterial stenosis, the application of cutting balloon angioplasty produced effective relief in a controlled fashion. Balloon mounted stents were used in patients with native and post surgical coarctation of the aorta with significant relief of stenosis and relief of hypertension. Finally, a group of patients with superior vena obstruction syndrome after surgical repair of partial anomalous pulmonary venous drainage had successful treatment using balloon mounted stents. Conclusions: Catheter based treatment of congenital and post surgical vascular stenoses of the heart and great arteries using angioplasty balloons, cutting balloons and balloon mounted stents is safe and appears to be effective in the short and medium term. It may represent a useful alternative to surgery and will reduce the number of surgical procedures required over a lifetime. Future directions will include bio-absorbable stents and hybrid techniques involving surgery.

"Cellulose nanocrystals, one of the most abundant materials in nature, have attracted great attention in the biomedical community due to qualities such as supreme mechanical properties, biodegradability, biocompatibility and low density. In this research, we are interested in developing a bio-inspired material-by-design approach for cellulose-based composites with tailored interfaces and programmed microstructures that could provide an outstanding strength-to-weight ratio. After a preliminary study on some of the existing biomaterials, we have focused our research on studying the nanostructure and nanomechanics of the bamboo fiber, a cellulose-based biocomposite, designed by nature with remarkable strength-to-weight ratio (higher than steel and concrete). We have utilized atomistic simulations to investigate the mechanical properties and mechanisms of interactions between cellulose nanofibrils and the bamboo fiber matrix which is an intertwined hemicellulose and lignin called lignin-carbohydrate complex (LCC). Our results suggest that the molecular origin of the rigidity of bamboo fibers comes from the carbon-carbon or carbon-oxygen covalent bonds in the main chain of cellulose. In the matrix of bamboo fiber, hemicellulose exhibits larger elastic modulus and glass transition temperature than lignin whereas lignin shows greater tendency to adhere to cellulose nanofibrils. Consequently, the role of hemicellulose is found to enhance the thermodynamic properties and transverse rigidity of the matrix by forming dense hydrogen bond networks, and lignin is found to provide the strength of bamboo fibers by creating strong van der Waals forces between nanofibrils and the matrix. Our results show that the amorphous region of cellulose nanofibrils is the weakest interface in bamboo microfibrils. We also found out that water molecules enhance the mechanical properties of lignin (up to 10%) by filling voids in the system and creating hydrogen bond bridges between polymer chains. For hemicellulose, however, the effect is always regressive due to the destructive effect of water molecules on the hydrogen bond in hemicellulose dense structure. Therefore, the porous structure of lignin supports the matrix to have higher rigidity in the presence of water molecules. "

Le traitement endovasculaire des anévrismes de l’aorte (Endovascular Aneurysm Repair ou EVAR) est une chirurgie mini-invasive qui consiste à faire glisser une endoprothèse par voie fémorale jusqu’au niveau de l’anévrisme afin de re-canaliser le flux sanguin. Les principales complications qui peuvent survenir sont les phénomènes de migration et d’endofuites (écoulement persistant de sang dans le sac anévrismal) de type Ia. Ces phénomènes apparaissent lorsque l’étanchéité n’est plus assurée entre l’extrémité proximale de l’endoprothèse et le vaisseau sanguin. Dans ce travail, des simulations paramétrées de déploiement complet d’un système de pose de stent ont été développées en utilisant la Méthode des Éléments Finis (FEM) afin d’étudier la stabilité du contact lors du largage d’une endoprothèse en nitinol dans un Anévrisme de l’Aorte Thoracique (AAT) réaliste. Les facteurs suivants associés à ces complications ont été étudiés : (1) la longueur de la zone de fixation proximale (PASL), (2) la valeur de surdimensionnement ou « oversizing » du stent (O %), (3) la valeur du coefficient de frottement entre le stent et l’aorte (µ) et (4) l’angulation du collet proximal. L’influence de la présence de calcifications sur le comportement biomécanique de l’endoprothèse lors de son déploiement dans les zones de fixation a également été analysée. Les résultats des simulations ont montré qu’une PASL supérieure à 18 mm est un facteur décisif pour éviter la migration de l’endoprothèse pour une angulation du collet de l’anévrisme de 60° et dans des conditions de contact glissant (µ=0,05). L’augmentation de la valeur de l’oversizing de 10 % à 20 % améliore la résistance de la fixation de la prothèse. En revanche, un oversizing supérieur à 25 % pour une angulation du collet de 60° entraine des déformations excentriques ainsi que la ruine du stent. D’autre part, aucune migration n’a été observée dans un modèle d’aorte idéalisé où l’angulation du collet était de 0°, la PASL de 18 mm et le coefficient de frottement µ de 0,05. Afin d’améliorer le contact et de prévenir l’apparition de phénomènes de migration et d’endofuite de type Ia chez des patients présentant une aorte tortueuse et calcifiée avec un anévrisme fortement angulé, un nouveau design de stent a été proposé, basé sur les résultats des simulations numériques effectuées. La principale difficulté était de trouver un compromis entre flexibilité et raideur. Les résultats des simulations réalisées avec ce nouveau stent ont montré une amélioration de la stabilité de contact, ce qui a pour effet de limiter l’apparition des phénomènes de migration et donc de réduire les complications liées à la procédure endovasculaire. / The main mechanical related problems of endovascular aneurysm repair are migration and endoleak type Ia. They occur when there is no effective seal between the proximal end of stent-graft and the vessel. In this work, we have developed parameterized-deployment simulations of a complete stenting system using finite element method (FEM) to investigate the contact stiffness of a nitinol stent in a realistic Thoracic Aortic Aneurysm (TAA). Therefore, the following factors associated with these complications have evaluated: (1) Proximal Attachment Site Length (PASL), (2) stent Oversizing value (O %), (3) different contact friction situations (stent/aorta) and (4) proximal neck angulation. The calcification impact on the biomechanical behaviour of the deployment at the attachment zone has also been investigated. The simulation results showed that PASL>18mm was a crucial factor to prevent migration at a neck angle of 60⁰and smoothest contact condition (μ=0.05). The increase in (O %) ranging from 10% to 20% improved the fixation strength; however, O % ≥ 25% at 60° caused eccentric deformation and stent collapse. No migration was reported in an idealized aorta model with a neck angle of 0⁰, PASL=18mm and μ=0.05. The numerical observations are used as a guide to optimize the stent design in such neck morphology to strengthen the contact and prevent migration or endoleak type Ia. The optimized stent results showed better contact stability to resist the migration. They also showed a good compromise of stent design requirements (flexibility and stiffness). Moreover, the new design can also prevent the risk of folding or collapse of stent struts by mitigating the energy of eccentric deformation caused by high angulation and oversizing.

Plaque accumulation in the walls of coronary arteries reduces the delivery of nutrients and oxygen to the myocardium. This luminal narrowing can cause clinical indications such as angina or heart attacks, and without treatment, can be fatal. One method of treatment is the percutaneous intervention of stents to re-canalize the vessel. A potential complication of stent implantation is arterial wall remodeling and renarrowing of the vessel; termed restenosis. This can be prevented in the majority of patients with an antiproliferative drug coating on the surface of the stent: a drug-eluting stent. I hypothesize that drug transport in the arterial wall from these devices varies between arterial locations (left anterior descending (LADC) versus right (RC) coronary artery; proximal, middle, versus distal regions). The purpose of this work was to identify the properties of the vascular wall that govern transport, and computationally model stent-based delivery to better understand any differences that could exist in transport based on location. The first aim of this work was to identify the porohyperelastic properties. Permeability showed a decrease along the length of the LADC artery of 198%, and 98.6% along the length of the RC artery (p=NS between LADC and RC). Mechanical properties indicated significant differences between the LADC and RC arteries, with the LADC artery being stiffer than the RC. The second aim of this work was to identify the mass transport and cellular binding properties. There was no difference between the LADC and RC arteries; however, diffusivity peaked in the middle region of both arteries by a factor of 2.07. Convection coupling coefficients indicated an upward trend down each artery with the RC artery having higher values. The third aim was to use the model constants from the previous two aims to create six parametric computational models of stent deployment and drug delivery into the respective arterial sections. Results indicated that RC sections had lower stress along with 2.2 times the species concentration at time points of peak smooth muscle cell migration and remodeling.

No description available.

<p>Covering the metal surface of blood-contacting cardiovascular implants (stents, ventricular assist devices) with functional endothelium may reduce the incidence of clotting and restenosis complications and also reduce the need for risky anticoagulation therapy following implantation of such devices. We developed a novel cell therapy for seeding autologous endothelium onto blood-contacting vascular stents at the point of care to reduce thrombosis and stent restenosis. The proposed research tested the following hypotheses: (1) autologous endothelial cells (ECs) can spread on titanium (Ti) tubes and reduce thrombosis on the Ti surface <italic>in vivo</italic>; (2) shear stresses on the surfaces of an implanted carotid artery stent will be conducive to EC retention and function under arterial flow; and (3) nitinol stents seeded with ECs at the point of care will remain adherent and functional after stent deployment and arterial fluid shear stress conditions <italic>in vitro</italic> and <italic>in vivo</italic>. Based on the experiments reported herein, the primary conclusions of the dissertation are as follows: (1) autologous ECs significantly reduce thrombosis on Ti surfaces implanted into the bloodstream <italic>in vivo</italic>; (2) shear stresses on stent surfaces under carotid artery flow conditions are sufficiently low to be compatible with EC retention and function; (3) ECs seeded onto nitinol stents by infusion at the point of care are retained and spread to form a functional layer following deployment and arterial flow conditions both <italic>in vitro</italic> and <italic>in vivo</italic>.</p> / Dissertation

In the area of translational research, stent developers consult pathologists to obtain the best and most complete amount of data from implanted test devices in the most efficient manner. Through the use of micron-scale computed tomography along with post-fixation staining techniques in this study, full volumes of previously implanted stents have been analyzed in-situ in a non-destructive manner. The increased soft tissue contrast imparted by metal-containing stains allowed for a qualitative analysis of the vessel’s response to the implant with greater sensitivity and specificity while reducing beam-hardening artifact from stent struts. The developed staining techniques included iodine-potassium iodide, phosphomolybdic acid, and phosphotungstic acid, all of which bind to soft tissue and improve image quality through their ability to attenuate high energy X-rays. With these stains, the overall soft tissue contrast increased by up to 85 percent and contrast between medial and neointimal layers of the vessel increased by up to 22 percent. Beam hardening artifact was also reduced by up to 38 percent after staining. Acquiring data from the entirety of the stent and the surrounding tissue increased the quality of stent analysis in multiple ways. The three dimensional data enabled a comprehensive analysis of stent performance, lending information such as neointimal hyperplasia, percent stenosis, delineation of vessel wall layers, stent apposition, and stent fractures. By providing morphological data about stent deployment and host response, this method circumvents the need to make the more traditional histology slides for a morphometric analysis. These same data may also be applied to target regions of interest to ensure histology slides are cut from the optimal locations for a more in-depth analysis. The agents involved in such techniques are readily available in most pathology laboratories, are safe to work with, and allow for rapid processing of tissue. The ability to forego histology altogether or to highly focus what histology is performed on a vessel has the potential to hasten the development process of any coronary stent.