Submitted in fulfilment of the Master’s Degree in Clinical Technology, Durban University of Technology, 2012. / The sirolimus-eluting stent (Cypher) was the first approved drug- eluting stent by the Food and Drug Administration in April 2003. This is a stent that is based on a bare-metal stent and is coated with a layer of polymer incorporating sirolimus and releasing it by diffusion. Drug-eluting stents reduced risk of restenosis and repeat revascularization as compared with bare-metal stents. Clinical data has raised concerns that drug-eluting stents are associated with late untoward events. Objectives: The objective of this study was to test the hypothesis that stenting is safe and effective treatment for coronary artery disease. Methods and Results: Sirolimus-eluting stenting was performed in 30 patients with 34 coronary lesions. Detailed clinical follow-up data was collected by personal interview or telephone contact at 1, 6, 12 and 24 months. Patients were followed for 2 years for the occurrence of angina and cardiovascular events namely death, myocardial infarction, stent thrombosis and target lesion revascularization. The mean age of the cohort was 62.33±10.99 years; 83 percent were male, 6 percent were diabetic, 53 percent had hypertension. In spite of the overall patient and lesion complexity there were no incidences of major adverse cardiac events and all patients remained angina free out to two years. Dual antiplatelet therapy with aspirin and plavix varied from at least four weeks to one year. One patient had a bleeding event. Conclusions: Treatment of lesions with sirolimus-eluting stents is associated with a sustained clinical benefit two years after device implantation.

The success of endoluminal stent-graft treatment for abdominal aortic aneurysm relies on maintenance of an effective seal when the stent expands into the healthy artery. Clinical observation of aortic neck dilation following endoluminal grafting has led to the hypothesis that excessive stent expansion forces may cause remodelling and dilation of the artery to accommodate the strong forces. This may lead to failure of the seal, hence so-called endoleak. In this research, we analysed the force field generated by aortic stent-grafts and investigated in vitro approaches for studying the effects of these forces on cells within the vascular wall. The pressure-deformation behaviour of ovine arteries was examined experimentally and was found to vary with artery type. A finite element model of abdominal aorta (AA) characterised by Mooney-Rivlin hyperelastic material properties was validated. The property inputs were derived from the polynomial form of the strain energy density function proposed by Patel and Vaishnav. Stent-artery contact simulations revealed stresses 1.2-19 times higher than within a normal vessel at 120 mmHg when contacted by a zig-zag, square cross-section stent that expanded the AA by 3-16%. Streses 1.3-23 times normal were predicted for circular cross-section stents at the same range of expansions. The stress distribution was determined to be concentrated at the contacting surface and within the inner region of the aortic wall. These results confirmed that the forces within the vessel wall are likely to place unnatural physiological demands on the cells within. We then developed an in vitro system for studying the impact of this mechanical stress on cells within a three dimensional (3D) structure. A 20 wt% poly(vinyl alcohol) (PVA) - 5 wt% collagen tubular construct was developed to support cells, and was shown to sustain physiological blood pressures. Two cell-seeding techniques were examined, direct cell encapsulation and surface cell-seeding. Both demonstrated the capability of entrapping viable cells within the construct that remained viable for up to 4 days. In conclusion, stent contact does create abnormal stress concentrations within the vessel wall with a magnitude severely higher than physiological levels. A feasible tubular construct and an in vitro system were developed, enabling further assessments on the effects of these abnormality on the cells.

Thesis (M.S.)--University of Alabama at Birmingham, 2007. / Title from PDF of title page (viewed October 13, 2009). Additional advisors: Brigitta C. Brott, Jack E. Lemons, Steven G. Lloyd. Includes bibliographical references (p. 28-31).

Thesis (M.S.)--Duquesne University, 2007. / Title from document title page. Abstract included in electronic submission form. Includes bibliographical references (p. 48-51) and index.

Thesis (M.S.)--University of Alabama at Birmingham, 2006. / Description based on contents viewed June 25, 2007; title from title screen. Includes bibliographical references (p. 41-42).

Thesis (M.S.)--University of Alabama at Birmingham, 2007. / Additional advisors: Peter G. Anderson, Brigitta C. Brott, Jack E. Lemons. Description based on contents viewed Feb. 4, 2008; title from title screen. Includes bibliographical references (p. 69-70).

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2009. / Title from title screen (site viewed February 25, 2010). PDF text: 1 v. (ca. 280 p. : ill.). UMI publication number: AAT 3386755. Includes bibliographical references. Also available in microfilm and microfiche formats.

Thesis (MScEng (Mechanical and Mechatronic Engineering))--University of Stellenbosch, 2009. / Elderly patients suffering from aortic valvular dysfunction are often denied aortic valve replacement due to the fact that they are classified as too old and fragile to handle the physical stress of open-heart surgery and cardio-pulmonary bypass. There exists a need for an alternative solution which places less physical stress on the body. The development of a percutaneous aortic heart valve (PAHV), which may be implanted through a minimally invasive procedure, will provide a solution to old and fragile patients who otherwise have a very limited life expectancy. The development of such a device entails a costly and time-consuming process which involves a number of phases, including a prototype development phase, an in-vitro testing phase, an animal trial phase and a human trial phase. This thesis focuses on the design and analysis of the stent component for a PAHV, suitable for implantation in sheep (animal trial phase). The process of developing a first prototype, involved an analysis of the stent design requirements. This analysis was followed by a concept generation phase as well as comprehensive finite element (FE) analyses of the most promising concepts. The objective of the FE analyses was to determine the effects of a variation in strut width on the performance characteristics of the concepts. Based on the results of the FE analyses, final geometries were selected for each of the two most promising concepts. Subsequent to the selection of the final geometries, a number of prototypes were manufactured. The prototypes were subjected to an electro-polishing process. An experimental analysis was also conducted on the prototypes to evaluate the accuracy of the (FE) simulations as well as the actual performance of the stent prototypes. The results of the FE analyses and experimental analyses indicated that strut width had a substantial influence on the parameters that were defined to characterise stent performance. The results of the analyses also highlighted the advantages and disadvantages of each concept and aided in identifying the concept that would be most suitable for the required application. Limitations of the study were identified and recommendations were made to assist the continued research and development of the device.

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Stenting remains a common treatment option for atherosclerotic arteries. The main drawback of early stent platforms was restenosis, which has been combated by drug eluting stents; however, these stents have suffered from a higher incidence of late stage thrombosis. To address current stenting limitations, the major research focuses have been the development of the next generation of drug eluting stents and first generation bioabsorbable stents. The main objective of this dissertation was the design and development of a new class of bioabsorbable stent composed of elastin mimetic protein polymers. The first phase explored different stent design schemes and fabrication strategies. Successfully fabricated stents were then mechanically tested to ensure they possessed sufficient mechanical strength. Additionally, described herein is the potential to modulate the properties of the elastin mimetics through different crosslinking strategies. We have demonstrated that chemical crosslinking allows for the tailoring of the physical, mechanical, drug delivery, and endothelialization properties of these materials. The potential for drug delivery from this elastin mimetic stent was benchmarked as was the potential to endothelialize these stents. Furthermore, we developed the necessary delivery systems to allow for deployment in the rat aorta model.