title: Development of pre-clinical models for evaluating performance of self-expanding nitinol stents for peripheral artery applications
Creators: name: Nandan, Swati
Publisher: name: University of Galway
Year: 2024
Subjects: subject: Peripheral Artery Disease
subject: Self-expanding Nitinol Stents
subject: Ex-vivo Theil embalmed cadaveric model
subject: Computational fluid dynamics
subject: Femoropopliteal artery
subject: Spiral Laminar flow stents
subject: Numerical verification of bioreactor
subject: in-vitro biorector
subject: deformation of femoropopliteal stents
subject: Endothelial cell injury response
subject: Image Processing and deformation analysis
subject: Haemodynamic metrics
subject: Pre-clinical models for vascular device testing
subject: Engineering
subject: Biomedical Engineering
subject: FOS: Medical engineering

description: The femoropopliteal artery (FPA) is the most commonly affected site for peripheral artery disease due to its complex biomechanical environment, whereby it experiences extreme loading conditions during limb flexion. This has significant impact on the devices placed in this region and the associated haemodynamics. While self-expanding Nitinol stents are preferred in this region due to their better flexibility, crush recoverability and reduced foreshortening, they have still been associated with restenosis and stent fracture rates as high as 65%. While it is critically important to enhance existing stent designs to improve clinical outcomes, there remains major challenges in this area as complex implanted environment of FPA stents is difficult to faithfully represent ahead of clinical studies. The objective of this thesis was to develop novel pre-clinical models of device performance across in-vitro, ex-vivo and in-silico settings to better understand functional performance and ensure the safety and efficacy of the devices. Firstly, a computationally-informed in-vitro bioreactor system has been designed capable of delivering combination of haemodynamic forces found in native peripheral arteries for endovascular stent device testing upto 4 days. Secondly, an ex-vivo cadaveric model was used to assess the biomechanical performance of two different self-expanding Nitinol stent designs implanted in healthy and calcified legs of Thiel embalmed cadavers. This provided, for the first time, a quantitative approach to investigate the true deformation magnitudes of the FPA stents implanted in Thiel embalmed cadavers upon limb flexion. Finally, in-silico steady state and transient computational fluid dynamics (CFD) models were developed to explore the specific flow characteristics of a novel prototype spiral-flow (SLF) self- expanding Nitinol stent design in straight artery configuration. It was demonstrated that the numerically verified in-vitro bioreactor design captured endothelial (EC) response to self-expanding Nitinol stent deployment subjected to haemodynamic flow conditions comparable to native peripheral arteries for day 1 time point and showed a sustained EC injury response contributing to neointimal growth and development of in-stent restenosis for day 4 time point. Further the developed ex-vivo cadaver model showed true curvature peaks within the ranges of 0.08–0.14 mm- 1 and 0.06–0.18 mm-1 for pre- and post-intervention configurations respectively, during extreme flexed postures of gardening and crossed leg. True flattening peaks within the range of 0.3-0.53 were observed in the pre-intervention configuration for extreme flexed postures while notable peaks in the range of 0.2-0.53 were observed adjacent to stent placement in post-intervention configuration. These peaks of true curvature and flattening were mainly located in adductor hiatus and popliteal regions of the FPA segment suggesting localisation of severe deformations. Interestingly, cadaver leg with calcification and maximum age resulted in maximum bending and notable peaks of flattening deformation in both pre- and post-intervention implying that factors such as presence of calcification, stent placement and age could contribute to increased FPA deformations. It is suggested that the SLF stent design could have lower bending stiffness than control stent providing more flexibility to accommodate severe bending deformations but this required further investigation due to small sample size considered in this thesis. Finally, the developed in-silico CFD models demonstrated that the prototype SLF stent was effective in increasing the wall shear stress in the intra strut region and downstream of the device region improving swirling efficiency, especially at higher Re number. Moreover, SLF stent provided an optimal balance between swirl efficiency and swirl flow propagation downstream. This could make it well-suited for operation within a defined range of Re number and implantation at specific locations in the cardiovascular system. The study demonstrated that the SLF stent effectively eliminated recirculation and separation zones, particularly within the intra-strut region, reducing areas of low time- averaged wall shear stress (TAWSS) and high oscillatory shear index (OSI) typically associated with vascular pathology in the control stent.