Houman Zahedmanesh

Simulation of a balloon expandable stent in a realistic coronary artery; Determination of the optimum modelling strategy

Computational models of stent deployment in arteries have been widely used to shed light on various aspects of stent design and optimisation. In this context, modelling of balloon expandable stents has proved challenging due to the complex mechanics of balloon-stent interaction and the difficulties involved in creating folded balloon geometries. In this study, a method to create a folded balloon model is presented and utilised to numerically model the accurate deployment of a stent in a realistic geometry of an atherosclerotic human coronary artery. Stent deployment is, however, commonly modelled by applying an increasing pressure to the stent, thereby neglecting the balloon. This method is compared to the realistic balloon expansion simulation to fully elucidate the limitations of this procedure. The results illustrate that inclusion of a realistic balloon model is essential for accurate modelling of stent deformation and stent stresses. An alternative balloon simulation procedure is presented however, which overcomes many of the limitations of the applied pressure approach by using elements which restrain the stent as the desired diameter is achieved. This study shows that direct application of pressure to the stent inner surface may be used as an optimal modelling strategy to estimate the stresses in the vessel wall using these restraining elements and hence offer a very efficient alternative approach to numerically modelling stent deployment within complex arterial geometries. The method is limited however, in that it can only predict final stresses in the stented vessel and not those occurring during stent expansion, in which case the balloon expansion model is required.

Determination of the influence of stent strut thickness using the finite element method: implications for vascular injury and in-stent restenosis

Many clinical studies, including the ISAR-STEREO trial, have identified stent strut thickness as an independent predictor of in-stent restenosis where thinner struts result in lower restenosis than thicker struts. The aim of this study was to more conclusively identify the mechanical stimulus for in-stent restenosis using results from such clinical trials as the ISAR-STEREO trial. The mechanical environment in arteries stented with thin and thicker strut stents was investigated using numerical modelling techniques. Finite element models of the stents used in the ISAR-STEREO clinical trial were developed and the stents were deployed in idealised stenosed vessel geometries in order to compare the mechanical environment of the vessel for each stent. The stresses induced within the stented vessels by these stents were compared to determine the level of vascular injury caused to the artery by the stents with different strut thickness. The study found that when both stents were expanded to achieve the same initial maximum stent diameter that the thinner strut stent recoiled to a greater extent resulting in lower luminal gain but also lower stresses in the vessel wall, which is hypothesised to be responsible for the lower restenosis outcome. This study supports the hypothesis that arteries develop restenosis in response to injury, where high vessel stresses are a good measure of that injury. This study points to a critical stress level in arteries, above which an aggressive healing response leads to in-stent restenosis in stented vessels. Stents can be designed to reduce stresses in this range in arteries using preclinical tools such as numerical modelling.

Bacterial cellulose as a potential vascular graft: Mechanical characterization and constitutive model development

Bacterial cellulose (BC) is a polysaccharide produced by Acetobacter Xylinum bacteria with interesting properties for arterial grafting and vascular tissue engineering including high-burst pressure, high-water content, high crystallinity, and an ultrafine highly pure fibrous structure similar to that of collagen. Given that compliance mismatch is one of the main factors contributing to the development of intimal hyperplasia in vascular replacement conduits, an in depth investigation of support mechanical properties of BC is required to further supporting its use in cardiovascular-grafting applications. The aim of this study was to mechanically characterize BC and also study its potential to accommodate vascular cells. To achieve these aims, inflation tests and uniaxial tensile tests were carried out on BC samples. In addition, dynamic compliance tests were conducted on BC tubes, and the results were compared to that of arteries, saphenous vein, expanded polytetrafluoroethylene, and Dacron grafts. BC tubes exhibited a compliance response similar to human saphenous vein with a mean compliance value of 4.27 × 10(-2) % per millimeter of mercury over the pressure range of 30-120 mmHg. In addition, bovine smooth muscle cells and endothelial cells were cultured on BC samples, and histology and fluorescent imaging analysis were carried out showing good adherence and biocompatibility. Finally, a method to predict the mechanical behavior of BC grafts in situ was established, whereby a constitutive model for BC was determined and used to model the BC tubes under inflation using finite element analysis.

A multiscale mechanobiological modelling framework using agent-based models and finite element analysis: application to vascular tissue engineering

Computational models of mechanobiological systems have been widely used to provide insight into these systems and also to predict their behaviour. In this context, vascular tissue engineering benefits from further attention given the challenges involved in developing functional low calibre vascular grafts with long-term patency. In this study, a novel multiscale mechanobiological modelling framework is presented, which takes advantage of lattice-free agent-based models coupled with the finite element method to investigate the dynamics of VSMC growth in vascular tissue engineering scaffolds. The results illustrate the ability of the mechanobiological modelling approach to capture complex multiscale mechanobiological phenomena. Specifically, the framework enabled the study of the influence of scaffold compliance and loading regime in regulating the growth of VSMCs in vascular scaffolds and their role in development of intimal hyperplasia (IH). The model demonstrates that low scaffold compliance compared to host arteries leads to increased luminal ingrowth and IH development. In addition, culture of a tissue-engineered blood vessel under a pulsatile luminal pressure reduced luminal ingrowth and enhanced collagen synthesis within the scaffold compared to non-pulsatile culture. The mechanobiological framework presented provides a robust platform for testing hypotheses in vascular tissue engineering and lends itself to use as an optimisation design tool.

A method to develop mock arteries suitable for cell seeding and in-vitro cell culture experiments

Sylgard((R)) is a biocompatible elastomer which has been widely used in biomedical applications including in simulations of the mechanical response of soft tissues and mechanotransduction investigations. In this study the effect of fabrication parameters including base to curing agent ratio and curing time on the mechanical response of Sylgard((R)) was investigated and a novel fabrication technique for the production of mock arteries with highly uniform thickness, which is essential for mechanotransduction studies, is described. Finally a method for the surface treatment of Sylgard((R)) using sulphuric acid and fibronectin to enhance smooth muscle cell (SMC) adhesion is proposed and examined in vitro. Sylgard((R)) mock coronary arteries fabricated using the proposed technique exhibited a mechanical response close to arterial tissue with cell adhesion enhanced using the surface treatment techniques described.

Numerical analysis of airgap stability under process-induced thermo-mechanical loads

In order to understand the state of process induced stresses in air-gap interconnect structures fabricated by means of etch-back procedure, finite element (FE) models of a 90nm pitch interconnect were developed and stress analysis of the structure was conducted as a function of the dielectric liner and metal barrier (MB) thicknesses in a parametric study in order to minimize the risk of mechanical failure. The results identified the sidewall dielectric liner as the critical location where high stresses can result in failure of structures under thermo-mechanical loads. Simulations suggest that optimal mechanical stability is achieved by minimizing the MB thickness and maximizing the thickness of the conformal dielectric liner. The upper limit of the liner thickness however, is dictated by restrictions imposed by interline capacitance which can lead to RC delay.

Vascular Stent Design Optimisation Using Numerical Modelling Techniques

Since their first introduction in 1985 by Palmaz et al. (1985), balloon-mounted vascular stents have revolutionised the treatment of atherosclerosis, and in particular coronary artery disease. Vascular stents were developed to restore blood flow in stenosed arteries of the body, thereby preventing ischemia and myocardial infarction in peripheral and coronary arteries, respectively. A modification to these first stents by Schatz et al. (1987) led to the development of the first commercially successful stent, the Palmaz–Schatz stent. This redesign of the very first stent led the way in a new era of vascular medical device design, with a vast range of new stent designs, materials and adjunct drug therapies subsequently emerging at an ever increasing pace. Now over 25 years on, stents have undeniably become the gold standard in the non invasive treatment of atherosclerosis with 3 million implanted worldwide each year (van Beusekom & Serruys, 2010). To-date, vascular stents have been developed using an extensive range of high grade metals, from tantalum and titanium to the more common medical grade stainless steel, and more recently high yield strength materials such as cobalt chromium and platinum chromium alloys have also been used (Lally et al., 2006; Gopinath et al., 2007; Huibregtse et al., 2011). Self-expanding stents have been developed from shape memory alloys for peripheral anatomies to eliminate the need for expansion using angioplasty balloons (Gopinath et al., 2007). Biodegradable stents have been developed to allow for removal of the stent following successful revascularisation, whilst stents have also been developed to incorporate complementary drug, gene and radiation therapies and even pre-seeded with endothelial cells to lower thrombosis and encourage re-endothelialisation (Serruys et al., 2006; Sharif et al., 2004; Kay et al., 2001; Van der Giessen 1988; Dichek et al., 1989).While many of these new stent designs have offered improvements on their predecessors, no single design has successfully incorporated all of the characteristics of the ideal stent and one significant limitation in the long-term success of stents still remains, namely in-stent restenosis.

Airgaps in nano-interconnects: Mechanics and impact on electromigration

In this study, electromigration (EM) of interconnects (90 nm pitch) with airgaps was investigated using a combination of computational mechanics, analytical modelling, and EM experiments. EM experiments reveal that airgapped Cu lines without dielectric liner (non-capsulated) fail early by voiding in the EM tests due to oxidation and deterioration of interfacial adhesion at Cu interfaces. Also at high temperature regimes, extrusive failures under thermal compressive stresses were observed in airgapped Cu lines without dielectric liner. Therefore, Cu encapsulation using a conformal dielectric liner of adequate thickness is necessary in order to ensure hermeticity and provide endurance to the thermal and EM induced extrusive stresses. For an airgapped interconnect with a hermetic 5 nm PECVD conformal carbon doped silicon nitride (SiCN) liner deposited at 370 °C, a (jL)crit comparable to that of non-airgapped interconnects (with ultra-low-k dielectric 2.5 inter-layer dielectric) was predicted by the simulatio...

Numerical simulation of nano-indentation induced fracture of low-k dielectric thin films using the cube corner indenter

In this study, indentation and fracture of compliant low-dielectric constant (low-k) films on silicon substrates was investigated by means of finite element (FE) modelling. Cohesive zone damage models were employed for fracture simulation and damage constitutive parameters and plastic yield stress of organosilicate glass 2.4 (OSG 2.4) low-k films coated on silicon substrates were obtained by correlating the force-displacement and crack growth response with experiments. The model lends itself to characterization of brittle films where the value of the Youngs modulus, the maximum cohesive strength, the critical cohesive energy release rate and plastic yield stress of the low-k films can be extracted only by conducting cube corner indentation experiments and employing the finite element model.

Thermal expansion coefficients of ultralow-k dielectric films by cube corner indentation tests at elevated temperatures

This paper demonstrates the use of cube corner indentation tests performed at elevated temperatures to measure the coefficient of thermal expansion (CTE) of ultralow-k dielectric films. Using this approach, the CTE of organo-silicate glass low-k films with different intrinsic film stresses is estimated to vary between 8.2 ± 0.8 ppm/ °C and 10.9 ± 1.1 ppm/ °C. The advantages and limitations of the proposed test methodology are discussed.