Comparison of computational modelling techniques for braided stent analysis.

Braided stents are associated with a number of complications in vivo. Accurate computational modelling of these devices is essential for the design and development of the next generation of these stents. In this study, two commonly utilised methods of computationally modelling filament interaction in braided stents are investigated: the join method and the weave method. Three different braided stent designs are experimentally tested and computationally modelled in both radial and v-block configurations. The results of the study indicate that while both methods are capable of capturing braided stent performance to some degree, the weave method is much more robust.

Comparison of Covered Laser-cut and Braided Respiratory Stents: From Bench to Pre-Clinical Testing.

Lung cancer patients often suffer from severe airway stenosis, the symptoms of which can be relieved by the implantation of stents. Different respiratory stents are commercially available, but the impact of their mechanical performance on tissue responses is not well understood. Two novel laser-cut and hand-braided nitinol stents, partially covered with polycarbonate urethane, were bench tested and implanted in Rhön sheep for 6 weeks. Bench testing highlighted differences in mechanical behavior: the laser-cut stent showed little foreshortening when crimped to a target diameter of 7.5 mm, whereas the braided stent elongated by more than 50%. Testing also revealed that the laser-cut stent generally exerted higher radial resistive and chronic outward forces than the braided stent, but the latter produced significantly higher radial resistive forces at diameters below 9 mm. No migration was observed for either stent type in vivo. In terms of granulation, most stents exerted a low to medium tissue response with only minimal formation of granulation tissue. We have developed a mechanical and in vivo framework to compare the behavior of different stent designs in a large animal model, providing data, which may be employed to improve current stent designs and to achieve better treatment options for lung cancer patients.

Evaluating the interaction of a tracheobronchial stent in an ovine in-vivo model.

Tracheobronchial stents are used to restore patency to stenosed airways. However, these devices are associated with many complications such as stent migration, granulation tissue formation, mucous plugging and stent strut fracture. Of these, granulation tissue formation is the complication that most frequently requires costly secondary interventions. In this study a biomechanical lung modelling framework recently developed by the authors to capture the lung in-vivo stress state under physiological loading is employed in conjunction with ovine pre-clinical stenting results and device experimental data to evaluate the effect of stent interaction on granulation tissue formation. Stenting is simulated using a validated model of a prototype covered laser-cut tracheobronchial stent in a semi-specific biomechanical lung model, and physiological loading is performed. Two computational methods are then used to predict possible granulation tissue formation: the standard method which utilises the increase in maximum principal stress change, and a newly proposed method which compares the change in contact pressure over a respiratory cycle. These computational predictions of granulation tissue formation are then compared to pre-clinical stenting observations after a 6-week implantation period. Experimental results of the pre-clinical stent implantation showed signs of granulation tissue formation both proximally and distally, with a greater proximal reaction. The standard method failed to show a correlation with the experimental results. However, the contact change method showed an apparent correlation with granulation tissue formation. These results suggest that this new method could be used as a tool to improve future device designs.

An ovine in vivo framework for tracheobronchial stent analysis.

Tracheobronchial stents are most commonly used to restore patency to airways stenosed by tumour growth. Currently all tracheobronchial stents are associated with complications such as stent migration, granulation tissue formation, mucous plugging and stent strut fracture. The present work develops a computational framework to evaluate tracheobronchial stent designs in vivo. Pressurised computed tomography is used to create a biomechanical lung model which takes into account the in vivo stress state, global lung deformation and local loading from pressure variation. Stent interaction with the airway is then evaluated for a number of loading conditions including normal breathing, coughing and ventilation. Results of the analysis indicate that three of the major complications associated with tracheobronchial stents can potentially be analysed with this framework, which can be readily applied to the human case. Airway deformation caused by lung motion is shown to have a significant effect on stent mechanical performance, including implications for stent migration, granulation formation and stent fracture.

PulmoStent: In Vitro to In Vivo Evaluation of a Tissue Engineered Endobronchial Stent.

Currently, there is no optimal treatment available for end stage tumour patients with airway stenosis. The PulmoStent concept aims on overcoming current hurdles in airway stenting by combining a nitinol stent with a nutrient-permeable membrane, which prevents tumour ingrowth. Respiratory epithelial cells can be seeded onto the cover to restore mucociliary clearance. In this study, a novel hand-braided dog bone stent was developed, covered with a polycarbonate urethane nonwoven and mechanically tested. Design and manufacturing of stent and cover were improved in an iterative process according to predefined requirements for permeability and mechanical properties and finally tested in a proof of concept animal study in sheep for up to 24 weeks. In each animal two stents were implanted, one of which was cell-seeded by endoscopic spraying in situ. We demonstrated the suitability of this membrane for our concept by glucose transport testing and in vitro culture of respiratory epithelial cells. In the animal study, no migration occurred in any of the twelve stents. There was only mild granulation tissue formation and tissue reaction; no severe mucus plugging was observed. Thus, the PulmoStent concept might be a step forward for palliative treatment of airway stenosis with a biohybrid stent device.

Deformation of the Femoropopliteal Segment: Effect of Stent Length, Location, Flexibility, and Curvature.

PURPOSE: To quantify the deformation behavior of the diseased femoropopliteal segment and assess the change to deformation behavior due to various stent placements. METHODS: The length and curvature changes of 6 femoropopliteal segments (the right and left superficial femoral and popliteal arteries) from 3 cadavers were measured in 3-dimensional space based on rotational angiography image data in straight leg and flexed hip/knee (50°/90°) positions before and after placement of nitinol stents of varying type (EverFlex, Misago, and BioMimics 3D) and length (60, 100, and 200 mm) in different locations along the arteries. Three-dimensional centerline data were extracted for the measurements. RESULTS: All 6 femoropopliteal cadaver segments displayed signs of peripheral artery disease. Hip/knee flexion resulted in vessel shortening and increases in the mean and maximum vessel curvatures in all cases. Location-specific results of the unstented arteries showed that magnitudes of vessel length and curvature change vary as a function of vessel length. The average shortening of the entire femoropopliteal segment due to flexion was observed at 10.7%±0.7%, which was reduced to 8.1%±0.9% after stent deployment. Average and maximum curvatures of the unstented segment increased due to flexion (average: 0.008±0.002 mm-1 to 0.019±0.006 mm-1, maximum: 0.030±0.009 mm-1 to 0.091±0.045 mm-1). After stent deployment, average and maximum curvatures of the flexed stented segments increased compared with the flexed unstented segments (average: 0.019±0.006 mm-1 to 0.022±0.004 mm-1, maximum: 0.091±0.045 mm-1 to 0.103±0.025 mm-1). The most flexurally stiff stent demonstrated the least ability to axially shorten during flexion of the leg at the knee joint. CONCLUSION: The deformation characteristics of the femoropopliteal segment change in the presence of a stent, with the change to the deformation behavior dependent on stent type, stent length, location, flexibility, and intrinsic centerline curvature.

Analysis of Shear-Induced Platelet Aggregation and Breakup.

To better understand the mechanisms leading to the formation of thrombi of hazardous sizes in the bulk of the blood, we have developed a kinetic model of shear-induced platelet aggregation (SIPA). In our model, shear rate regulates a mass-conservative population balance equation which computes the aggregation and disaggregation of platelets in a cluster mass distribution. Aggregation is modeled by the Smoluchowski coagulation equation, and disaggregation is incorporated using the aggregate breakup model of Pandya and Spielman. Previous experimental data for SIPA have been correlated with a special case of this model where only the two-body collision of free platelets was considered. However, the two-body collision theory is oblivious to the steady-state condition, and it required the use of a shear-dependent aggregation efficiency parameter to fit it to experimental data. Our method not only predicts steady states but also correlates with literature data without employing a shear-dependent aggregation efficiency.

A computational analysis of the deformation of the femoropopliteal artery with stenting.

Physiological loads that act on the femoropopliteal artery, in combination with stenting, can lead to uncharacteristic deformations of the stented vessel. The overall goal of this study was to investigate the effect of stent length and stent location on the deformation characteristics of the superficial femoral artery (SFA) using an anatomically accurate, three-dimensional finite element model of the leg. For a range of different stent lengths and locations, the deformation characteristics (length change, curvature change, and axial twist) that result from physiological loading of the SFA along with the mechanical behavior of the vessel tissue are investigated. Results showed that stenting portions of the SFA leads to a change in global deformation characteristics of the vessel. Increased stress and strain values and altered deformation characteristics were observed in the various stented cases of this study, which are compared to previous results of an unstented vessel. The study concludes that shortening, twist and curvature characteristics of the stented vessel are dependent on stent length and stent location within the vessel.

Self-expanding stent modelling and radial force accuracy.

Computational simulations using finite element analysis are a tool commonly used to analyse stent designs, deployment geometries and interactions between stent struts and arterial tissue. Such studies require large computational models and efforts are often made to simplify models in order to reduce computational time while maintaining reasonable accuracy. The objective of the study is focused on computational modelling and specifically aims to investigate how different methods of modelling stent-artery interactions can affect the results, computational time taken and computational size of the model. Various different models, each with increasing levels of complexity, are used to simulate this analysis, representing the many assumptions and simplifications used in other similar studies in order to determine what level of simplification will still allow for an accurate representation of stent radial force and resulting stress concentrations on the inner lining of the vessel during self-expanding stent deployment. The main conclusions of the study are that methods used in stent crimping impact on the resulting predicted radial force of the stent; that accurate representation of stent-artery interactions can only be made when modelling the full length of the stent due to the incorporation of end effects; and that modelling self-contact of the stent struts greatly impacts on the resulting stress concentrations within the stent, but that the effect of this on the unloading behaviour and resulting radial force of the stent is negligible.

Effects of knee flexion on the femoropopliteal artery: a computational study.

During knee flexion, the muscles of the upper leg impose various loads on the underlying femoropopliteal artery resulting in radial compression, bending, torsion, axial extension and axial compression. Measuring the dynamic force environment of the femoropopliteal artery and quantifying its resulting deformation characteristics is an essential input to peripheral device design. The goal of this study was to create an anatomically accurate, three dimensional finite element model capable of capturing the loading conditions and deformation characteristics of the femoropopliteal artery during knee flexion. Three dimensional geometries of the muscle, bone, arterial and soft tissues of the leg were constructed from CT scan data and meshed for finite element analysis. Knee flexion was simulated and deformation characteristics of length change (axial compression), curvature, radial compression and axial twist were quantified and compared to previous experimental studies. The model predicts 8.23% shortening and an average curvature of 0.294±0.26 cm(-1) in the vessel after knee flexion, with maximum stresses of 61.17 kPa and maximum strains of 0.16%. The model created replicates known in vivo deformation characteristics seen previously in angiographic images and for the first time associates femoropopliteal artery deformation characteristics with stress and strain levels within the arterial tissue.

Comparison of in vitro human endothelial cell response to self-expanding stent deployment in a straight and curved peripheral artery simulator.

Haemodynamic forces have a synergistic effect on endothelial cell (EC) morphology, proliferation, differentiation and biochemical expression profiles. Alterations to haemodynamic force levels have been observed at curved regions and bifurcations of arteries but also around struts of stented arteries, and are also known to be associated with various vascular pathologies. Therefore, curvature in combination with stenting might create a pro-atherosclerotic environment compared with stenting in a straight vessel, but this has never been investigated. The goal of this study was to compare EC morphology, proliferation and differentiation within in vitro models of curved stented peripheral vessel models with those of straight and unstented vessels. These models were generated using both static conditions and also subjected to 24 h of stimulation in a peripheral artery bioreactor. Medical-grade silicone tubes were seeded with human umbilical vein endothelial cells to produce pseudovessels that were then stented and subjected to 24 h of physiological levels of pulsatile pressure, radial distention and shear stress. Changes in cell number, orientation and nitric oxide (NO) production were assessed in straight, curved, non-stented and stented pseudovessels. We report that curved pseudovessels lead to higher EC numbers with random orientation and lower NO production per cell compared with straight pseudovessels after 24 h of biomechanical stimulation. Both stented curved and stented straight pseudovessels had lower NO production per cell than corresponding unstented pseudovessels. However, in contrast to straight stented pseudovessels, curved stented pseudovessels had fewer viable cells. The results of this study show, for the first time, that the response of the vascular endothelium is dependent on both curvature and stenting combined, and highlight the necessity for future investigations of the effects of curvature in combination with stenting to fully understand effects on the endothelial layer.