Shape-Setting of Self-Expanding Nickel-Titanium Laser-Cut and Wire-Braided Stents to Introduce a Helical Ridge.

PURPOSE: Altered hemodynamics caused by the presence of an endovascular device may undermine the success of peripheral stenting procedures. Flow-enhanced stent designs are under investigation to recover physiological blood flow patterns in the treated artery and reduce long-term complications. However, flow-enhanced designs require the development of customised manufacturing processes that consider the complex behaviour of Nickel-Titanium (Ni-Ti). While the manufacturing routes of traditional self-expanding Ni-Ti stents are well-established, the process to introduce alternative stent designs is rarely reported in the literature, with much of this information (especially related to shape-setting step) being commercially sensitive and not reaching the public domain, as yet. METHODS: A reliable manufacturing method was developed and improved to induce a helical ridge onto laser-cut and wire-braided Nickel-Titanium self-expanding stents. The process consisted of fastening the stent into a custom-built fixture that provided the helical shape, which was followed by a shape-setting in air furnace and rapid quenching in cold water. The parameters employed for the shape-setting in air furnace were thoroughly explored, and their effects assessed in terms of the mechanical performance of the device, material transformation temperatures and surface finishing. RESULTS: Both stents were successfully imparted with a helical ridge and the optimal heat treatment parameters combination was found. The settings of 500 °C/30 min provided mechanical properties comparable with the original design, and transformation temperatures suitable for stenting applications (Af = 23.5 °C). Microscopy analysis confirmed that the manufacturing process did not alter the surface finishing. Deliverability testing showed the helical device could be loaded onto a catheter delivery system and deployed with full recovery of the expanded helical configuration. CONCLUSION: This demonstrates the feasibility of an additional heat treatment regime to allow for helical shape-setting of laser-cut and wire-braided devices that may be applied to further designs.

Recommendations for finite element modelling of nickel-titanium stents-Verification and validation activities.

The objective of this study is to present a credibility assessment of finite element modelling of self-expanding nickel-titanium (Ni-Ti) stents through verification and validation (VV) activities, as set out in the ASME VV-40 standard. As part of the study, the role of calculation verification, model input sensitivity, and model validation is examined across three different application contexts (radial compression, stent deployment in a vessel, fatigue estimation). A commercially available self-expanding Ni-Ti stent was modelled, and calculation verification activities addressed the effects of mesh density, element integration and stable time increment on different quantities of interests, for each context of use considered. Sensitivity analysis of the geometrical and material input parameters and validation of deployment configuration with in vitro comparators were investigated. Results showed similar trends for global and local outputs across the contexts of use in response to the selection of discretization parameters, although with varying sensitivities. Mesh discretisation showed substantial variability for less than 4 × 4 element density across the strut cross-section in radial compression and deployment cases, while a finer grid was deemed necessary in fatigue estimation for reliable predictions of strain/stress. Element formulation also led to substantial variation depending on the chosen integration options. Furthermore, for explicit analyses, model results were highly sensitive to the chosen target time increment (e.g., mass scaling parameters), irrespective of whether quasistatic conditions were ensured (ratios of kinetic and internal energies below 5%). The higher variability was found for fatigue life simulation, with the estimation of fatigue safety factor varying up to an order of magnitude depending on the selection of discretization parameters. Model input sensitivity analysis highlighted that the predictions of outputs such as radial force and stresses showed relatively low sensitivity to Ni-Ti material parameters, which suggests that the calibration approaches used in the literature to date appear reasonable, but a higher sensitivity to stent geometry, namely strut thickness and width, was found. In contrast, the prediction of vessel diameter following deployment was least sensitive to numerical parameters, and its validation with in vitro comparators offered a simple and accurate (error ~ 1-2%) method when predicting diameter gain, and lumen area, provided that the material of the vessel is appropriately characterized and modelled.

Design and Verification of a Novel Perfusion Bioreactor to Evaluate the Performance of a Self-Expanding Stent for Peripheral Artery Applications.

Endovascular stenting presents a promising approach to treat peripheral artery stenosis. However, a significant proportion of patients require secondary interventions due to complications such as in-stent restenosis and late stent thrombosis. Clinical failure of stents is not only attributed to patient factors but also on endothelial cell (EC) injury response, stent deployment techniques, and stent design. Three-dimensional in vitro bioreactor systems provide a valuable testbed for endovascular device assessment in a controlled environment replicating hemodynamic flow conditions found in vivo. To date, very few studies have verified the design of bioreactors based on applied flow conditions and their impact on wall shear stress, which plays a key role in the development of vascular pathologies. In this study, we develop a computationally informed bioreactor capable of capturing responses of human umbilical vein endothelial cells seeded on silicone tubes subjected to hemodynamic flow conditions and deployment of a self-expanding nitinol stents. Verification of bioreactor design through computational fluid dynamics analysis confirmed the application of pulsatile flow with minimum oscillations. EC responses based on morphology, nitric oxide (NO) release, metabolic activity, and cell count on day 1 and day 4 verified the presence of hemodynamic flow conditions. For the first time, it is also demonstrated that the designed bioreactor is capable of capturing EC responses to stent deployment beyond a 24-hour period with this testbed. A temporal investigation of EC responses to stent implantation from day 1 to day 4 showed significantly lower metabolic activity, EC proliferation, no significant changes to NO levels and EC's aligning locally to edges of stent struts, and random orientation in between the struts. These EC responses were indicative of stent-induced disturbances to local hemodynamics and sustained EC injury response contributing to neointimal growth and development of in-stent restenosis. This study presents a novel computationally informed 3D in vitro testbed to evaluate stent performance in presence of hemodynamic flow conditions found in native peripheral arteries and could help to bridge the gap between the current capabilities of 2D in vitro cell culture models and expensive pre-clinical in vivo models.

Oversizing of self-expanding Nitinol vascular stents - A biomechanical investigation in the superficial femoral artery.

Despite being commonly employed to treat peripheral artery disease, self-expanding Nitinol stents are still associated with relatively high incidence of failure in the mid- and long-term due to in-stent restenosis or fatigue fracture. The practice of stent oversizing is necessary to obtain suitable lumen gain and apposition to the vessel wall, though it is regarded as a potential cause of negative clinical outcomes when mis-sizing occurs. The objective of this study was to develop a computational model to provide a better understanding of the structural effects of stent sizing in a patient-specific scenario, considering oversizing ratio OS, defined as the stent nominal diameter to the average vessel diameter, between 1.0 and 1.8. It was found that OS < 1.2 resulted in problematic short-term outcomes, with poor lumen gain and significant strut malapposition. Oversizing ratios that were in the range 1.2 ≤ OS ≤ 1.4 provided the optimum biomechanical performance following implantation, with improved lumen gain, reduced incomplete stent apposition and favourable predicted long-term fatigue performance. Excessive oversizing, OS > 1.4, did not provide any further benefit in outcomes, showing limited increases in lumen gain and unfavourable long-term performance, with higher mean strain values predicted from the fatigue analysis. Therefore, our findings predict that the optimal oversizing ratio for self-expanding Nitinol stents is in the range of 1.2 ≤ OS ≤ 1.4, which is similar to clinical observations, with this study providing detailed insight into the biomechanical basis for this.

Formation of Vortices in Idealised Branching Vessels: A CFD Benchmark Study.

PURPOSE: Atherosclerosis preferentially occurs near the junction of branching vessels, where blood recirculation tends to occur (Malek et al. in J Am Med Assoc 282(21):2035-2042, 1999, https://doi.org/10.1001/jama.282.21.2035 ). For decades, CFD has been used to predict flow patterns such as separation and recirculation zones in hemodynamic models, but those predictions have rarely been validated with experimental data. In the context of verification and validation (V&V), we first conduct a CFD benchmark calculation that reproduces the vortex detection experiments of Karino and Goldsmith (1980) with idealised branching blood vessels (Karino and Goldsmith in Trans. Am. Soc. Artif. Internal Organs 26:500-506, 1980). The critical conditions for the formation of recirculation vortices, the so-called critical Reynolds numbers, are the main parameters for comparison with the experimental data to demonstrate the credibility of the CFD workflow. We then characterise the wall shear stresses and develop a surrogate model for the size of formed vortices. METHODS: An automated parametric study generating more than 12,000 CFD simulations was performed, sweeping the geometries and flow conditions found in the experiments by Karino and Goldsmith. The flow conditions were restricted to steady-state laminar flow, with a range of inflow Reynolds numbers up to 350, with various flow ratios between the main branch outlet and side branch outlet. The side branch diameter was scaled relative to the main branch diameter, ranging from 1.05/3 to 3/3; and the branching angles ranged in size from [Formula: see text] to [Formula: see text]. Recirculation vortices were detected by the inversion of the velocity vector at certain locations, as well as by the inversion of the wall shear stress (WSS) vector. RESULTS: The CFD simulations demonstrated good agreement with the experimental data on the critical Reynolds numbers. The spatial distributions of WSS on each branch were analysed to identify potential regions of disease. Once a vortex is formed, the size of the vortex increases by the square root of the Reynolds number. The CFD data was fitted to a surrogate model that accurately predicts the vortex size without the need to run computationally more expensive CFD simulations. CONCLUSIONS: This benchmark study validates the CFD simulation of vortex detection in idealised branching vessels under comprehensive flow conditions. This work also proposes a surrogate model for the size of the vortex, which could reduce the computational requirements in the studies related to branching vessels and complex vascular systems.

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.