The consequences of the mechanical environment of peripheral arteries for nitinol stenting

The use of stents in peripheral arteries has not been as successful as in coronary arteries, with high rates of restenosis and stent fracture common. Normal joint flexion induces a range of forces on the arteries, which has an unknown effect on the outcomes of stenting. The objective of this study is to determine how physiological levels of vessel bending and compression following stent implantation will influence the magnitude of stent stresses and hence the risks of fatigue fracture. A further objective is to compare how this mechanical environment will influence arterial stresses following implantation of either stainless steel or nitinol stents. To this end, models of both nitinol and stainless steel stents deployed in peripheral arteries were created, with appropriate loading conditions applied. At high levels of bending and compression, the strain amplitude threshold value for fatigue failure is exceeded for nitinol stents. Bending was predicted to induce high stresses in the artery following stenting, with higher arterial stresses predicted following implantation of a stainless steel stent compared to a nitinol stent. Both bending and compression may contribute to stent fracture by increasing the strain amplitude within the stent, with the dominant factor dependant on location within the arterial tree. For the specific stent types investigated in this study, the model predictions suggest that compression is the dominant mechanical factor in terms of stent fatigue in the femoral arteries, whereas bending is the most significant factor in the popliteal artery. To increase fatigue life and reduce arterial injury, location specific stent designs are required for peripheral arteries.     

Nitinol versus stainless steel stents: acute thrombogenicity study in an ex vivo porcine model

Acute and subacute stents thrombosis along with thrombus mediating neointimal proliferation within the stent struts remain major concerns in coronary stenting. Up to date, there is an obvious lack of data on the thrombogenicity of stent materials in physiological conditions. This study was performed to compare the relative thrombogenicity of nitinol versus stainless steel stents. Nitinol stents were laser cut to reproduce the exact geometry of the stainless steel Palmaz stents and tested in an ex vivo AV shunt porcine model under controlled conditions. Nitinol stents presented only small amounts of white and/or red thrombus principally located at the strut intersections while Palmaz stents clearly exhibited more thrombus. As a result, 125I-fibrin(ogen) adsorption and (111)I-platelets adhesion were significantly lower on nitinol than on stainless steel devices (36%, p = 0.03 for fibrin(ogen) and 63%, p = 0.01 for platelet). These results were confirmed by scanning electron observations showing different thrombus morphologies for nitinol and stainless steel. Along with the unique mechanical properties of nitinol, its promising haemocompatibility demonstrated in our study may promote their increasing use for both peripheral and coronary revascularization procedures.     

Fatigue and durability of Nitinol stents

Nitinol self-expanding stents are effective in treating peripheral artery disease, including the superficial femoral, carotid, and renal arteries. However, fracture occurrences of up to 50% have been reported in some stents after one year. These stent fractures are likely due to in vivo cyclic displacements. As such, the cyclic fatigue and durability properties of Nitinol-based endovascular stents are discussed in terms of an engineering-based experimental testing program. In this paper, the combined effects of cardiac pulsatile fatigue and stent-vessel oversizing are evaluated for application to both stents and stent subcomponents. In particular, displacement-controlled fatigue tests were performed on stent-like specimens processed from Nitinol microtubing. Fatigue data were collected with combinations of simulated oversizing conditions and pulsatile cycles that were identified by computer modeling of the stent that mimic in vivo deformation conditions. These data are analyzed with non-linear finite element computations and are illustrated with strain-life and strain-based constant-life diagrams. The utility of this approach is demonstrated in conjunction with 10 million cycle pulsatile fatigue tests of Cordis SMART Control^® Nitinol self-expanding stents to calculate fatigue safety factors and thereby predict in vivo fatigue resistance. These results demonstrate the non-linear constant fatigue-life response of Nitinol stents, whereby, contrary to conventional engineering materials, the fatigue life of Nitinol is observed to increase with increasing mean strain.     

不同连接筋结构的支架治疗椎动脉狭窄的力学分析

目的研究具有不同连接筋的支架对椎动脉狭窄的力学作用,以期为支架的设计以及介入治疗提供更加科学的指导。方法采用Pro/Engineer建立3种不同连接筋的支架模型(根据连接筋形状分别称为L-支架、V-支架和S-支架)和带有狭窄的椎动脉模型;使用ABAQUS有限元分析程序,对模型施加相同的边界条件,模拟3种支架在相同椎动脉模型中的展开过程。结果相比L-支架和V-支架,具有较好柔顺性的S-支架引起的血管应力较小,造成血管抻直的程度较弱;且S-支架上的应力和轴向短缩均较小,从而使得支架对血管造成的损伤较小。结论 3种支架中S-支架具有较好的治疗效果,可降低支架内再狭窄发生的可能性,且具有较好的临床应用前景。     

A link between stent radial forces and vascular wall remodeling: The discovery of an optimal stent radial force for minimal vessel restenosis

Coronary and peripheral artery disease (PAD) continue to be primary causes of morbidity and mortality in western nations; percutaneous transluminal angioplasty (PTA) with stenting has become a popular treatment. Unfortunately, restenosis is a significant problem following intravascular stent placement. This study considers the contribution of stent forces in vascular stenosis and remodeling to develop an equation for identifying the optimal stent force. z-Type stents of three radial forces [low (3.4 N), high (16.4 N), and ultrahigh (19.4 N)] were deployed into the iliac arteries of a juvenile porcine model. Vessel diameters were measured before, after deployment, and again at 30 days. At 30 days animals were killed and the vessels fixed in situ. After implantation, there was a significant increase in total thickness and neointimal hyperplasia with increasing stent force. The model for vessel radius and experimental data was in agreement. The model shows that maximum late‐term radius is achieved with a stent deployment stress of 480 kPa, which occurs at the end of the stress–strain curve nonlinear domain and beginning of the high-strain collagen domain. The results and calculations suggest that an optimal stent force exists that is subject to the geometry, structure, and mechanics of the target vessel. To achieve maximum late-term dilatation, stents should not produce stress in the vessel wall greater than the end of the transitional domain of the vessel's stress–strain curve. This finding is extremely important for vascular stent development and will be expanded to preliminary vessel wall injury and atherosclerotic models.     

Corrosion resistance of polyurethane-coated nitinol cardiovascular stents

Corrosion of metal stents implanted inside an artery can have two adverse effects: (1) tissue reaction and possible toxic effects from the metal ions leaching out of the stent, and (2) loss of mechanical strength of the stent caused by corrosion. The corrosion resistance of Nitinol (Nickel-Titanium) stents and its modulation with different film thickness of polymer coating was studied against an artificial physiological solution using a Potentiostat/Galvanostat and an electrochemical corrosion cell. The corrosion rate decreased rapidly from 275 microm/year for an uncoated surface down to less than 13 microm/year for a 30 microm thick polyurethane coating. Stainless steel (316L) and Nitinol both contain potentially toxic elements, and both are subject to stress corrosion. Minimization of corrosion can significantly reduce both tissue reaction and structural degradation.     

Assessment of tissue prolapse after balloon-expandable stenting: Influence of stent cell geometry

Restenosis is a re-narrowing or blockage of an artery at the same site where treatment, such as a balloon angioplasty or stent procedure, has already taken place. Several clinical trials have shown a significant reduction in the restenosis rates with endovascular stenting. The purpose of stenting is to maintain the arterial lumen open by a scaffolding action that provides radial support. However, stenting can cause a vascular injury during the deployment. Indeed, in-stent restenosis remains a major problem in percutaneous coronary intervention, requiring patients to undergo repeated procedures and surgery. The loading imposed by the deployment of the stent on the artery is involved in the restenosis process. Furthermore, it is well known that the stent design plays a role in the outcome of the stenting interventional procedure. This study compares the mechanical effects of the expansion of five different designs of balloon-expandable stents in a coronary artery by means of numerical models based on the finite element method. An index for the evaluation of the tissue prolapse based on the expanded configuration reached by the stent cells is proposed. The effects of the balloon inflation and deflation are included in the present study. Wall stresses and tissue prolapse of the vessel wall within the stent cells are evaluated and compared among the different stent designs. Results show that the printed area does not predict prolapse, and that the proposed index (PI) does correlate with tissue prolapse.     

Simulation and experimental observation of contact conditions between stents and artery models

Treatment of coronary artery stenosis with percutaneous coronary angioplasty and stenting is sometimes complicated by neointimal hyperplasia, possibly due to interaction of the stent with the arterial wall within a specific contact area. Therefore, we characterized the stress distribution at the contacts between the stent and the artery using mathematical and experimental modeling (an arterial cylinder model with a tube-like structure and an arterial stenosis model, consisting of a tube and plaque portion) and two kinds of link stents with different numbers of cells and links. First, the contact condition was investigated using a finite element method (FEM). Second, experimental visualization of the contact area between the stent and the artery models was performed. Comparison of the experimental results with the FEM analysis revealed that the contact area between the stent (with a high number of cells and links) and the artery model was distributed over the total surface of the stent. Further, values obtained from the experimental distribution and the calculated distribution were similar. These data indicate that experimental modeling and FEM analysis are useful methods for analyzing the relationship between stent structure and stent/wall stress distributions and may help guide the design of new stents.     

Corrosion resistance of polyurethane-coated Nitinol cardiovascular stents

Corrosion of metal stents implanted inside an artery can have two adverse effects: (1) tissue reaction and possible toxic effects from the metal ions leaching out of the stent, and (2) loss of mechanical strength of the stent caused by corrosion. The corrosion resistance of Nitinol (Nickel-Titanium) stents and its modulation with different film thickness of polymer coating was studied against an artificial physiological solution using a Potentiostat/Galvanostat and an electrochemical corrosion cell. The corrosion rate decreased rapidly from 275 μm/year for an uncoated surface down to less than 13 μm/year for a 30 μm thick polyurethane coating. Stainless steel (316L) and Nitinol both contain potentially toxic elements, and both are subject to stress corrosion. Minimization of corrosion can significantly reduce both tissue reaction and structural degradation.     

Comprehensive data visualization for high resolution endovascular carotid arterial wall imaging

Carotid angioplasty and stenting is a minimally invasive endovascular procedure that may benefit from in vivo high resolution imaging for monitoring the physical placement of the stent and potential complications. The purpose of this pilot study was to evaluate the ability of optical coherence tomography to construct high resolution 2D and 3D images of stenting in porcine carotid artery. Four Yorkshire pigs were anaesthetized and catheterized. A state-of-the-art optical coherence tomography (OCT) system and an automated injector were used to obtain both healthy and stented porcine carotid artery images. Data obtained were then processed for visualization. The state-of-the-art OCT system was able to capture high resolution images of both healthy and stented carotid arteries. High quality 3D images of healthy and stented carotid arteries were constructed, clearly depicting vessel wall morphological features, stent apposition and thrombus formation over the inserted stent. The results demonstrate that OCT can be used to generate high quality 3D images of carotid arterial stents for accurate diagnosis of stent apposition and complications under appropriate imaging conditions.     

A simplified in vivo approach for evaluating the bioabsorbable behavior of candidate stent materials

Metal stents are commonly used to revascularize occluded arteries. A bioabsorbable metal stent that harmlessly erodes away over time may minimize the normal chronic risks associated with permanent implants. However, there is no simple, low-cost method of introducing candidate materials into the arterial environment. Here, we developed a novel experimental model where a biomaterial wire is implanted into a rat artery lumen (simulating bioabsorbable stent blood contact) or artery wall (simulating bioabsorbable stent matrix contact). We use this model to clarify the corrosion mechanism of iron (≥99.5 wt %), which is a candidate bioabsorbable stent material due to its biocompatibility and mechanical strength. We found that iron wire encapsulation within the arterial wall extracellular matrix resulted in substantial biocorrosion by 22 days, with a voluminous corrosion product retained within the vessel wall at 9 months. In contrast, the blood-contacting luminal implant experienced minimal biocorrosion at 9 months. The importance of arterial blood versus arterial wall contact for regulating biocorrosion was confirmed with magnesium wires. We found that magnesium was highly corroded when placed in the arterial wall but was not corroded when exposed to blood in the arterial lumen for 3 weeks. The results demonstrate the capability of the vascular implantation model to conduct rapid in vivo assessments of vascular biomaterial corrosion behavior and to predict long-term biocorrosion behavior from material analyses. The results also highlight the critical role of the arterial environment (blood vs. matrix contact) in directing the corrosion behavior of biodegradable metals.     

An intriguing design concept to enhance the pulsatile fatigue life of self-expanding stents

Intravascular stenting has emerged as the primary treatment for vascular diseases and has received great attention from the medical community since its introduction two decades ago. The endovascular self-expanding stent is used to treat peripheral artery diseases; however, once implanted, these stents suffer from various cyclic motions caused by pulsatile blood pressure and daily activities. Due to this challenging environment, fatigue performance has become a critical issue for stent design. In this paper, a simple yet intriguing concept of stent design aimed at enhancing pulsatile fatigue life is investigated. The concept of this design is to shift the highly concentrated stresses/strains away from the crown and re-distribute them along the stress-free bar arm by tapering its strut width. Finite element models were developed to evaluate the mechanical integrity and pulsatile fatigue resistance of the stent to various loading conditions. Results show that the fatigue safety factor jumped to 2.5–3.0 times that of the standard stent with constant strut width. This is astonishing considering that the stent profile and scaffolding were not compromised. The findings of this paper provide an excellent approach to the optimization of future stent design to greatly improve stent fatigue performance.     

Fatigue behaviour of Nitinol peripheral stents: The role of plaque shape studied with computational structural analyses

Fatigue resistance of Nitinol stents implanted into femoro-popliteal arteries is a critical issue for the particular biomechanical environment of this district. Hip and knee joint movements due to the cyclic daily activity expose the superficial femoral artery (SFA), and therefore the implanted stents, to quite large and cyclic deformations influencing stent fatigue resistance. Objective of this work is to provide a tool based on finite element analysis able to evaluate the biomechanical effect of SFA on stent fatigue resistance. Computer simulations of the treatment of stenotic vessel by angioplasty and stenting and of the subsequent in vivo loading conditions (axial compression and bending) were carried out. Three different stenotic vessel models were defined, by keeping a constant stenosis rate and changing the plaque sharpness and number of stenoses. The fatigue behaviour was analysed comparing the amplitude and mean value distribution of the first principal strain in the whole stent for the different simulated conditions. Results showed that the maximum mean strain is similar in all the models, while the alternating strain is related to both plaque shape and loading conditions. In conclusion, this study confirms the requisite of replicating in vivo loading conditions. It also reveals the importance of taking into account the thickness variation of the vessel in the stenotic zone in the assessment of the stent fatigue resistance.     

Stent-induced coronary artery stenosis characterized by multimodal nonlinear optical microscopy

We demonstrate for the first time the applicability of multimodal nonlinear optical (NLO) microscopy to the interrogation of stented coronary arteries under different diet and stent deployment conditions. Bare metal stents and Taxus drug-eluting stents (DES) were placed in coronary arteries of Ossabaw pigs of control and atherogenic diet groups. Multimodal NLO imaging was performed to inspect changes in arterial structures and compositions after stenting. Sum frequency generation, one of the multimodalities, was used for the quantitative analysis of collagen content in the peristent and in-stent artery segments of both pig groups. Atherogenic diet increased lipid and collagen in peristent segments. In-stent segments showed decreased collagen expression in neointima compared to media. Deployment of DES in atheromatous arteries inhibited collagen expression in the arterial media.     

Model study of blood flow through a stent in the aorto-iliac bifurcation

Atherosclerotic ailments play a major role in industrial societies. Atherosclerotic disease causes stenotic narrowing of the arterial vessel system. These narrow passages can be widened with balloon angioplasty and stents are introduced to keep the passage open. In this study, stents designed for the aorto-iliac bifurcation are considered. Most of these stents used in peripheral arteries are self-expanding stents made from Nitinol, a thermo-reactive alloy. The insertion is done under radiographic control. However, the delicate metallic structure of the stent usually casts only a weak radiographic shadow and thus is difficult to detect. A stent with an innovative radio opaque tantalum marker (Luminexx, C.R. BARD--Angiomed, Karlsruhe), overcomes this problem. However, the markers extend into the blood flow and the question arises whether the markers may cause the generation of thrombi. In a model study in an enlarged model of the aorto-iliac bifurcation with an inserted stent the flow was visualized. The enlarged scale permits the observation and video recording of the flow in great detail. The Reynolds similarity is kept. A subsequent analysis of the flow in the vicinity of the markers shows a short residence time. These results indicate that the additional markers do not increase the risk of thrombus generation.     

Fluid and solid mechanical implications of vascular stenting

Vascular stents have emerged as an effective treatment for occlusive vascular disease. Despite their success and widespread use, outcomes for patients receiving stents are still hampered by thrombosis and restensosis. As arteries attempt to adapt to the mechanical changes created by stents, they may in fact create a new flow-limiting situation similar to that which they were intended to correct. In vitro fluid mechanics and solid mechanics studies of stented vessels have revealed important information about how stents alter the mechanical environment in the arteries into which they are placed. Adverse nonlaminar flow patterns have been demonstrated as well as remarkably high stress concentrations in the vessel wall. In vivo studies of stented vessels have also shown a strong relationship between stent design and their dynamic performance within arteries. Alterations in pressure and flow pulses distal to the stent have been observed, as well as regional changes in vascular compliance. Considering the influence of flow and stress on the vascular response and the suboptimal clinical outcomes associated with stenting, knowledge gained from stent/artery mechanics studies should play an increasingly important role in improving the long-term patency of these devices. © 2002 Biomedical Engineering Society. PAC2002: 8719Rr, 8780-y, 8719Uv     

Neutrophil-derived cathelicidin protects from neointimal hyperplasia

Percutaneous transluminal angioplasty with stent implantation is used to dilate arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release antiproliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may still lead to in-stent stenosis; they also show increased rates of late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery. Here, we examined the contribution of neutrophils and neutrophilic granule proteins to arterial healing after injury. We found that neutrophil-borne cathelicidin (mouse CRAMP, human LL-37) promoted reendothelization and thereby limited neointima formation after stent implantation. We then translated these findings to an animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coated with LL-37. This stent reduced in-stent stenosis in a mouse model of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy.     

Continuum damage model for bioresorbable magnesium alloy devices - Application to coronary stents

The main drawback of a conventional stenting procedure is the high risk of restenosis. The idea of a stent that "disappears" after having fulfilled its mission is very intriguing and fascinating, since it can be expected that the stent mass decreases in time to allow the gradual transmission of the mechanical load to the surrounding tissues owing to controlled dissolution by corrosion. Magnesium and its alloys are appealing materials for designing biodegradable stents. The objective of this work is to develop, in a finite element framework, a model of magnesium degradation that is able to predict the corrosion rate, thus providing a valuable tool for the design of bioresorbable stents. Continuum damage mechanics is suitable for modeling several damage mechanisms, including different types of corrosion. In this study, the damage is assumed to be the superposition of stress corrosion and uniform microgalvanic corrosion processes. The former describes the stress-mediated localization of the corrosion attack through a stress-dependent evolution law, while the latter affects the free surface of the material exposed to an aggressive environment. Comparisons with experimental tests show that the developed model can reproduce the behavior of different magnesium alloys subjected to static corrosion tests. The study shows that parameter identification for a correct calibration of the model response on the results of uniform and stress corrosion experimental tests is reachable. Moreover, three-dimensional stenting procedures accounting for interaction with the arterial vessel are simulated, and it is shown how the proposed modeling approach gives the possibility of accounting for the combined effects of an aggressive environment and mechanical loading.     

The influence of plaque composition on underlying arterial wall stress during stent expansion: The case for lesion-specific stents

Intracoronary stent implantation is a mechanical procedure, the success of which depends to a large degree on the mechanical properties of each vessel component involved and the pressure applied to the balloon. Little is known about the influence of plaque composition on arterial overstretching and the subsequent injury to the vessel wall following stenting. An idealised finite element model was developed to investigate the influence of both plaque types (hypercellular, hypocellular and calcified) and stent inflation pressures (9, 12 and 15 atm) on vessel and plaque stresses during the implantation of a balloon expandable coronary stent into an idealised stenosed artery. The plaque type was found to have a significant influence on the stresses induced within the artery during stenting. Higher stresses were predicted in the artery wall for cellular plaques, while the stiffer calcified plaque appeared to play a protective role by reducing the levels of stress within the arterial tissue for a given inflation pressure. Higher pressures can be applied to calcified plaques with a lower risk of arterial vascular injury which may reduce the stimulus for in-stent restenosis. Results also suggest that the risk of plaque rupture, and any subsequent thrombosis due to platelet deposition at the fissure, is greater for calcified plaques with low fracture stresses.