Assessment of structure integrity,corrosion behavior and microstructure change of AZ31B stent in porcine coronary arteries

Magnesium alloy coronary stent becomes a hot research topic due to its biodegradable character for avoiding late thrombosis and late restenosis. However, fracture of Mg alloy stent was a common issue after implantation. In this study, 18 drug-eluting biodegradable AZ31 B stents were implanted into porcine coronary arteries to assess its structural integrity, corrosion behavior and microstructure change in vivo.The coronary artery tissue responses to AZ31 B stent implantation were detected by quantitative coronary angiography and optical coherence tomography at the set time periods. In addition, further analyses were focused on the stent structure integrity, corrosion behaviors and the microstructure change of Mg alloy stents after implantation. A large number of fractures on stent struts were observed by high-resolution transmission X-ray tomography clearly. Moreover, degradation products, twins and grain refinement that appeared in Mg alloy stent matrix after implantation were also observed during the study. Inferred from this study, it is shown that the loss of AZ31 B stent structural integrity may be the result of stress concentration, degradation and microstructure change.     

Finite element analyses for design evaluation of biodegradable magnesium alloy stents in arterial vessels

Biodegradable magnesium alloy stents (MAS) can provide a great benefit for diseased vessels and avoid the long-term incompatible interactions between vessels and permanent stent platforms. However, the existing MAS showed insufficient scaffolding to the target vessels due to short degradation time. In this study, a three dimensional finite element model combined with a degradable material model of AZ31 (Al 0.03, Zn 0.01, Mn 0.002 and Mg balance, mass percentage) was applied to three different MAS designs including an already implanted stent (Stent A), an optimized design (Stent B) and a patented stent design (Stent C). One ring of each design was implanted through a simulation in a vessel model then degraded with the changing interaction between outer stent surface and the vessel. Results showed that a proper stent design (Stent B) can lead to an increase of nearly 120% in half normalized recoil time of the vessel compared to the Stent A; moreover, the expectation that the MAS design, with more mass and optimized mechanical properties, can increase scaffolding time was verified numerically. The Stent C has more materials than Stent B; however, it only increased the half normalized recoil time of the vessel by nearly 50% compared to the Stent A because of much higher stress concentration than that of Stent B. The 3D model can provide a convenient design and testing tool for novel magnesium alloy stents.     

Characterization and in vivo evaluation of a bio-corrodible nitrided iron stent

A bio-corrodible nitrided iron stent was developed using a vacuum plasma nitriding technique. In the nitrided iron stents, the tensile strength, radial strength, stiffness and in vitro electrochemical corrosion rate were significantly increased compared with those of the control pure iron stent. To evaluate its performance in vivo, the deployment of the nitrided iron stents in juvenile pig iliac arteries was performed. At 3 or 6 months postoperatively, the stented vessels remained patent well; however, slight luminal loss resulting from intimal hyperplasia and relative stenosis of the stented vessel segment with piglets growth were observed by 12 months; no thrombosis or local tissue necrosis was found. At 1 month postoperatively, a nearly intact layer of endothelial cells formed on the stented vessel wall. Additionally, a decreased inflammation scoring, considerably corroded struts and corrosion products accumulation were seen. These findings indicate the potential of this nitrided iron stent as an attractive biodegradable stent.     

可降解血管支架材料降解行为研究进展

目前可降解血管支架材料包括聚合物、镁合金、铁合金及锌合金,它们的降解特性直接影响其作为血管支架植入后的支撑能力、局部反应和血管修复的预后。聚合物降解时间较易调整、生物相容性较好,但力学性能不足;镁合金的降解存在降解速率快、释氢反应和微环境pH值变化较大的问题;铁合金降解速率太慢;锌合金的降解速率适中,是近年可降解血管内植入材料研究热点。除了材料自身的特性,可降解材料的血管内降解行为还受到环境的离子浓度、酶、pH值和温度等多种因素的影响。综述了目前不同血管内可降解支架材料在模拟体液及动物体内生物降解行为的研究结果,以期为血管内可降解材料研究和产品开发提供参考。     

管腔内支架用金属材料的生物相容性及其表面改性

管腔内金属支架是用于植入人体各管道狭窄处起支撑作用的医疗器械,因其与人体组织直接接触,故对支架的生物相容性的研究十分重要。本文对用于管腔内支架的３１６Ｌ不锈钢和ＮｉＴｉ合金的耐腐蚀性和生物相容性进行了综合评述;并以冠状动脉支架为应用背景,着重分析了影响血管内支架血液相容性的因素,提出了对支架进行表面改性处理以提高其血液相容性的技术路线。     

Mechanical behavior of peripheral stents and stent-vessel interaction: A computational study

In this paper stents employed to treat peripheral artery disease are analyzed through a three-dimensional finite-element approach, based on a large-strain and large-displacement formulation. Aiming to evaluate the influence of some stent design parameters on stent mechanics and on the biomechanical interaction between stent and arterial wall, quasi-static and dynamic numerical analyses are carried out by referring to computational models of commercially and noncommercially available versions of both braided self-expandable stents and balloon-expandable stents. Addressing isolated device models, opening mechanisms and flexibility of both opened and closed stent configurations are numerically experienced. Moreover, stent deployment into a stenotic peripheral artery and possible postdilatation angioplasty (the latter for the self-expandable device only) are simulated by considering different idealized vessel geometries and accounting for the presence of a stenotic plaque. Proposed results highlight important differences in the mechanical response of the two types of stents, as well as a significant influence of the vessel shape on the stress distributions arising upon the artery-plaque system. Finally, computational results are used to assess both the stent mechanical performance and the effectiveness of the stenting treatment, allowing also to identify possible critical conditions affecting the risk of stent fracture, tissue damage, and/or pathological tissue response.     

Biocompatibility of Coronary Stent Materials: Effect of Electrochemical Polishing

Percutaneous Transluminal Coronary Revascularization (PTCR) is now a widely accepted treatment modality for atherosclerotic coronary artery disease. Current multicenter randomized trials comparing PTCR with the more invasive Coronary Artery Bypass Grafting could not show long‐term significant survival differences. During the last two decades progress has been made to further optimize PTCR. The most logic approach to treat atherosclerotic coronary narrowings is to remove the atherosclerotic material using especially developed devices. Several trials, however, could not show a significant beneficial outcome after use of these devices compared to plain old balloon angioplasty. Another approach was to implant a coronary prothesis (stent), scaffolding the diseased coronary artery after PTCA. This approach resulted in a decreased restenosis rate at follow‐up. The beneficial effects of stenting, however, was not found to be related to the inhibition of the neointimal cellular proliferation after vascular injury, but simply to be the mechanical result of overstretching of the treated vessel segment. The most important remaining clinical problem after stenting remains the neointimal hyperplasia within the stent, resulting in a significant stent narrowing in 13 to 30 % of patients. Further efforts to improve the clinical results of coronary stenting should focus on the reduction of this neointimal hyperplasia. Neointimal hyperplasia after stent implantation results from (1) a healing response to the injury caused by the stent implantation and (2) a foreign body response to the stent itself. Factors that seem to influence the neointimal hyperplastic response are genetic, local disease related, stent delivery related and stent related factors. Biocompatibilisation of coronary stents by looking for more biocompatible metal alloys, optimized surface characteristics and optimized stent designs should result in a better late patency. Furthermore drug eluting and radioactive stents are under development in order to decrease the neointimal hyperplastic response.     

不同材料冠状动脉支架膨胀行为分析

冠状动脉支架作为经皮穿刺冠状动脉成形术中保持病变血管畅通的核心器件,其在手术过程中受球囊作用的扩张特性以及球囊撤出后的反弹行为对支架植入术的成功有着重要的影响.利用有限元的方法系统,建立专有支架单独膨胀和血管支架膨胀模型,分析了316L不锈钢和L605钴铬合金两种材料支架筋尺寸和支架扩张尺度的变化及血管对其膨胀行为的影响.结果显示,支架所选材料是决定支架膨胀行为的主要因素,L605材料支架所需的临界内压力及反弹行为明显大于316L不锈钢支架;材料一定时,增加支架筋的宽度或厚度提高支架迅速扩张临界内压力;支架轴向长度的变化只与结构和最终膨胀状态相关.有限元模拟对支架性能的评价和设计有一定指导意义.     

Fabrication of Mg alloy tubes for biodegradable stent application

Though Mg alloys are promising candidates for biodegradable stents, it is very difficult to fabricate stent tubes with high dimensional accuracy using Mg alloys because of their low deformability. This study aimed to develop thin-walled, high-quality Mg alloy tubes with good performance in stent applications. Cold drawing with a fixed mandrel was carried out for extruded Mg-0.8%Ca and AZ61 alloy tubes using optimized drawing parameters and lubrication, and stent tubes with 1.5–1.8 mm outer diameter and 150 μm thickness were fabricated. A dimensional evaluation showed that the tube dimensional errors were within 0.02–2.5%. Also, an immersion test of pure Mg with different crystal orientations showed that the crystal orientation affected the corrosion properties, results that are the same with other Mg alloys. The crystal orientation of the stent tube could be controlled by changing the deformation amount and direction in the drawing, showing that it is possible to further improve the biodegradability of stents by approaching their fabrication from a processing aspect.     

Analysis of the whole implementation process and optimization of a Nitinol superelastic stent

Nitinol superelastic stents have been widely used to treat the vascular stenosis due to its excellent mechanical behavior and biocompatibility. However, there exist conflicts between the functional properties and mechanical properties of the stent. An optimization method has been employed to deal with the conflictions with the consideration of the whole implementation process of the stent in this paper. A straight vascular with tumor inside is considered. A commonly used NiTinol superleastic stent with diamond shape strut is employed. The vascular wall tissue and stenotic plaque are also treated as hyperelastic materials. Softwares Isight, ABAQUS and Solidworks are utilized to perform the optimization job. It can be seen that the stresses are high at the areas around the fillets of the stent due to the stress concentration from a primary analysis. Therefore, the two fillets radius, thickness and radius of the stent are chosen as four optimization variables. The optimization object is to decrease the maximum stress of stent and increase the displacement of the plaque. After the optimization, the maximum stress can be decreased by 8.2 %, which implies that the stent's work life can be increased. The stenosis of the blood vessel can be decreased from 56 % to 40.0 %.     

Practicability and Limitations of Finite Element Simulation of the Dilation Behaviour of Coronary Stents

After first implantation of a metallic stent into cardiac vessels in 1986 stent implantation has become a standard technique for treatment of coronary heart disease. During implantation of balloon‐expandable stents, the structure of the stent undergoes high plastic deformation. Despite the fact, that stents are used for more than 15 years nearly no information about the mechanical and micro structural process during dilation are known. The present paper presents a detailed study and comparison of the experimental and the simulated expansion behaviour of metallic stents. Used material models are discussed and crystallographic details are presented. Dilation curves describe the behaviour of balloon‐expandable coronary stents. The dilation behaviour depends on both the materials properties and the design of the stent. A numerical simulation of the dilation process by means of FE is suitable. A comparison of the experimental measurement and the numerical simulation demonstrates, that a Cauchy stress‐strain material model should be used for numerical simulations. A local failure criterion is introduced, which considers void initiation as a criterion for mechanical failure.     

Surface Modification on Biodegradable Magnesium Alloys as Orthopedic Implant Materials to Improve the Bio-adaptability:A Review

Magnesium(Mg) and its alloys as a novel kind of biodegradable material have attracted much fundamental research and valuable exploration to develop its clinical application. Mg alloys degrade too fast at the early stage after implantation, thus commonly leading to some problems such as osteolysis, early fast mechanical loss, hydric bubble aggregation, gap formation between the implants and the tissue. Surface modification is one of the effective methods to control the degradation property of Mg alloys to adapt to the need of organism. Some coatings with bioactive elements have been developed, especially for the micro-arc oxidation coating, which has high adhesion strength and can be added with Ca, P, and Sr elements. Chemical deposition coating including bio-mimetic deposition coating, electro-deposition coating and chemical conversion coating can provide good anticorrosion property as well as better bioactivity with higher Ca and P content in the coating. From the biodegradation study, it can be seen that surface coating protected the Mg alloys at the early stage providing the Mg alloy substrate with lower degradation rate. The biocompatibility study showed that the surface modification could provide the cell and tissue stable and weak alkaline surface micro-environment adapting to the cell adhesion and tissue growth.The surface modification also decreased the mechanical loss at the early stage adapting to the loadbearing requirement at this stage. From the interface strength between Mg alloys implants and the surrounding tissue study, it can be seen that the surface modification improved the bio-adhesion of Mg alloys with the surrounding tissue, which is believed to be contributed to the tissue adaptability of the surface modification. Therefore, the surface modification adapts the biodegradable magnesium alloys to the need of biodegradation, biocompatibility and mechanical loss property. For the different clinical application, different surface modification methods can be provided to adapt to the clinical requirements for the Mg alloy implants.     

Bone-like matrix formation on magnesium and magnesium alloys

Mg metal and its alloys have promise as a biocompatible, degradable biomaterials. This work evaluates the potential of in vitro cell culture work with osteoblast-like cells on Mg based materials, and investigates cell differentiation and growth on Mg alloyed with various non-toxic or low-toxicity elements. Mg based substrates support the adhesion, differentiation and growth of stromal cells towards an osteoblast-like phenotype with the subsequent production of a bone like matrix under in vitro conditions. No significant difference in the final tissue layer is observed on pure Mg, an AZ21 alloy or a 0.5 wt% Ca alloy. Only a 0.8 wt% Ca alloy which shows complete structural disintegration shows minimal cell growth. Due to association of non-soluble degradation products formed when Mg is incubated in physiological-like fluid, mass changes typically used to report Mg degradation are not viable estimates of degradation. Methods quantifying the time dependent change in the mechanical integrity of samples as a function of incubation time are required for a proper assessment of Mg degradation. We conclude that in vitro cell culture of bone cells on Mg substrates is expected to be a viable screening technique to assess the relative biological activity of Mg-based materials.     

Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow?

Intimal hyperplasia (IH) is a leading cause of obstruction of vascular interventions, including arterial stents, bypass grafts and arteriovenous grafts and fistulae. Proposals to account for arterial stent-associated IH include wall damage, low wall shear stress (WSS), disturbed flow and, although not widely recognized, wall hypoxia. The common non-planarity of arterial geometry and flow, led us to develop a bare-metal, nitinol, self-expanding stent with three-dimensional helical-centreline geometry. This was deployed in one common carotid artery of healthy pigs, with a straight-centreline, but otherwise identical (conventional) stent deployed contralaterally. Both stent types deformed the arteries, but the helical-centreline device additionally deformed them helically and caused swirling of intraluminal flow. At sacrifice, one month post stent deployment, histology revealed significantly less IH in the helical-centreline than straight-centreline stented vessels. Medial cross-sectional area was not significantly different in helical-centreline than straight-centreline stented vessels. By contrast, luminal cross-sectional area was significantly larger in helical-centreline than straight-centreline stented vessels. Mechanisms considered to account for those results include enhanced intraluminal WSS and enhanced intraluminal blood–vessel wall mass transport, including of oxygen, in the helical-centreline stented vessels. Consistent with the latter proposal, adventitial microvessel density was lower in the helical-centreline stented than straight-centreline stented vessels.     

Dynamic behaviors of a Ca-P coated AZ31B magnesium alloy during in vitro and in vivo degradations

Surface modification can be an effective way to control the biodegradation behavior of magnesium alloys and even improve their biological properties. Much attention has been paid to the initial protection ability and biological properties of magnesium alloys coating. In this work, the dynamic behaviors of a Ca-P coated AZ31B magnesium alloy during the degradations in vitro and in vivo, including hemolysis, mechanical loading capability and implantation in animals, were investigated. The hemolytic rates of the alloy with and without coating were all declined to be lower than 5% after more than 20 days immersion in PBS, though an increase happened to the alloy at the early immersion of 3-7 days. Reduction of the mechanical loading capacity was gradually evolved for the coated alloy and the peak load retention of 85% was still maintained after 120 days degradation. The in vivo implantation indicated that the Ca-P coated AZ31B alloy showed a more suitable time dependent degradation behavior which was favorable for growth of the new tissue and the healing dynamics of bones, making it a promising choice for medical application.     

Comparison of modified injection molding and conventional machining in biodegradable behavior of perforated cannulated magnesium hip stents

In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate injection of biomaterials.The microstructure,mechanical performance,corrosion behavior,and biocompatibility were comparably studied.Scanning electron microscopy(SEM)and energy dispersive spectroscopy(EDS)showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process.After immersion in SBF,machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents.Corrosion resistance was improved via paraffin-filling.Consistently,the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones,which was improved by paraffin-filling treatment as well.These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required,which could be enhanced by designing canal-filling injection of biomaterials as well.     

Analysis of the compression process and dimensional optimization of self‐expanding stent of a nickel titanium alloy

The vascular stents are important devices introduced into the vessel to protect the lumen from unfriendly stenosis so that the blood can flow naturally. During its implantation to the vessel, the stent should be compressed to a delivery system with very small dimension to accomplish the minimal invasive operation. At this stage, the stent will withstand very large stresses which will cause large damages in the structure. In this paper, the compression process of the stent was analyzed by finite element analysis method with software ABAQUS. The stress, strain and martensite volume fraction distributions were investigated at the end compression. Results show that the stent fillets are the dangerous areas for the potential failure. Subsequently, the dimensional optimization was performed to decrease the maximum concentration stress. After the optimization, the maximum stress can be decreased by 14.2%, which means the stent's work life can be increased.     

Long-term biodegradation and associated hydrogen evolution of duplex-structured Mg-Li-Al-(RE) alloys and their mechanical properties

Preliminary in vivo tests of two magnesium alloys, i.e. AE21 and WE43, as biodegradable vascular stent materials, have yielded encouraging results. However, their degradation is desired to be prolonged, mechanical stability over a defined time improved and ductility needed for stent expansion enhanced. A search for alternative magnesium alloys that can better meet these clinical requirements is needed. The present research aimed to evaluate the long-term degradation behavior, hydrogen evolution rates and mechanical properties of three lithium-containing magnesium alloys, namely LA92, LAE912 and LAE922 with a duplex crystal structure, in comparison with those of a WE-type alloy. Immersion tests in Hank's balanced salt solution for 600 days showed that the LA92 alloy degraded much less than the LAE912 and the LAE922 alloys. It even outperformed the WE-type alloy after immersion for 94 days. Moreover, unlike the other three alloys investigated, the LA92 alloy displayed a steady hydrogen evolution rate over the whole period of immersion tests. In addition, it possessed an elongation value of 33%, being much higher than the WE-type alloy. Thus, this alloy has a greater potential of meeting the requirements of radially expandable stents in mechanical properties and degradation performance.     

Beitrag zur Untersuchung des Ermüdungsverhaltens von Koronarstents

Comments to the Investigation of Fatigue Properties of Coronary Stents Since 1986 PTCA with implantation of a stent became a more and more important invasive method of treatment for coronary heart disease. The stent implanted during PTCA has to sustain a combined load of mechanical and chemical load. The pulsating artery leads to an expansion and cyclic mechanical load on the implanted stent. To eliminate the possibility of fail in vivo stents have to be tested regarding fatigue behaviour. As result of the complex geometry and the up to now not well investigated qualities of oligocrystalline structures [1], so far fatigue properties of stents can only be carried out on the implants themselves. Additionally stent design plays a decisive role in terms of mechanical factors.     

A review on biodegradable materials for cardiovascular stent application

A stent is a medical device designed to serve as a temporary or permanent internal scaffold to maintain or increase the lumen of a body conduit. The researchers and engineers diverted to investigate biodegradable materials due to the limitation of metallic materials in stent application such as stent restenosis which requires prolonged anti platelet therapy, often result in smaller lumen after implantation and obstruct re-stenting treatments. Biomedical implants with temporary function for the vascular intervention are extensively studied in recent years. The rationale for biodegradable stent is to provide the support for the vessel in predicted period of time and then degrading into biocompatible constituent. The degradation of stent makes the re-stenting possible after several months and also ameliorates the vessel wall quality. The present article focuses on the biodegradable materials for the cardiovascular stent. The objective of this review is to describe the possible biodegradable materials for stent and their properties such as design criteria, degradation behavior, drawbacks and advantages with their recent clinical and preclinical trials.