Magnesium Stents Research Articles

Plasma electrolytic oxidation of AZ31 magnesium stents for degradation rate control

Cardiovascular disease caused by the accumulation of atheroma plaques in the coronary arteries and the subsequent decrease in the blood flow through the affected vessel, known as atherosclerosis, is responsible for a high percentage of deaths worldwide. Angioplasty is practiced to treat atherosclerosis which involves inserting a stent inside the occluded vessel to expand it and restore normal blood flow. In this work, temporary biodegradable stents made of AZ31 magnesium alloy have been fabricated using photo-chemical etching. The stents were coated via plasma electrolytic oxidation (PEO) technique. The radial strength of the stents was evaluated by cyclic compression, and the corrosion protection provided by the PEO coatings was studied by electrochemical and in vitro corrosion tests respectively. The stents showed an optimal maximum radial force of 0.147 N/mm and revealed elastic recuperation lower than 7 % of the total deformation after expansion. The applied PEO coating helped to control the corrosion of the magnesium alloy, delaying its initiation and, once it has started, decreased the degradation rate compared with the bare AZ31 samples. Thus, the stents treated with the PEO coatings developed in this research present promising results for their use as temporary medical devices used in angioplasty.

Aneurysm healing following treatment with biodegradable embolization materials: assessment in a rat sidewall aneurysm model

BackgroundBiodegradable materials that dissolve after aneurysm healing are promising techniques in the field of neurointerventional surgery. We investigated the effects of various bioabsorable materials in combination with degradable magnesium alloy...

Preliminary results of absorbable magnesium stent for treating eustachian tube dysfunction in a porcine model.

Absorbable magnesium (Mg) stents have an attractive biocompatibility and rapid degradation rate, but their degradable behavior and efficacy in the Eustachian tube (ET) have not yet been investigated. In this study, the degradable behavior of the Mg stent in artificial nasal mucus was evaluated. The Mg stents in the porcine ET model were also investigated to evaluate their safety and efficacy. Four Mg stents were placed into the four ETs of two pigs. The mass loss rate of the Mg stents gradually decreased over time. The decrease rates were 30.96% at one week, 49.00% at two weeks, and 71.80% at four weeks. On the basis of histological findings, the thickness of submucosal tissue hyperplasia and the degree of inflammatory cell infiltration significantly decreased at four weeks compared with two weeks. Biodegradation of the Mg stent occurred before tissue proliferative reactions, and the ET patency was successfully maintained without stent-induced tissue hyperplasia at four weeks. The Mg stent that biodegrades rapidly seems to be effective and safe in porcine ET. Further investigation is required to verify the optimal stent shape and indwell period in the ET.

Electrochemical Impedance Spectroscopy (EIS) of parylene coated magnesium stents in organic solvent to study early corrosion control

Layers on stents of Mg-Nd-Zn-Zr alloy, after different treatments were studied by electrochemical techniques in an organic electrolyte. Electrochemical impedance results show a constant-phase-element (CPE) behavior, which was attributed to the layers on stent surface, as well as diffusion impedance associated with Mg2+ ions diffusion. Power law model was suggested to characterize electrical properties of the layers. Additionally, samples with oxide layers presented a high-frequency distribution which was well described by complex ohmic impedance. Compared with bare and plasma pre-treated stents, the parylene coatings showed lower capacitances values, associated with a thicker layer which is maintained after crimping and expansion.

Biohybrid elastin-like venous valve with potential for in situ tissue engineering.

Chronic venous insufficiency (CVI) is a leading vascular disease whose clinical manifestations include varicose veins, edemas, venous ulcers, and venous hypertension, among others. Therapies targeting this medical issue are scarce, and so far, no single venous valve prosthesis is clinically available. Herein, we have designed a bi-leaflet transcatheter venous valve that consists of (i) elastin-like recombinamers, (ii) a textile mesh reinforcement, and (iii) a bioabsorbable magnesium stent structure. Mechanical characterization of the resulting biohybrid elastin-like venous valves (EVV) showed an anisotropic behavior equivalent to the native bovine saphenous vein valves and mechanical strength suitable for vascular implantation. The EVV also featured minimal hemolysis and platelet adhesion, besides actively supporting endothelialization in vitro, thus setting the basis for its application as an in situ tissue engineering implant. In addition, the hydrodynamic testing in a pulsatile bioreactor demonstrated excellent hemodynamic valve performance, with minimal regurgitation (<10%) and pressure drop (<5 mmHg). No stagnation points were detected and an in vitro simulated transcatheter delivery showed the ability of the venous valve to withstand the implantation procedure. These results present a promising concept of a biohybrid transcatheter venous valve as an off-the-shelf implant, with great potential to provide clinical solutions for CVI treatment.

Biodegradable PTX-PLGA-coated magnesium stent for benign esophageal stricture: An experimental study

Biodegradable stents can degrade step by step and thereby avoid secondary removal by endoscopic procedures in contrast to metal stents. Herein, a biodegradable composite stent, a magnesium (Mg)-based braided stent with a surface coating of poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX), was designed and tested. By adding this drug-loaded polymer coating, the radial force of the stent increased from 33 Newton (N) to 83 N. PTX was continuously released as the stent degraded, and the in vitro cumulative drug release in phosphate-buffered saline for 28 days was 115 ± 13.5 μg/mL at pH = 7.4 and 176 ± 12 μg/mL at pH = 4.0. There was no statistically significant difference in the viability of fibroblasts of stent extracts with different concentration gradients (P > 0.05), while the PTX-loaded stents effectively promoted fibroblast apoptosis. In the animal experiment, the stents were able to maintain esophageal patency during the 3-week follow-up and to reduce the infiltration of inflammatory cells and the amount of fibrous tissue. These results showed that the PTX-PLGA-coated Mg stent has the potential to be a safe and effective approach for benign esophageal stricture. Statement of significanceWe designed a biodegradable composite stent, having poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX) coated the surface of the magnesium (Mg)-based braided stent. We evaluated in vitro and in vivo characteristics of the Mg esophageal stent having a PLGA coating plus a variable concentration of PTX in comparison with the absence of PTX PLGA coating. The PTX PLGA stents exerted higher radial force than stents without coating, degraded more quickly in an acid medium, and effectively promoted fibroblast apoptosis in vitro experiments. In a rabbit model of caustic-induced esophageal stricture, there was an increased lumen and decreased inflammation of the esophageal wall in the animals stented with PTX-PLGA versus the sham group, indicating a potential approach for benign esophageal stricture.

Magnesium stents manufacturing: Experimental application of a novel hybrid thin-walled investment casting approach

The present study addresses a thin-walled investment casting methodology of AZ91D-1 wt% CaO magnesium alloy for stent manufacturing. Additive manufacturing and Yttria-based coating were applied to optimize the process. An induction melting furnace assisted by vacuum was used to cast magnesium alloy stents with 0.4 mm and 0.8 mm wall thickness under an argon-protective atmosphere. According to the proposed methodology and the results obtained for coated models, no metal-mould interface reactions were found, revealing samples with a good surface finish and sane microstructure. The cast magnesium stents without coating were compromised, resulting in samples with a high degree of reactions and impurities. Microscopic examination and hardness measurements demonstrated the effectiveness of the process.

Fatigue Properties of AZ31B Magnesium Alloy Processed by Equal-Channel Angular Pressing

A stent is employed to expand a narrowed tubular organ, such as a blood vessel. However, the persistent presence of a stainless steel stent yields several problems of late thrombosis, restenosis and chronic inflammation reactions. Biodegradable magnesium stents have been introduced to solve these problems. However, magnesium-based alloys suffer from poor ductility and lower than desired fatigue performance. There is still a huge demand for further research on new alloys and stent designs. Then, as fundamental research for this, AZ31 B magnesium alloy has been investigated for the effect of equal-channel angular pressing on the fatigue properties. ECAP was conducted for one pass and eight passes at 300 °C using a die with a channel angle of 90°. An annealed sample and ECAP sample of AZ31 B magnesium alloy were subjected to tensile and fatigue tests. As a result of the tensile test, strength in the ECAP (one pass) sample was higher than in the annealed sample. As a result of the fatigue test, at stress amplitude σa = 100 MPa, the number of cycles to failure was largest in the annealed sample, medium in the ECAP (one pass) sample and lowest in the ECAP (eight passes) sample. It was suggested that the small low cycle fatigue life of the ECAP (eight passes) sample is attributable to severe plastic deformation.

Bifunctional poly (l-lactic acid)/hydrophobic silica nanocomposite layer coated on magnesium stents for enhancing corrosion resistance and endothelial cell responses

Biodegradable magnesium (Mg)-based vascular stents can overcome the limitations of conventional permanent metallic stents, such as late in-stent restenosis and thrombosis, but still have difficulty retarding degradation while providing adequate mechanical support to the blood vessel. We incorporated silica nanoparticles surface-functionalized with hexadecyltrimethoxysilane (mSiNP) into a poly (l-lactic acid) (PLLA) coating as a physical barrier to disturb the penetration of the corrosive medium as well as a bioactive source that releases silicon ions capable of stimulating endothelial cells. The corrosion resistance and biocompatibility of this bifunctional PLLA/mSiNP nanocomposite coating were investigated using different weight ratios of mSiNP. The nanocomposite coating containing more than 10 wt% of the mSiNP (PLLA/10mSiNP and PLLA/20mSiNP) significantly delayed the corrosion of the Mg substrate and exhibited favorable endothelial cell responses, compared to the pure PLLA coating. Specifically, the calculated corrosion rates of PLLA/10mSiNP and PLLA/20mSiNP decreased by half, indicating the durability of the coating after immersion in simulated body fluid for 12 days. Based on the in vitro cellular response, the incorporation of the mSiNPs into the PLLA coating significantly improved the endothelial cell responses to the Mg substrate, showing better initial cell surface coverage, migration, and proliferation rate than those of pure PLLA. These results indicate that the PLLA/mSiNP nanocomposite coatings have significant potential to improve the corrosion resistance and vascular compatibility of biodegradable Mg-based vascular stents.

Estimation of Degradation Velocity of Biocompatible Damaged Stents due to Blood Flow.

Bioresorbable materials represent a promising technology for the treatment of coronary disease. Among the different materials employed, magnesium stents display favourable mechanical properties. One of the main uncertainties regarding use is their behaviour when deployed on coronary bifurcations, especially when their retardant coating has been damaged during the implantation process. This paper analyses the temporal evolution of the degradation of a damaged magnesium stent inserted into a coronary bifurcation. The rate of erosion-corrosion and the effect of the flow configuration on the mass transfer coefficient were estimated on the basis of previous experimental studies and numerical simulations. This coefficient has been employed to reproduce the conditions that can appear in real stent configurations, and computational fluid dynamics simulations were performed. The diffusion coefficient for this particular case has been calculated from the mass transfer coefficient and the Sherwood number. The results of the simulation show how the presence of the inner artery wall has a positive effect, preventing a premature degradation of the stent, and how the distal strut is protected by the presence of the proximal struts. This study demonstrates the usefulness of the proposed methodology to evaluate the temporal evolution of the degradation of struts made of magnesium alloys. In addition, this methodology can be applied to a study of different materials and geometric configurations. The proposed technique can contribute to expanding existing knowledge concerning bioresorbable stent flow-corrosion, thus improving their design and implantation.

Characterization of a Sandwich PLGA-Gallic Acid-PLGA Coating on Mg Alloy ZK60 for Bioresorbable Coronary Artery Stents.

Absorbable magnesium stents have become alternatives for treating restenosis owing to their better mechanical properties than those of bioabsorbable polymer stents. However, without modification, magnesium alloys cannot provide the proper degradation rate required to match the vascular reform speed. Gallic acid is a phenolic acid with attractive biological functions, including anti-inflammation, promotion of endothelial cell proliferation, and inhibition of smooth muscle cell growth. Thus, in the present work, a small-molecule eluting coating is designed using a sandwich-like configuration with a gallic acid layer enclosed between poly (d,l-lactide-co-glycolide) layers. This coating was deposited on ZK60 substrate, a magnesium alloy that is used to fabricate bioresorbable coronary artery stents. Electrochemical analysis showed that the corrosion rate of the specimen was ~2000 times lower than that of the bare counterpart. The released gallic acid molecules from sandwich coating inhibit oxidation by capturing free radicals, selectively promote the proliferation of endothelial cells, and inhibit smooth muscle cell growth. In a cell migration assay, sandwich coating delayed wound closure in smooth muscle cells. The sandwich coating not only improved the corrosion resistance but also promoted endothelialization, and it thus has great potential for the development of functional vascular stents that prevent late-stent restenosis.

OCT-guided complication management during sirolimus-eluting bioresorbable magnesium stent implantation with nine months OCT follow-up

Aims/Objectives: To study the feasibility, outcome of ULMPCI in a peripheral centre. Methods: 83 consecutive patients from February 2008 till September 2019 who underwent PCI of left main coronary were included in this study. Data of all these patients with regard to clinical presentation, procedural details and follow up was obtained. Syntax and Euroscore was calculated in all patients. Primary endpoint was MACCE (mortality, stroke, and revascularisation). Results: Mean age of the patients was 64.3 years, and majority of the patients presented with ACS 54(65%). Majority of patients had multiple risk factors 58(69.9%) and also renal failure 63(75.63%). Mean Syntax score was 23.61 and mean euroscore 36.04. A cumulative MACCE rate at the end of 5 years was 17/83(20.5%). Mean event-free survival was 7.2 years. Except Euroscore which predicted MACCE at 6 months no other parameters including Syntax score were predictive though lower syntax score had higher event free survival. Conclusion: PCI of left main coronary artery in challenging environment of a peripheral centre is feasible with comparable results and many times life saving

Impressive late stent recoil of a drug-eluting resorbable magnesium coronary stent

The coronary angiograms showed a severe focal restenosis of the resorbable magnesium stent previously implanted in the right coronary artery. Coronary intravascular ultrasound did not show any significant intraluminal proliferation but demonstrated an impressive late stent recoil.

Computational modelling of magnesium stent mechanical performance in a remodelling artery: Effects of multiple remodelling stimuli.

Significant research has been conducted in the area of coronary stents/scaffolds made from resorbable metallic and polymeric biomaterials. These next-generation bioabsorbable stents have the potential to completely revolutionise the treatment of coronary artery disease. The primary advantage of resorbable devices over permanent stents is their temporary presence which, from a theoretical point of view, means only a healed coronary artery will be left behind following degradation of the stent potentially eliminating long-term clinical problems associated with permanent stents. The healing of the artery following coronary stent/scaffold implantation is crucial for the long-term safety of these devices. Computational modelling can be used to evaluate the performance of complex stent devices in silico and assist in the design and development and understanding of the next-generation resorbable stents. What is lacking in computational modelling literature is the representation of the active response of the arterial tissue in the weeks and months following stent implantation, ie, neointimal remodelling, in particular for the case of biodegradable stents. In this paper, a computational modelling framework is developed, which accounts for two major physiological stimuli responsible for neointimal remodelling and combined with a magnesium corrosion model that is capable of simulating localised pitting (realistic) stent corrosion. The framework is used to simulate different neointimal growth patterns and to explore the effects the neointimal remodelling has on the mechanical performance (scaffolding support) of the bioabsorbable magnesium stent.

In vivo and in vitro evaluation of a biodegradable magnesium vascular stent designed by shape optimization strategy

The performance of biodegradable magnesium alloy stents (BMgS) requires special attention to non-uniform residual stress distribution and stress concentration, which can accelerate localized degradation after implantation. We now report on a novel concept in stent shape optimization using a finite element method (FEM) toolkit. A Mg-Nd-Zn-Zr alloy with uniform degradation behavior served as the basis of our BMgS. Comprehensive in vitro evaluations drove stent optimization, based on observed crimping and balloon inflation performance, measurement of radial strength, and stress condition validation via microarea-XRD. Moreover, a Rapamycin-eluting polymer coating was sprayed on the prototypical BMgS to improve the corrosion resistance and release anti-hyperplasia drugs. In vivo evaluation of the optimized coated BMgS was conducted in the iliac artery of New Zealand white rabbit with quantitative coronary angiography (QCA), optical coherence tomography (OCT) and micro-CT observation at 1, 3, 5-month follow-ups. Neither thrombus or early restenosis was observed, and the coated BMgS supported the vessel effectively prior to degradation and allowed for arterial healing thereafter.The proposed shape optimization framework based on FEM provides an novel concept in stent design and in-depth understanding of how deformation history affects the biomechanical performance of BMgS. Computational analysis tools can indeed promote the development of biodegradable magnesium stents.

Silicone-covered biodegradable magnesium stent for treating benign esophageal stricture in a rabbit model.

BACKGROUNDStent insertion can effective alleviate the symptoms of benign esophageal strictures (BES). Magnesium alloy stents are a good candidate because of biological safety, but show a poor corrosion resistance and a quick loss of mechanical support in vivo.AIMTo test the therapeutic and adverse effects of a silicone-covered magnesium alloy biodegradable esophageal stent.METHODSFifteen rabbits underwent silicone-covered biodegradable magnesium stent insertion into the benign esophageal stricture under fluoroscopic guidance (stent group). The wall reconstruction and tissue reaction of stenotic esophagus in the stent group were compared with those of six esophageal stricture models (control group). Esophagography was performed at 1, 2, and 3 weeks. Four, six, and five rabbits in the stent group and two rabbits in the control groups were euthanized, respectively, at each time point for histological examination.RESULTSAll stent insertions were well tolerated. The esophageal diameters at immediately, 1, 2 and 3 wk were 9.8 ± 0.3 mm, 9.7 ± 0.7 mm, 9.4 ± 0.8 mm, and 9.2 ± 0.5 mm, respectively (vs 4.9 ± 0.3 mm before stent insertion; P < 0.05). Magnesium stents migrated in eight rabbits [one at 1 wk (1/15), three at 2 wk (3/11), and four at 3 wk (4/5)]. Esophageal wall remodeling (thinner epithelial and smooth muscle layers) was found significantly thinner in the stent group than in the control group (P < 0.05). Esophageal injury and collagen deposition following stent insertion were similar and did not differ compared to rabbits with esophageal stricture and normal rabbits (P > 0.05).CONCLUSIONEsophageal silicone-covered biodegradable magnesium stent insertion is feasible for BES without causing severe injury or tissue reaction. Our study suggests that insertion of silicone-covered magnesium esophageal stent is a promising approach for treating BES.

The addition of silver affects the deformation mechanism of a twinning-induced plasticity steel: Potential for thinner degradable stents

While Fe-based alloys have already been reported to possess all mechanical properties required for vascular stenting, their relatively low degradation rate in vivo still constitutes their main bottleneck. The inflammatory reaction generated by a stent is inversely proportional to its mass. Therefore, the tendency in stenting is to lower the section so to reduce the inflammatory reaction. Twinning-induced plasticity steels (TWIP) possess excellent mechanical properties for envisaging the next generation of thinner degradable cardiovascular stents. To accelerate the degradation, the addition of noble elements was proposed, aimed at promoting corrosion by galvanic coupling. In this context, silver was reported to generally increase the degradation rate. However, its impact on the deformation mechanism of TWIP steels has not been reported yet. Results show that the use of Ag significantly reduces the ductility without altering the strength of the material. Furthermore, the presence of Ag was found to promote a different deformation texture, thus stimulating the formation of mechanical martensite. Since a stent works in the deformed state, understanding the microstructure and texture resulting from plastic deformation can effectively help to forecast the degradation mechanisms taking place during implantation and the expected degradation time. Moreover, knowing the deformed microstructure allows to understand the formability of very small tubes, as precursors of the next generation of thin section degradable stents. Statement of significanceCommercial degradable magnesium stents are limited from their relatively big structure size. Twinning-induced plasticity steels possess outstanding mechanical properties, but their degradation time goes beyond the timeframe expected from clinics. The inclusion of noble Ag particles, which favor galvanic coupling, is known to promote corrosion and solve this limitation. However, it is necessary to understand the impact that Ag has on the deformation microstructure and on the mechanical properties. The addition of Ag reduces the ductility of a twinning-induced plasticity steel because of a different deformation microstructure. Since a stent works in a deformed state inside an artery, understanding the microstructural evolution after plastic deformation allows to better predict the device performances during service life.

Modeling and Experimental Studies of Coating Delamination of Biodegradable Magnesium Alloy Cardiovascular Stents.

Biodegradable magnesium alloy stents exhibit deficient corrosion period for clinic applications, making the protective polymer coating more crucial than drug-eluting stents with the permanent metal scaffold. We implemented a cohesive method based on a finite element analysis method to predict the integrity of adhesive between coating and stent during the crimping and deployment. For the first time, the three-dimensional quantitative modeling reveals the process of polymer coating delamination and stress concentration. The fracture and microcracks of coatings were consistent with the simulation result, confirmed by the scanning electron microscopy observation. Moreover, we analyzed four possible factors, i.e., stent design, strut material, coating polymer, and thickness of the coating, affecting the stent-coating damage and the distribution of the stress in coatings. Mg-Nd-Zn-Zr alloy with lower yield strength performed a more uniform strain distribution and more favorable adhesion of the coating than the commercial magnesium alloy AZ31. Shape optimization of stent design improves the strain and stress distribution of coating remarkably, avoiding coating delamination. Additionally, PLGA coating with lower elastic modulus and yield strength tends to follow the deformation of the stent better and to adhere on the surface more tightly, compared to PLLA polymer. A reduction in coating thickness and an increase in the strength of stent-coating interface improve the resistance to delamination. Our framework based on cohesive method provides an in-depth understanding of stent-coating damage and shows the way of computational analyses could be implemented in the design of coated biodegradable magnesium stents.

The effect of tensile and fluid shear stress on the in vitro degradation of magnesium alloy for stent applications

Magnesium alloys have gained great attention as biodegradable materials for stent applications. Cardiovascular stents are continuously exposed to different types of mechanical loadings simultaneously during service, including tensile, compressive and fluid shear stress. In this study, the in vitro degradation of WE43 wires was investigated under combined effect of tensile loading and fluid shear stress and compared with that experienced an individual loading condition. For the individual mechanical loading treatment, the degradation of magnesium wires was more severely affected by tensile loading than fluid shear stress. Under tensile loading, magnesium wires showed faster increment of corrosion rates, loss of mechanical properties and localized corrosion morphology with the increasing tensile loadings. With the combined stress, smaller variation of the corrosion rates as well as the slower strength degeneration was shown with increasing stress levels, in comparison with the individual treatment of tensile loading. This study could help to understand the effect of complex stress condition on the corrosion of magnesium for the optimization of biodegradable magnesium stents.

Shape and functional optimization of biodegradable magnesium stents for manufacturing by ultrasonic-microcasting technique

In this study, a well-known stent model, Palmaz–Schatz, and a new geometry, NG, are optimized, in agreement with a set of optimization variables and limiting values of the design parameters, imposed by a new manufacturing process—ultrasonic-microcasting—, which allows to surpass some difficulties presented by other manufacturing technologies. The optimized designs shown that significantly lower values of the considered performance parameters can be obtained, namely in terms of required expansion pressure, which was reduced 30.31% for Palmaz–Schatz stent and 55% for NG stent. Dogboning and foreshortening were minimized and a reduction of 97.30 and 86.64%, respectively, was achieved for Palmaz–Schatz model, while for NG model such values were 13.64 and 50.00%. Despite the greater values of thickness comparing to the stainless-steel devices (0.30 vs 0.10 mm), the optimized stents studied present a similar or even better performance than those. Furthermore, results suggest that the adopted optimization methodology can effectively optimize the stent’s design and their functionality for devices to be manufacturing by the ultrasonic-microcasting processing. The presented optimization methodology allows the interaction between the requirements imposed by the patient’s condition, i.e. the initial and expanded diameter of the stent and its length, and the constraints imposed by the manufacturing process, having as result the optimal geometry regarding the defined objectives.