Biodegradable Magnesium Alloy Stents Research Articles

Modeling and Experimental Studies of Peeling of Polymer Coating for Biodegradable Magnesium Alloy Stents

Abstract Biodegradable magnesium alloy stents (MAS) could improve the long-term clinical results of commercial bare metal or drug-eluting stents. MAS have shown a limited mechanical support for diseased vessels due to fast degradation. Protective polymer coating is a reasonable way to reduce the degradation rate of MAS. However, peeling of the coating during stent expansion is the main obstacle in stent application. In this study, experimental and computational methods were used to study the peeling problem of an optimized MAS design. The 90° peeling test provided the critical energy release rate with cohesive zone method to be used in the simulation study; the 90° peeling modeling had good agreement with the experimental test. Using reliable cohesive element material parameters, the simulation could verify whether the peeling happened when the coated MAS was expanded. The aim of this study is to provide an easy and reliable method to approach peeling problem of MAS, giving the instructions for the improvement of MAS coatings.

Hemolysis and cytotoxicity mechanisms of biodegradable magnesium and its alloys

Good hemocompatibility and cell compatibility are essential requirements for coronary stents, especially for biodegradable magnesium alloy stents, which could change the in situ environment after implanted. In this work, the effects of magnesium ion concentration and pH value on the hemolysis and cytotoxicity have been evaluated. Solution with different Mg2+ concentration gradients and pH values of normal saline and cell culture media DMEM adjusted by MgCl2 and NaOH respectively were tested for the hemolysis and cell viability. Results show that even when the concentration of Mg2+ reaches 1000μg/mL, it has little destructive effect on erythrocyte, and the high pH value over 11 caused by the degradation is the real reason for the high hemolysis ratio. Low concentrations of Mg2+ (<100μg/mL) cause no cytotoxicity to L929 cells, of which the cell viability is above 80%, while high concentrations of Mg2+ (>300μg/mL) could induce obvious death of the L929 cells. The pH of the extract plays a synergetic effect on cytotoxicity, due to the buffer action of the cell culture medium. To validate this conclusion, commercial pure Mg using normal saline and PBS as extract was tested with the measurement of pH and Mg2+ concentration. Pure Mg leads to a higher hemolysis ratio in normal saline (47.76%) than in buffered solution (4.38%) with different pH values and low concentration of Mg2+. The Mg extract culture media caused no cytotoxicity, with pH=8.44 and 47.80μg/mLMg2+. It is suggested that buffered solution and dynamic condition should be adopted in the hemolysis evaluation.

Development of biodegradable magnesium alloy stents with coating

Biodegradable stents are attracting the attention of many researchers in biomedical and materials research fields since they can absolve their specific function for the expected period of time and then gradually disappear. This feature allows avoiding the risk of long-term complications such as restenosis or mechanical instability of the device when the vessel grows in size in pediatric patients. Up to now biodegradable stents made of polymers or magnesium alloys have been proposed. However, both the solutions have limitations. The polymers have low mechanical properties, which lead to devices that cannot withstand the natural contraction of the blood vessel: the restenosis appears just after the implant, and can be ascribed to the compliance of the stent. The magnesium alloys have much higher mechanical properties, but they dissolve too fast in the human body. In this work we present some results of an ongoing study aiming to the development of biodegradable stents made of a magnesium alloy that is coated with a polymer having a high corrosion resistance. The mechanical action on the blood vessel is given by the magnesium stent for the desired period, being the stent protected against fast corrosion by the coating. The coating will dissolve in a longer term, thus delaying the exposition of the magnesium stent to the corrosive environment. We dealt with the problem exploiting the potentialities of a combined approach of experimental and computational methods (both standard and ad-hoc developed) for designing magnesium alloy, coating and scaffold geometry from different points of views. Our study required the following steps: i) selection of a Mg alloy suitable for stent production, having sufficient strength and elongation capability; ii) computational optimization of the stent geometry to minimize stress and strain after stent deployment, improve scaffolding ability and corrosion resistance; iii) development of a numerical model for studying stent degradation to support the selection of the best geometry; iv) optimization of the alloy microstructure and production of Mg alloy tubes for stent manufacturing; v) set up, in terms of laser cut and surface finishing, of the procedure to manufacture magnesium stents; vi) selection of a coating able to assure enough corrosion resistance and computational evaluation of the coating adhesion. In the paper the multi-disciplinary approach used to go through the steps above is summarized. The obtained results suggest that developed methodology is effective at designing innovative biomedical devices.

Simulation study on uneven expansion behaviour of biodegradable magnesium alloy stents by finite element analysis

Biodegradable magnesium alloy stents (MAS) provide a temporary opening to a diseased coronary vessel until the vessel finishes the remodelling, and then the stents disappear progressively to avoid the long term incompatible interaction between the vessel and the stents. Biodegradability makes the magnesium alloys to be an ideal candidate as a generation stent material. However, the inferior mechanical properties of the magnesium alloys limit the design of MAS. In the present study, the uneven expansion behaviour of MAS was investigated through the finite element analysis method. The results showed that the uneven expansion behaviours of MAS originated from the relationship between the balloon flaps and the stent meshes. This study provides a theoretical reference for stent design and selection of the expansion method.

POLYMER IODINATION FOR IMPROVED IN VITRO TRACKING OF BIODEGRADABLE STENT DEGRADATION: SERIAL MICROCT IMAGING FOR BIOREACTOR TESTING

Evaluating the in vitro degradation of a biodegradable magnesium (Mg) alloy stent by X-ray micro-computed tomography (CT) is made difficult by low attenuation of Mg and polymer coating. Addition of iodine (I) to polymer coating of Mg stents was investigated to improve segmentation of microCT images

Experimental data confirm numerical modeling of the degradation process of magnesium alloys stents

Biodegradable magnesium alloy stents (MAS) could present improved long-term clinical performances over commercial bare metal or drug-eluting stents. However, MAS were found to show limited mechanical support for diseased vessels due to fast degradation. Optimizing stent design through finite element analysis (FEA) is an efficient way to improve such properties. Following previous FEA works on design optimization and degradation modeling of MAS, this work carried out an experimental validation for the developed FEA model, thus proving its practical applicability of simulating MAS degradation. Twelve stent samples of AZ31B were manufactured according to two MAS designs (an optimized one and a conventional one), with six samples of each design. All the samples were balloon expanded and subsequently immersed in D-Hanks’ solution for a degradation test lasting 14days. The experimental results showed that the samples of the optimized design had better corrosion resistance than those of the conventional design. Furthermore, the degradation process of the samples was dominated by uniform and stress corrosion. With the good match between the simulation and the experimental results, the work shows that the FEA numerical modeling constitutes an effective tool for design and thus the improvement of novel biodegradable MAS.

Magnesium Alloy Stent Expansion Behavior Simulated by Finite Element Method

Biodegradable magnesium alloy stents have gained increasing interest in the past years due to their potential prospect. Magnesium alloy is brittle compared with stainless steel. This means it has less elongation than other stent materials and it may cause strut break under large deformation. In this paper, a finite element model for magnesium alloy stent is studied to simulate the mechanical behavior of the stent. It is composed of 1.5mm in inner diameter, 7mm length, 80µm thickness and 110µm in cross-sectional width. Six mechanical properties have been studied by mathematical modeling with determination of: (1) stent deployment pressure; (2) the intrinsic elastic recoil of the material used; (3) the stent foreshortening; (4) the stent coverage area, (5) the stent flexibility; and (6) the stress maps.

EXPERIMENTAL VERIFICATION OF OPTIMIZATION AND DEGRADATION SIMULATION OF MAGNESIUM ALLOY STENT

Biodegradable magnesium alloy stents (MAS) can avoid long-term incompatibility between vessels and permanent stent platforms. To increase the insufficient scaffolding of existing MAS, finite element analysis (FEA) was carried to provide an optimized MAS design [Wu, 2010]. Corrosion resistance of three MAS designs were compared using a biodegradable material model [Gastaldi, 2011; Wu, 2011]. Results showed that the optimized design (Stent B) has the best resistance although a patent design (Stent C) has more material (Figure 1). Experimental tests are needed to verify that optimization can improve the corrosion resistance and that the biodegradable stent modelling can follow the corrosion mechanism of the MAS after balloon expansion.

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. (C) 2011 Elsevier B.V. All rights reserved.

Finite Element Shape Optimization for Biodegradable Magnesium Alloy Stents

Biodegradable magnesium alloy stents (MAS) are a promising solution for long-term adverse events caused by interactions between vessels and permanent stent platforms of drug eluting stents. However, the existing MAS showed severe lumen loss after a few months: too short degradation time may be the main reason for this drawback. In this study, a new design concept of MAS was proposed and a shape optimization method with finite element analysis was applied on two-dimensional (2D) stent models considering four different magnesium alloys: AZ80, AZ31, ZM21, and WE43. A morphing procedure was utilized to facilitate the optimization. Two experiments were carried out for a preliminary validation of the 2D models with good results. The optimized designs were compared to an existing MAS by means of three-dimensional finite element analysis. The results showed that the final optimized design with alloy WE43, compared to the existing MAS, has an increased strut width by approximately 48%, improved safety properties (decreased the maximum principal stress after recoil with tissue by 29%, and decreased the maximum principal strain during expansion by 14%) and improved scaffolding ability (increased by 24%). Accordingly, the degradation time can be expected to extend. The used methodology provides a convenient and practical way to develop novel MAS designs.

Short‐Term Effects of Biocorrodible Iron Stents in Porcine Coronary Arteries

Biocorrodible iron stents carry the potential to overcome limitations, such as chronic inflammation and premature recoil, posed by biodegradable polymer and magnesium alloy stents. This study aimed to test the safety and efficacy of biocorrodible iron stents in porcine coronary arteries. Iron stents and cobalt chromium stents were randomly deployed in the coronary arteries of juvenile domestic pigs. Animals were sacrificed at 28 days, and the vessels were fixed and processed for histochemistry. At 28 days, iron stents started to show signs of degradation without evidence of stent particle embolization or thrombosis without traces of excess inflammation, or fibrin deposition. At 28 days, the surface of the iron stent struts was black to brown and the vascular wall adjacent to the iron stent had a brownish tinge. There were no statistically significant differences in any of the measured parameters between segments implanted with iron and cobalt chromium stents. There were also no adverse effects in the persistent areas. The current study demonstrates that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents.

Late adaptive coronary artery remodelling after implantation of a biodegradable stent

Stenting with biodegradable stents is a new interventional approach aimed at adaptive coronary remodelling by limiting acute elastic recoil and late neointimal proliferation. Here, we report on a 53-year-old patient...