Biodegradable Magnesium Alloy Stents Research Articles

Fucoidan-based coating on magnesium alloy improves the hemocompatibility and pro-endothelialization potential for vascular stent application

Biodegradable magnesium alloy stents have great application potential in the treatment of cardiovascular diseases. However, bare magnesium alloy stents are still limited by some problems such as too fast degradation, poor hemocompatibility, and inability to regulate the behaviors of vascular cells in clinical applications. Surface modifications are highly requested to improve the corrosion resistance and biocompatibility of magnesium alloy stents. Herein, a fucoidan-based coating consisting of MgF2 layer, polydopamine (PDA) and fucoidan was constructed on Mg-Zn-Y-Nd (ZE21B) alloy to improve its corrosion resistance, hemocompatibility and rapid endothelialization for vascular stent application. Compared to bare ZE21B alloy, the modified ZE21B alloy exhibited better corrosion resistance and hemocompatibility. More importantly, the endothelial cells (ECs) and smooth muscle cells (SMCs) exhibited a distinct dose-dependent behaviors towards the fucoidan grafting density. The relatively low fucoidan grafting density promoted the proliferation, spreading and migration of ECs, but suppressed these behaviors of SMCs. The results of in vivo implantation experiments indicated that the fucoidan-based coating modified ZE21B alloy can inhibit intimal hyperplasia, relieve tissue inflammation, and promote the rapid endothelialization. Thus, the fucoidan-based coating provides a simple and effective strategy to develop novel magnesium alloy stents with improved corrosion resistance, good hemocompatibility and pro-endothelialization potential.

Enhanced corrosion resistance and biocompatibility of an elastic poly (butyleneadipate-co-terephthalate) composite coating for AZ31 magnesium alloy vascular stents

Surface modification has been considered to provide an effective solution to the poor corrosion resistance of magnesium alloys. A large number of relevant studies have demonstrated that various protective coatings can reduce the degradation rate of magnesium alloys, but most of them are for magnesium alloy materials and devices without deformation. For biodegradable magnesium alloy stents, the selection of protective coating is vitally important due to the residual stress during implantation and cyclic loading after implantation. Therefore, compared with commonly used poly-D,l-lactide (PDLLA), a reliable protection was proposed on HF-treated Mg alloy via application of poly(butyleneadipate-co-terephthalate) (PBAT) with high elongation at break in this paper. In the long term, the corrosion resistance of PBAT-F coating of both flake samples and stents was decisively superior to PDLLA, which could be attributed to its outstanding barrier performance and mechanical properties. Simultaneously, PBAT composite coating exhibited better hemocompatibility and higher cell proliferation rates. The above results show that PBAT is an excellent coating material for vascular stents whereas PBAT composite coating could be a promising candidate as a protective coating for Mg stents.

Preparation of functional coating on magnesium alloy with hydrophilic polymers and bioactive peptides for improved corrosion resistance and biocompatibility

• A multifunctional coating was constructed on ZE21B alloy for biodegradable vascular stents. • MgF 2 layer and hydrophilic polymers in the functional coating could effectively protect ZE21B alloy from overfast degradation. • Anticoagulant ACH 11 peptides and ECs-selective REDV peptides in the functional coating could dramatically enhance the hemocompatibility and pro-endothelialization capacity of ZE21B alloy. • The functional coating systematically improved the corrosion resistance and biocompatibility of ZE21B alloy in vitro and in vivo . Biodegradable magnesium alloy stents (MAS) have great potential in the treatment of cardiovascular diseases. However, too fast degradation and the poor biocompatibility are still two key problems for the clinical utility of MAS. In the present work, a functional coating composed of hydrophilic polymers and bioactive peptides was constructed on magnesium alloy to improve its corrosion resistance and biocompatibility in vitro and in vivo . Mg-Zn-Y-Nd (ZE21B) alloy modified with the functional coating exhibited moderate surface hydrophilicity and enhanced corrosion resistance. The favourable hemocompatibility of ZE21B alloy with the functional coating was confirmed by the in vitro blood experiments. Moreover, the modified ZE21B alloy could selectively promote the adhesion, proliferation, and migration of endothelial cells (ECs), but suppress these behaviors of smooth muscle cells (SMCs). Furthermore, the modified ZE21B alloy wires could alleviate intimal hyperplasia, enhance corrosion resistance and re-endothelialization in vivo transplantation experiment. These results collectively demonstrated that the functional coating improved the corrosion resistance and biocompatibility of ZE21B alloy. This functional coating provides new insight into the design and development of novel biodegradable stents for biomedical engineering.

Optimizing structural design on biodegradable magnesium alloy vascular stent for reducing strut thickness and raising radial strength

Thinner biodegradable magnesium alloy stents (BMgSs) afford faster endothelialisation to delay degradation and better clinical performance. However, compared with traditional non-degradable stents, thin-walled BMgS structures are prone to challenges, such as insufficient support capacity and fracture, during immediate expansion due to low elastic modulus and ultimate elongation. In this study, a thin-walled BMgS structure was optimised. A ZE21B alloy with large breaking elongation and excellent mechanical properties served as the basis of our BMgS. Using finite element analysis, the support ring structure of a typical stent BioMatrix was optimised using response surface models, and an optimised configuration of a thin-walled BMgS was obtained. The optimised thin-walled stent (100-μm thick) had a radial strength comparable to that of the original thick-walled stent (150-μm thick); and the maximum principal strain is significantly decreased (0.207 vs 0.283). The balloon dilation and radial strength tests were validated. Experiments showed that the optimised stent had sufficient deformation stability during the crimping and expansion processes, and there was no strut fracture. Furthermore, the maximum principal stress area of the stent and the damage to the stenotic artery were significantly improved after optimisation.

Synthesis of Star 6-Arm Polyethylene Glycol-Heparin Copolymer to Construct Anticorrosive and Biocompatible Coating on Magnesium Alloy Surface.

Magnesium alloy has become a research hotspot of the degradable vascular stent materials due to its biodegradability and excellent mechanical properties. However, its rapid degradation rate after implantation and the limited biocompatibility restrict its application in clinic. Constructing a multifunctional bioactive polymer coating on the magnesium alloys represents one of the popular and effective approaches to simultaneously improve the corrosion resistance and biocompatibility. In the present study, the copolymer of 6-arm polyethylene glycol and heparin (PEG-Hep) was successfully synthesized and then immobilized on the surface of chitosan (Chi)-modified magnesium alloy surface through electrostatic interaction to improve the corrosion resistance and biocompatibility. The results of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy showed that a dense and compact coating was created on the magnesium alloy surface. The coating displayed excellent hydrophilicity. At the same time, the as-prepared coating can significantly not only improve the corrosion potential, reduce the corrosion current and the pH changes of the immersion solution, but also keep a relatively intact surface morphology after immersing in simulated body fluid solution for 14 days, demonstrating that the coating can significantly improve the corrosion resistance of the magnesium alloy. Moreover, the magnesium alloy with PEG-Hep coating exhibited excellent hemocompatibility according to the results of the hemolysis rate and platelet adhesion and activation. In addition, the modified magnesium alloy had a good ability to promote the endothelial cell adhesion and proliferation. Therefore, the PEG-Hep multifunctional coating can be applied in the surface modification of the biodegradable magnesium alloy stent to simultaneously improve the corrosion resistance and biocompatibility.

A biodegradable magnesium alloy vascular stent structure: Design, optimisation and evaluation

The existing biodegradable magnesium alloy stent (BMgS) structure is prone to problems, such as insufficient support capacity and early fracture at areas of concentrated stress. Herein, a stent structural design, which reduced the cross section of the traditional sin-wave stent by nearly 30% and introduces a regular arc structure in the middle of the support ring. The influence of the dual-parameter design of bending radius (r) and ring length (L) on plastic deformation, expansion and compression resistance performances are discussed. The non-dominated sorting genetic algorithm II (NSGA-II) was used to search for the optimal solution. It was found that the introduction of parameter r effectively improved the plastic deformation and expansion performance, and the reduction of L improved stent compression resistance. Finally, an optimized stent configuration was obtained. In vitro mechanical tests, including balloon inflation, radial strength and flexibility, verified the simulation results. The radial strength for the optimised stent increases by approximately 40% compared with that for the sinusoidal stent. Microarea X-ray diffraction result shows that the circumferential residual stress for the optimised stent decreases by half compared with that for the sinusoidal stent, thus effectively reducing the stress concentration phenomenon. Statement of significanceDespite current progress in BMgS research, the optimal design of the structure is limited. We present a new type of structurally designed stent. The performance of this stent was analysed by a finite element method and experimentally verified. The structural design positively influenced stent performance.

Subjective approach to optimal cross-sectional design of biodegradable magnesium alloy stent undergoing heterogeneous corrosion

Existing biodegradable Magnesium Alloy Stents (MAS) have several drawbacks, such as high restenosis, hasty degradation, and bulky cross-section, that limit their widespread application in a current clinical practice. To find the optimum stent with the smallest possible cross-section and adequate scaffolding ability, a 3D finite element model of 25 MAS stents of different cross-sectional dimensions were analysed while localized corrosion was underway. For the stent geometric design, a generic sine-wave ring of biodegradable magnesium alloy (AZ31) was selected. Previous studies have shown that the long-term performance of MAS was characterized by two key features: Stent Recoil Percent (SRP) and Stent Radial Stiffness (SRS). In this research, the variation with time of these two features during the corrosion phase was monitored for the 25 stents. To find the optimum profile design of the stent subjectively (without using optimization codes and with much less computational costs), radial recoil was limited to 27 % (corresponding to about 10 % probability of in-stent diameter stenosis after an almost complete degradation) and the stent with the highest radial stiffness was selected.The comparison of the recoil performance of 25 stents during the heterogeneous corrosion phase showed that four stents would satisfy the recoil criterion and among these four, the one having a width of 0.161 mm and a thickness of 0.110 mm, showed a 24 % – 49 % higher radial stiffness at the end of the corrosion phase. Accordingly, this stent, which also showed a 23.28 % mass loss, was selected as the optimum choice and it has a thinner cross-sectional profile than commercially available MAS, which leads to a greater deliverability and lower rates of restenosis.

Damage evolution of biodegradable magnesium alloy stent based on configurational forces

Magnesium alloy has attracted most of the recent attention as a candidate for stent material due to their biocompatible and biodegradable nature. However, their corrosion behavior in the human body is still a major issue in research today. In this paper, a strategy to simulate damage evolution in biodegradable magnesium alloy stent is given by introducing a configurational damage model. In the framework of continuum thermodynamics, one can characterize the development and evolution of local damage of materials by establishing internal variables in phenomenological method. We believe that corrosion can damage alloy in two different ways: surface corrosion and stress corrosion. Surface corrosion is described using uniform damage, when the structure is exposed in a corrosion environment; Configurational force is used to describe stress corrosion when the structure is exposed in a stimulating environment. We then select global damage and radial resistance force to perform the changes of macroscopic mechanical properties during stent degradation. Finally, the well performance of the proposed model is demonstrated through several numerical examples. This model has the potential to assist stent design and development in the future.

Computational Modeling of the Corrosion Process and Mechanical Performance of Biodegradable Stent

Magnesium alloy stents have drawn increasing research interest in recent years owing to their biodegradable behaviors. As dissolved by corrosion, mass of the magnesium alloy stents decreases with time, allowing mechanical load to gradually transfer to the surrounding tissues. This work aimed to develop a numerical model based on Continuum Damage Mechanics (CDM) combining pitting corrosion and stress corrosion crack to better predict the degradation behavior of biodegradable magnesium alloy stent. It was applied in coronary stents through finite element method compared with the use of single pitting corrosion model. The results indicated that addition of stress corrosion attack accelerated the degradation rate and support performance loss of stent compared with single pitting corrosion. The proposed model would bring new sights to simulation and serve the design of magnesium alloy stents.

Cellular response of biodegradable AZ31 magnesium alloy stent in artery

Because of the increasing incidence of coronary artery disease, the use of cardiovascular stents is gradually increasing. In percutaneous coronary intervention, advantage of bioresorbable stent is that the stent does not remain in the human body after completing the necessary mechanical support to ensure the blood vessel open, and finally degrades into harmless molecules. Compared with bare stents, which require long-term retention in the body, the incidence of restenosis in stent or late stent thrombosis was lower. Current biodegradable stent mainly include polymers, biodegradable stents and metal alloy stent. Magnesium-based stent degradation and its copolymers are used in the application of biological absorbable stents and attract the attention of researchers.

A Mini Review on Biodegradable Magnesium Alloy Vascular Stent

Biodegradable magnesium alloy stents are a new generation of vascular stents which can open up blocked blood vessels at an early stage, then degrade and be absorbed by the body at a suitable rate after the vascular has been repaired. Mg alloys are excellent materials for vascular stents benefit from their sufficient mechanical properties and good biocompatibility. At present, Mg alloy is also used as a green material in the research of vascular stents due to its biodegradable property. In this paper, based on the research situation of degradable Mg alloy stents in recent years, the research history, degradation mechanism, structural design and basic research experiments of Mg alloy stents are reviewed.

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.

Biodegradable Magnesium Alloy Stents as a Treatment for Vein Graft Restenosis.

PurposeTo explore the effects of biodegradable magnesium alloy stents (BMAS) on remodeling of vein graft (VG) anastomotic restenosis.Materials and MethodsTo establish a VG restenosis model, seventy two New Zealand rabbits were randomly divided into three groups according to whether a stent was implanted in the graft vein or not. BMASs and 316L stainless steel stents were implanted in BMAS and 316L groups, respectively, while no stent was implanted in the no-treatment control group (NC group). Loss of lumen diameter in the graft vein was measured in all three groups. Upon harvesting VG segments to evaluate intimal proliferation and re-endothelization, the degradation and biological safety of the stents were observed to explore the effects of BMAS on VG remodeling.ResultsModel establishment and stent implantation were successful. The BMAS reduced lumen loss, compared with the control group (0.05±0.34 mm vs. 0.90±0.39 mm, p=0.001), in the early stage. The neointimal area was smaller in the BMAS group than the 316L group after 4 months (4.96±0.66 mm2 vs. 6.80±0.69 mm2, p=0.017). Re-endothelialization in the BMAS group was better than that in the 316L group (p=0.001). Within 4 months, the BMAS had degraded, and the magnesium was converted to phosphorus and calcium. The support force of the BMAS began to reduce at 2–3 months after implantation, without significant toxic effects.ConclusionBMAS promotes positive remodeling of VG anastomosis and has advantages over the conventional 316L stents in the treatment of venous diseases.

Surface finishing of biodegradable stents

The surface conditions of stents influence their polymer/drug coatability, rate of degradation, and ultimately their mechanical strength, ability to expand, and service lifetime. This paper describes new polishing tools developed to mechanically polish entire biodegradable magnesium-alloy stents. Use of the new tools removes material from the peaks of the stent surfaces and enables surface smoothing equivalent to electrolytic polishing (EP) but with less material removal, helping extend the stent service life. Static immersion tests using Dulbecco’s modification of Eagle medium solution demonstrated that stents polished using the new tools had a rate of degradation about 40% lower than EP-processed stents.

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.

Mechanical and Corrosion Testing of Magnesium WE43 Specimens for Pitting Corrosion Model Calibration

Computational modeling can play an important role in the analysis, design, and development of complex medical devices such as biodegradable coronary stents. In this study, experimental mechanical and corrosion testing is conducted to characterize the mechanical and corrosion behavior of magnesium WE43 alloy, a candidate base material for biodegradable magnesium alloy stents. Previously developed uniform and pitting corrosion models are calibrated based on in vitro mechanical and corrosion testing of magnesium WE43 alloy specimens. The calibrated pitting corrosion model can capture the mechanical and corrosion behavior of magnesium WE43, including the experimentally observed non‐linear reduction in failure strength with mass loss, whereas the uniform corrosion model is incapable of capturing this trend. The calibrated corrosion models will be used in future research on magnesium alloy stents.

Process of the degradation in vivo and biosafety of biodegradable magnesium alloy stent

Objective: To observe the degradation process of biodegradable magnesium alloy stent (BMAS) in vivo in order to evaluate its degradation time and biological safety. Methods: Twenty-four male New Zealand white rabbits were divided into two groups: group A (n=12) and group B (n=12). The BMAS (a total of 12) was implanted in the infrarenal aorta of each rabbit in group A, while group B was the control group, without treatment. Color Doppler ultrasound was used at the 1, 2, 3, 4 months postoperatively to observe the degradation process of stents in group A. The arterial blood samples and main organs of two groups were also collected for biochemical examination and biosafety. Degradation assessment included transmission X-ray tomography (XRT), scanning electron microscope (SEM) and energy dispersion spectrum (EDS). Results: The XRT showed that the morphology of the stent was basically intact at 1 month after implantation, then scaffold composites were gradually degraded and absorbed. Degradation was basically completed at 4 months after operation. The early degradation products were Mg(2+) , then gradually replaced by Ca(2+) , P and other inorganic composition. There was no obvious adverse reactions in group A during the 4 months follow-up period. There was no statistical difference between the two groups in blood biochemical and pathological results (all P>0.05). Conclusion: BMAS can be degraded within 4 months in the abdominal aorta of rabbit, and the main degradation products are Ca(2+) and P, with good biosafety.

Research on Endothelial Cytocompatibility of Magnesium Alloy

In-stent restenosis is a main problem in the application of stents. It has been proved that rapid endothelialization of stents after implantation is the key point for solving the problem of restenosis. Recent years researchers focus on developing biodegradable magnesium alloy stents. The cytocompatibility is essential for the design of magnesium alloy stents. In this article, recent research about the endothelial cytocompatibility of magnesium alloy was reviewed, including methods, results, shortcomings and advice.

Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review

Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept "bio-adaption" between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed.

Effectiveness of Biodegradable Magnesium Alloy Stents in Coronary Artery and Femoral Artery.

To access the biocompatibility, effectiveness, and safety of biodegradable magnesium (Mg) alloy stent (BMAS) in the coronary artery and femoral artery. Atherosclerosis is a lesion of cardiovascular system, including the diseases in heart and blood vessels. The aluminum (Al) and zinc (Zn)-based BMAS was designed by cold drawing methods. Forty healthy immunized mongrel dogs were randomly divided into 8 groups. Five dogs who have not been treated with stent were included in control group. The other dogs were implanted with an absorbable magnesium (Mg) alloy in the coronary and/or femoral artery, and their artery angiography were observed at 7 time points (1, 3, 5, 7, 14, 21, and 28 days; n = 5) follow-up. Dogs from each cohort were sacrificed following angiography for pathology assessment. The histological response including inflammatory response, thrombosis, and intimal hyperplasia were analyzed by hematoxylin-eosin staining. Lumen area (La), intimal hyperplasia area (IHa), and the ratio of IHa were calculated by image analysis software. The thin-walled BMAS were designed and produced by cold-drawing technology. Fifty-one devices were implanted into coronary artery of 35 dogs successfully. During the follow-up days, the angiography of coronary artery and femoral artery had confirmed that the lumen was clear and there were no elastic recoil and thrombosis. The stents were completely disappeared at 7 days after implantation. Moderate intimal hyperplasia was found at 14 days after implantation. The BMAS stent proved to be of good biocompatibility, safety, and effectiveness. (J Interven Cardiol 2015;XXXX:XX-XX).