Magnesium Stents Research Articles

Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable experimental animal models to test novel embolization materials such as stents and flow diverters. The aim of the present project was to design a safe, fast, and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model. Saccular aneurysms were created from an arterial graft from the descending aorta.The aneurysms were microsurgically transplanted through end-to-side anastomosis to the infrarenal abdominal aorta of a syngenic male Wistar rat weighing >500 g. Following aneurysm anastomosis, aneurysm embolization was performed using balloon expandable magnesium stents (2.5 mm x 6 mm). The stent system was retrograde introduced from the lower abdominal aorta using a modified Seldinger technique. Following a pilot series of 6 animals, a total of 67 rats were operated according to established standard operating procedures. Mean surgery time, mean anastomosis time, and mean suturing time of the artery puncture site were 167 ± 22 min, 26 ± 6 min and 11 ± 5 min, respectively. The mortality rate was 6% (n=4). The morbidity rate was 7.5% (n=5), and in-stent thrombosis was found in 4 cases (n=2 early, n=2 late in stent thrombosis). The results demonstrate the feasibility of standardized stent occlusion of saccular sidewall aneurysms in rats - with low rates of morbidity and mortality. This stent embolization procedure combines the opportunity to study novel concepts of stent or flow diverter based devices as well as the molecular aspects of healing.

Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique.

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable experimental animal models to test novel embolization materials such as stents and flow diverters. The aim of the present project was to design a safe, fast, and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model. Saccular aneurysms were created from an arterial graft from the descending aorta.The aneurysms were microsurgically transplanted through end-to-side anastomosis to the infrarenal abdominal aorta of a syngenic male Wistar rat weighing >500 g. Following aneurysm anastomosis, aneurysm embolization was performed using balloon expandable magnesium stents (2.5 mm x 6 mm). The stent system was retrograde introduced from the lower abdominal aorta using a modified Seldinger technique. Following a pilot series of 6 animals, a total of 67 rats were operated according to established standard operating procedures. Mean surgery time, mean anastomosis time, and mean suturing time of the artery puncture site were 167 ± 22 min, 26 ± 6 min and 11 ± 5 min, respectively. The mortality rate was 6% (n=4). The morbidity rate was 7.5% (n=5), and in-stent thrombosis was found in 4 cases (n=2 early, n=2 late in stent thrombosis). The results demonstrate the feasibility of standardized stent occlusion of saccular sidewall aneurysms in rats - with low rates of morbidity and mortality. This stent embolization procedure combines the opportunity to study novel concepts of stent or flow diverter based devices as well as the molecular aspects of healing.

TCT-370 Comparison of Acute Thrombogenicity for Magnesium vs Stainless Steel Stents in a Porcine Arteriovenous Shunt Model

TCT-370 Comparison of Acute Thrombogenicity for Magnesium vs Stainless Steel Stents in a Porcine Arteriovenous Shunt Model

Improve blood compatibility of bioresorbable magnesium stents coated with functionalized anti-CD34 antibody and heparin-collagen multiplayers.

Instentrestenosis and late stent thrombosis continue to be the greatest limitations of drug-eluting stents. In this study, an anti-CD34 antibody functionalized multilayer of heparin/collagen type I is developed by layer-by-layer assemble to enhance biocompatibility and recruit endothelial progenitor cells. The SEM results demonstrate that (Hep/Col)5-coated samples have a rougher surface compared to (Hep/Col)2-coated samples and untreated samples. The EDX and FTIR results both confirmed the presence of heparin and collagen onto the modified samples. The immunofluorescence staining outcomes demonstrated that anti-CD34 antibody has successfully immobilized onto modified Mg discs.

Computational Modeling of the Mechanical Performance of a Magnesium Stent Undergoing Uniform and Pitting Corrosion in a Remodeling Artery

Coronary stents made from degradable biomaterials such as magnesium alloy are an emerging technology in the treatment of coronary artery disease. Biodegradable stents provide mechanical support to the artery during the initial scaffolding period after which the artery will have remodeled. The subsequent resorption of the stent biomaterial by the body has potential to reduce the risk associated with long-term placement of these devices, such as in-stent restenosis, late stent thrombosis, and fatigue fracture. Computational modeling such as finite-element analysis has proven to be an extremely useful tool in the continued design and development of these medical devices. What is lacking in computational modeling literature is the representation of the active response of the arterial tissue in the weeks and months following stent implantation, i.e., neointimal remodeling. The phenomenon of neointimal remodeling is particularly interesting and significant in the case of biodegradable stents, when both stent degradation and neointimal remodeling can occur simultaneously, presenting the possibility of a mechanical interaction and transfer of load between the degrading stent and the remodeling artery. In this paper, a computational modeling framework is developed that combines magnesium alloy degradation and neointimal remodeling, which is capable of simulating both uniform (best case) and localized pitting (realistic) stent corrosion in a remodeling artery. The framework is used to evaluate the effects of the neointima on the mechanics of the stent, when the stent is undergoing uniform or pitting corrosion, and to assess the effects of the neointimal formation rate relative to the overall stent degradation rate (for both uniform and pitting conditions).

A strain-mediated corrosion model for bioabsorbable metallic stents.

The need for corrosion models that explore the interaction of strain with corrosion damage has been recognised as one of the current challenges in degradable material modelling (Gastaldi et al., 2011). A finite element based plastic strain-mediated phenomenological corrosion model was developed in this work and was calibrated based on the results of the corrosion experiments. It was found to be capable of predicting the experimentally observed plastic strain-mediated mass loss profile and the corrosion-induced reduction in the radial stiffness of the stent over time. To the author's knowledge, the results presented here represent the first experimental calibration of a plastic strain-mediated corrosion model of a corroding magnesium stent.

Ex vivo blood vessel bioreactor for analysis of the biodegradation of magnesium stent models with and without vessel wall integration.

Magnesium and its alloys are candidates for a new generation of biodegradable stent materials. However, the in vitro degradation of magnesium stents does not match the clinical degradation rates, corrupting the validity of conventional degradation tests. Here we report an ex vivo vascular bioreactor, which allows simulation of the microenvironment with and without blood vessel integration to study the biodegradation of magnesium implants in comparison with standard in vitro test conditions and with in vivo implantations. The bioreactor did simulate the corrosion of an intramural implant very well, but showed too high degradation for non-covered implants. It is concluded that this system is in between static incubation and animal experiments concerning the predictivity of the degradation.

Plastic strains during stent deployment have a critical influence on the rate of corrosion in absorbable magnesium stents.

Magnesium stents are a promising candidate in the emerging field of absorbable metallic stents (AMSs). In this study, the mechanical and corrosion performance of dog-bone specimens and a specific stent design of a magnesium alloy, WE43, are assessed experimentally in terms of their corrosion behaviour and mechanical integrity. It is shown that plastic strains that are induced in the struts of the stent during stent deployment have a critical influence in directing subsequent corrosion behaviour within the material. In addition, the deployment and scaffolding characteristics of the magnesium stent are elucidated and contrasted with those of a commercial stainless steel stent. The magnesium stent is found to support higher levels of cyclic strain amplitude than the stainless steel stent, even prior to degradation, and this may play a role in reducing in-stent restenosis. This study provides new insights into the experimental performance of a current AMS design and material whilst demonstrating the critical influence of plastic strain on the corrosion performance and scaffolding ability of an AMS.

Silicone-covered biodegradable magnesium-stent insertion in the esophagus: a comparison with plastic stents.

Background:We determined the feasibility of, and tissue response to silicone-covered biodegradable magnesium- and plastic-stent insertion into the esophagus in rabbits.Methods:The mechanical compression–recovery characteristics and degradation behaviors of the magnesium stent were investigated in vitro. A total of 45 rabbits were randomly divided into a magnesium- (n = 15) and a plastic- (n = 15) stent group, and underwent stent insertion into the lower third of the esophagus under fluoroscopic guidance; a control group (n = 15) did not undergo the intervention. Esophagography was performed at 1, 2, and 4 weeks. Five rabbits in each group were euthanized at each time point for histological examination.Results:Silicone-covered magnesium stents showed similar radial force to plastic stents (p > 0.05). The magnesium stents degraded rapidly in an acidic solution, but 90.2% ± 3.1% of the residual mass was maintained after a 2-week degradation in a solution with a pH of 4.0. All stent insertions were well tolerated. Magnesium stents migrated in six rabbits (one at 1 week, one at 2 weeks and four at 4 weeks), and plastic stents migrated in three rabbits (one at 2 weeks and two at 4 weeks; p > 0.05). Esophageal wall remodeling (thinner epithelial and smooth muscle layers) was similar in both stented groups (p > 0.05), and the esophagus wall was found to be significantly thinner in the stented groups than in the control group (p < 0.05). Esophageal injury and collagen deposition following stent insertion were similar and did not differ from the control group (p > 0.05).Conclusions:Esophageal silicone-covered magnesium stents provided reliable support for at least 2 weeks, with acceptable migration rates and without causing severe injury or tissue reaction compared with plastic stents.

Technical feasibility and tissue reaction after silicone-covered biodegradable magnesium stent insertion in the oesophagus: a primary study in vitro and in vivo.

Determine the feasibility of and tissue response to biodegradable magnesium-silicone stent insertion into the oesophagus of rabbits. Mechanical compression-recovery and degradation behaviours of the stents were investigated in vitro. Thirty rabbits were randomly divided into a magnesium-silicone stent group (n = 15) that received stent insertion into the lower 1/3 of the oesophagus under fluoroscopic guidance and a control group (n = 15). Oesophagography was performed at 1, 2 and 4weeks. Five rabbits in each group were euthanized at each time point for histological examination. Magnesium-silicone stents showed good flexibility and elasticity, and degraded more slowly than bare stents at pH4.0 and 7.4. All stent insertions were well tolerated. The oesophageal diameters at 1, 2 and 4weeks were 9.7 ± 0.7, 9.6 ± 0.8 and 9.6 ± 0.5mm, respectively (vs. 9.2 ± 0.8mm before intervention; P > 0.05). Stent migration occurred in six rabbits (one at 1week, one at 2 and four at 4). Microscopy demonstrated dilation of the oesophageal wall within 1week of insertion. Oesophageal injury and collagen deposition following stent insertion were similar to control (P > 0.05). Oesophageal magnesium-silicone stent insertion was feasible and provided reliable support for 2weeks without causing oesophageal injury or collagen deposition. • Mg stent provided apparently adequate radial force and silicone membrane reduced magnesium biodegradation • Stent insertion provided good support for at least 2weeks before biodegradation • Stenting effectively resulted in oesophageal wall remodelling, without demonstrable injury.

Fabrication of a Delaying Biodegradable Magnesium Alloy-Based Esophageal Stent via Coating Elastic Polymer.

Esophageal stent implantation can relieve esophageal stenosis and obstructions in benign esophageal strictures, and magnesium alloy stents are a good candidate because of biodegradation and biological safety. However, biodegradable esophageal stents show a poor corrosion resistance and a quick loss of mechanical support in vivo. In this study, we chose the elastic and biodegradable mixed polymer of Poly(ε-caprolactone) (PCL) and poly(trimethylene carbonate) (PTMC) as the coated membrane on magnesium alloy stents for fabricating a fully biodegradable esophageal stent, which showed an ability to delay the degradation time and maintain mechanical performance in the long term. After 48 repeated compressions, the mechanical testing demonstrated that the PCL-PTMC-coated magnesium stents possess good flexibility and elasticity, and could provide enough support against lesion compression when used in vivo. According to the in vitro degradation evaluation, the PCL-PTMC membrane coated on magnesium was a good material combination for biodegradable stents. During the in vivo evaluation, the proliferation of the smooth muscle cells showed no signs of cell toxicity. Histological examination revealed the inflammation scores at four weeks in the magnesium-(PCL-PTMC) stent group were similar to those in the control group (p > 0.05). The α-smooth muscle actin layer in the media was thinner in the magnesium-(PCL-PTMC) stent group than in the control group (p < 0.05). Both the epithelial and smooth muscle cell layers were significantly thinner in the magnesium-(PCL-PTMC) stent group than in the control group. The stent insertion was feasible and provided reliable support for at least four weeks, without causing severe injury or collagen deposition. Thus, this stent provides a new stent for the treatment of benign esophageal stricture and a novel research path in the development of temporary stents in other cases of benign stricture.

Magnesium stent scaffolds: DREAMS become reality

Magnesium stent scaffolds: DREAMS become reality

Deformation behaviour of self-expanding magnesium stents based on auxetic chiral lattices

Current stenting solutions commonly employ metal alloys and are permanent. This fact has the consequence of diverse long term risks for the patients, e.g. Restenosis, late-term stent Thrombosis, etc. One possible solution to attenuate these problems is the use of polymer or metallic based bioabsorbable stents that tend to be degraded by corrosion and completely eliminated after their scaffolding duties are fulfilled. Additionally, there is a need to find new ways of deploying these devices. A route to fulfill this goal, can be the design of stents that eliminate the necessity of balloon expansion and are able to self-expand by their own deformation mechanism, for example by possessing auxetic behavior. The objective of this study is the modeling of a stent that reveals auxetic behavior and is composed by a biodegradable material (AZ91D Magnesium alloy), to embrace both recent tendencies on stenting designs. It is shown that the defined stent modeling is able to expand when stretched (auxetic behavior) and reveals a deformation mechanism that may be interesting for further development. In conclusion, the combination of both biodegradable and auxetic characteristics shown in this study may be a future step in the evolution of these medical devices.

Pulsed Laser Cutting of Magnesium-Calcium for Biodegradable Stents

There is growing interests in the use of biodegradable magnesium implants for cardiovascular and pulmonary applications such as stents. Magnesium is a metal that has the ability to gradually dissolve and absorb into the human body after implantation. There is very little work discussing the relationship between process parameters and cut quality of magnesium stents by laser cutting. The objective of this research is to determine the effect of laser cutting conditions including peak laser power and cutting speed of a millisecond range pulsed laser on kerf geometry, surface topography, surface roughness, and microstructure. An assessment on the experimental work discussing laser cutting of magnesium alloys is also presented.

生体内分解性マグネシウムステントの創製と機械的性質

生体内分解性マグネシウムステントの創製と機械的性質

Magnesium stent scaffolds: DREAMS become reality

Why are bioresorbable scaffolds so exciting? Simply because they fulfil the task of scaffolding the artery wall during the healing period, and thereafter vanish. In other words, their lifetime is adjusted to the healing process, thus avoiding any risk of causing a new disease (eg, late thrombosis, in-stent restenosis, or neoatherosclerosis) as can happen with permanent stents. Permanent stents do a perfect scaffolding job, but remain in place when they are no longer necessary, leading to a foreign body reaction with complications.

Biphasic responses of human vascular smooth muscle cells to magnesium ion

Magnesium-based alloys are promising in biodegradable cardiovascular stent applications. The degradation products of magnesium stents may have significant impacts on the surrounding vascular cells. However, knowledge on the interactions between magnesium ion and vascular cells at the molecular and cellular levels is still largely missing. Vascular smooth muscle cell (SMC) plays an important role in the pathogenesis of restenosis and wound healing after stent implantation. This study evaluated the short-term effects of extracellular magnesium ion (Mg(2+)) on the cellular behaviors of SMCs. Cellular responses to Mg(2+) were biphasic and in a concentration-dependent manner. Low concentrations (10 mM) of Mg(2+) increased cell viability, cell proliferation rate, cell adhesion, cell spreading, cell migration rate, and actin expression. In contrast, higher concentrations (40-60 mM) of Mg(2+) had deleterious effects on cells. Gene expression analysis revealed that Mg(2+) altered the expressions of genes mostly related to cell adhesion, cell injury, angiogenesis, inflammation, coagulation, and cell growth. Finding from this study provides some valuable information on SMC responses toward magnesium ions at the cellular and molecular levels, and guidance for future controlled release of magnesium from the stent material.

Coronary Stent Materials and Coatings: A Technology and Performance Update.

This paper reviews the current state of the art for coronary stent materials and surface coatings, with an emphasis on new technologies that followed on from first-generation bare metal and drug-eluting stents. These developments have been driven mainly by the need to improve long term outcomes, including late stent thrombosis. Biodegradable drug-eluting coatings aim to address the long term effects of residual durable polymer after drug elution; the SYNERGY, BioMatrix, and Nobori stents are all promising devices in this category, with minimal polymer through the use of abluminal coatings. Textured stent surfaces have been used to attached drug directly, without polymer; the Yukon Choice and BioFreedom stents have some promising data in this category, while a hydroxyapatite textured surface has had less success. The use of drug-filled reservoirs looked promising initially but the NEVO device has experienced both technical and commercial set-backs. However this approach may eventually make it to market if trials with the Drug-Filled Stent prove to be successful. Non-pharmacological coatings such as silicon carbide, carbon, and titanium-nitride-oxide are also proving to have potential to provide better performance than BMS, without some of the longer term issues associated with DES. In terms of biological coatings, the Genous stent which promotes attachment of endothelial progenitor cells has made good progress while gene-eluting stents still have some practical challenges to overcome. Perhaps the most advancement has been in the field of biodegradable stents. The BVS PLLA device is now seeing increasing clinical use in many complex indications while magnesium stents continue to make steady advancements.

Blood compatibility of a ferulic acid (FA)-eluting PHBHHx system for biodegradable magnesium stent application.

Magnesium stent has shown potential application as a new biodegradable stent. However, the fast degradation of magnesium stent limited its clinic application. Recently, a biodegradable and drug-eluting coating system was designed to prevent magnesium from fast degradation by adding ferulic acid (FA) in poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) by a physical method. In vitro study has demonstrated that the FA-eluting system exhibited strong promotion to the endothelialization, which might be a choice for the stent application. In this paper, the hemolysis rate, the plasma recalcification time (PRT), the plasma prothrombin time (PT) and the kinetic clotting time of the FA-eluting films were investigated and the platelet adhesion was observed in order to assess the blood compatibility of the FA-eluting PHBHHx films in comparison with PHBHHx film. The results have shown that the addition of FA had no influence on the hemolysis, but prolonged PRT, PT and the clotting time and reduced the platelet adhesion and activation, displaying that the FA-eluting PHBHHx exhibited better blood compatibility than PHBHHx. In addition, the effect of alkali treatment on the blood compatibility of FA-eluting PHBHHx was also studied. It was indicated that alkali treatment had no effect on the hemolysis and the coagulation time, but enhanced slightly the platelet adhesion. All these demonstrated that FA-eluting PHBHHx film had good blood compatibility and might be a candidate surface coating for the biodegradable magnesium stent.

A ferulic acid (FA)-eluting system for biodegradable magnesium stent: Cells response of HUVECs.

A new drug-eluting system was designed for biodegradable magnesium stents, in which ferulic acid (FA) was used as drug due to its promotion function to endothelial cells and PHBHHx as drug delivery due to its biodegradability and biocompatibility. A 5 and 10% FA were added in PHBHHx to prepare FA containing PHBHHX films. The cell adhesion, spreading and proliferation on these films was investigated in order to assess cell response of HUVECs. It was also found that FA enhanced the adhesion, spreading and proliferation of HUVECs in a dose-dependent manner. Cell viability after H2 O2 injury and NO production of HUVECs were also studied. The results indicated that FA effectively inhibited H2 O2 -induced injury and promotes NO production. It was also shown that alkali treatment improved the cell adhesion, spreading and proliferation while the treatment reduces the FA release and in turn reduces the inhibition on H2 O2 -induced injury and NO production. However, alkali treatment itself had no influence on the H2 O2 induced injure and NO production. The tensile shear strength between the FA containing coating and Mg substrate was also tested. All results demonstrated that FA containing PHBHHx films exhibited strong promotion to the endothelialization and could be a choice for surface modification of magnesium stent.