Biodegradable Polymer Stents Research Articles

Five-year outcomes of patients with diabetes mellitus treated with a sirolimus-eluting or a biolimus-eluting stents with biodegradable polymer. From the SORT OUT VII trial.

Diabetes mellitus is associated with higher risk of target lesion failure (TLF) after percutaneous coronary intervention. We studied the 5-year outcome in patients with diabetes mellitus treated with biodegradable polymer stents. The SORT OUT VII was a randomised trial comparing the ultrathin sirolimus-eluting Orsiro stent (O-SES) and the biolimus-eluting Nobori stent (N-BES) in an all-comer setting. Patients (n = 2525) were randomised to receive O-SES (n = 1261, diabetes: n = 236) or N-BES (n = 1264, diabetes: n = 235). Endpoints were TLF (a composite of cardiac death, target-lesion myocardial infarction (MI), target lesion revascularization (TLR)), definite stent thrombosis and a patient related outcome (all-cause mortality, MI and revascularization) within 5years. Patients with diabetes mellitus had higher TLF (20.6% vs 11.0%, (Rate ratio (RR) 1.85 95% confidence interval (CI): (1.42-2.40) and patient related outcome (42.0% vs 31.0%, RR 1.43 95% CI: (1.19-1.71)) compared to patients without diabetes. Among patients with diabetes mellitus, TLF after 5 years did not differ between O-SES and N-BES (21.2% vs 20.0%), RR 1.05 95% CI: (0.70-1.58), p = 0.81). Cardiac death, MI, TLR, and definite stent thrombosis did not differ between the groups. In patients with diabetes mellitus, 5-year outcomes were similar among patients treated with biodegradable polymer O-SES or N-BES. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01879358.

Structural optimization of degradable polymer vascular stents based on surrogate models

The clinical performance of biodegradable polymer stents implanted in blood vessels is affected by uneven degradation. Stress distribution plays an important role in polymer degradation, and local stress concentration leads to the premature fracture of stents. Numerical simulations combined with in vitro experimental validation can accurately describe the degradation process and perform structural optimization. Compared with traditional design techniques, optimization based on surrogate models is more scientifically effective. Three stent structures were designed and optimized, with the effective working time during degradation as the optimization goal. The finite element method was employed to simulate the degradation process of the stent. Surrogate models were employed to establish the functional relationship between the design parameters and the degradation performance. The proposed function models accurately predicted the degradation performance of various stents. The optimized stent structures demonstrated improved degradation performance, with the kriging model showing a better optimization effect. This study provided a novel approach for optimizing the structural design of biodegradable polymer stents to enhance degradation performance.

A biodegradable polymer stent with high radial performance: Potential for treatment of portal vein stenosis

AbstractBiodegradable polymer stents have a wide application prospect in the treatment of vascular stenosis diseases. However, weak radial performance of polymer stents hinders the treatment of the diseases with high demand for radial supporting, such as portal vein stenosis. According to previous research, the constraint mode between monofilaments is a key factor that affects the radial performance of polymer braided stent. In this work, a series of Poly(l‐lactic acid) (PLLA) stents with the elastomer coating were prepared by ultrasonic spraying process to realize the constraints of monofilament cross points. The results are showed that the radial stiffness and peak force of the coated stent are significantly increased, up to 28 and 35 times higher than that of the bare stent. It is found that the cross points are constrained by the coating, which improves the constraining force between the monofilaments resulting in the increase of the radial force during the deformation process. More importantly, the mechanism of action between the radial force of the coated stent and the mechanical performance of elastic coating has been proposed, revealing a significant positive correlation between them. The radial force of the coated stent could be quantitatively regulated by the six‐arm poly(l‐lactide‐co‐ε‐caprolactone) (6SPLCL) coating cross‐linked by Hexamethylene diisocyanate (HDI) in different proportions. Finally, we build a mechanical model of stents and find that there is a consistency between the theoretical curve and the actual curve trend. This provides further research and expands the application scope for improving the radial supporting performance of the biodegradable polymer stent.

Weekly journal scan: do biodegradable polymer stents provide a durable benefit in patients with ST-segment elevation myocardial infarction?

Weekly journal scan: do biodegradable polymer stents provide a durable benefit in patients with ST-segment elevation myocardial infarction?

Mechanical analysis of radial performance in biodegradable polymeric vascular stents manufactured using micro-injection molding

Micro-injection molding (MiM) is a promising technique for manufacturing biodegradable polymeric vascular stents (BPVSs) at scale, in which a trapezoidal strut cross section is needed to ensure high-quality de-molding. However, there is a lack of research on the influence of the strut cross-sectional shape on its mechanical properties, posing a challenge in determining the key geometries of the strut when using MiM to produce BPVSs. Hence, this work has investigated the relationships between the geometry parameters, including the de-molding angle, and the radial support property of BPVSs using the finite element method. The results reveal that the radial stiffness of BPVSs is significantly affected by the de-molding angle, which can be counteracted by adjusting strut height, bending radius, and strut thickness. Stress distribution analysis underscores the crucial role of the curved portion of the support ring during compression, with the inner side of the curved region experiencing stress concentration. A mathematical model has been established to describe the relationships between the geometry parameters and the radial support property of the BPVSs. Notably, the radius of the neutral layer emerges as a key determinant of radial stiffness. This study is expected to serve as a guideline for the development of BPVSs that can be manufactured using MiM.

Biodegradable Polymeric Stent: Poly(lactic acid) Variation

Stenting is a treatment procedure to insert an implant-like needle into the blood vessel for the purpose of removing plaque and thrombosis while supporting the weak blood vessel. This procedure will enlarge the narrow blood vessel and restore blood circulation. Specifically, stent implantation is being combined with coronary angioplasty procedure to be known as percutaneous coronary intervention (PCI), which is an approach to treat cardiovascular diseases (CVD). There are three main variations of commercialized stents: Bare metal stent, drug-eluting stent and biodegradable stent. These three variations are focusing on the utilization of metal as the base material. Biodegradable metallic stent is a metallic stent which can be degraded into the physiological environment following an implantation. Even though forthcoming complications of permanent stent can be overcome with this type of stent, the degradation products often trigger inflammation and disturb the cascaded physiological processes. Therefore, researchers are moving towards biodegradable polymeric stents that are able to degrade while not harming the implanted lesion and surrounding tissues. This review article is intended to expose the information on biodegradable polymeric stent specifically to the implementation of poly(lactic acid) (PLA) and its variation as the polymeric materials.

Focus on the crucial deformation region to adjust the comprehensive performance of poly (L-lactic acid) stent

The fully biodegradable polymer stent is considered as the fourth-generation vascular implant with good biocompatibility and long-term therapeutic potential. It has attracted much attention because it overcomes the disadvantage of the permanently implanted metal stent. However, compared with the metal stent, its mechanical properties are slightly inferior, which is an urgent problem. Based on previous studies, fully biodegradable polymer stents are prone to experience cracks and damage in large deformation region during the crimping and expansion process. The large deformation region is mainly located at the ring bend of the stent. We supposed that these damages are the leading causes of weakening the mechanical performance of polymer stents and are mainly affected by the crucial deformation region. For this purpose, this work studies the relationship between different crucial deformation regions and the mechanical performance of the polymer stent. Firstly, the volume of the crucial deformation region is improved by increasing the ring width. Although the radial strength of the stent is enhanced with the increase in ring width, the radial stiffness also increases, and correspondingly, the flexibility of the stent decreases. To obtain acceptable comprehensive mechanical performance, two types of slotting design in critical deformation region were proposed. The proposed slotted stent with a bulge has sufficient radial strength and low radial stiffness, having a good radial support capacity and flexibility. In other words, the proposed stent has improved the radial support without sacrificing flexibility. Overall, different crucial deformation regions cause different degrees of damage to the stent during crimping and expansion, which affects the mechanical properties of the stent. Reasonable structural design of the crucial deformation region is the key to adjust the comprehensive performance of the stent.

Development of Biodegradable Polymeric Stents for the Treatment of Cardiovascular Diseases.

Cardiovascular disease has become the leading cause of death. A vascular stent is an effective means for the treatment of cardiovascular diseases. In recent years, biodegradable polymeric vascular stents have been widely investigated by researchers because of its degradability and clinical application potential for cardiovascular disease treatment. Compared to non-biodegradable stents, these stents are designed to degrade after vascular healing, leaving regenerated healthy arteries. This article reviews and summarizes the recent advanced methods for fabricating biodegradable polymeric stents, including injection molding, weaving, 3D printing, and laser cutting. Besides, the functional modification of biodegradable polymeric stents is also introduced, including visualization, anti-thrombus, endothelialization, and anti-inflammation. In the end, the challenges and future perspectives of biodegradable polymeric stents were discussed.

Development of Organic/Inorganic Hybrid Materials for Fully Degradable Reactive Oxygen Species-Releasing Stents for Antirestenosis.

Despite innovative advances in stent technology, restenosis remains a crucial issue for the clinical implantation of stents. Reactive oxygen species (ROS) are known to potentially accelerate re-endothelialization and lower the risk of restenosis by selectively controlling endothelial cells and smooth muscle cells. Recently, several studies have been conducted to develop biodegradable polymeric stents. As biodegradable polymers are not electrically conductive, double metallic layers are required to constitute a galvanic couple for ROS generation. Here, we report a new biodegradable hybrid material composed of a biodegradable polymer substrate and double anodic/cathodic metallic layers for enhancing re-endothelialization and suppressing restenosis. Pure Zn and Mg films (3 μm thick) were deposited onto poly-l-lactic acid (PLLA) substrates by DC magnetron sputtering, and a long-term immersion test using biodegradable hybrid materials was performed in phosphate-buffered solution (PBS) for 2 weeks. The concentrations of superoxide anions and hydrogen peroxide generated by the corrosion of biodegradable metallic films were monitored every 1 or 2 days. Both superoxide anions and hydrogen peroxide were seamlessly generated even after the complete consumption of the anodic Mg layer. It was confirmed that the superoxide anions and hydrogen peroxide were formed not only by the galvanic corrosion between the anode and cathode layers but also by the corrosion of a single Mg or Zn layer. The corrosion products of the Mg and Zn films in PBS were phosphate, oxide, or chloride of the biodegradable metals. Thus, it is concluded that ROS generation by the corrosion of PLLA-based hybrid materials can be sustained until the exhaustion of the cathode metal layer.

A-11 | Short Term Outcomes Comparing Biodegradable Drug Eluting Stents Versus Durable Polymer Stents in Coronary Artery Disease - A Systematic Review and Meta Analysis

With advancement in the field of interventional cardiology, drug eluting stents (DES) with biodegradable polymer (BD) were developed in comparison to durable polymers (DP) to improve clinical outcomes in coronary artery disease. However, Results reported by multiple randomized controlled trials (RCTs) remain controversial.

Enhanced mechanical properties of poly(L‐lactide) braided stent with six‐arm poly(L‐lactide‐co‐ε‐caprolactone) coating cross‐linked by hexamethylene diisocyanate

AbstractCompared with traditional metal stents, biodegradable polymer stents have better biocompatibility but poorer mechanical properties in the treatment of vascular stenosis. It is necessary to improve the mechanical properties of biodegradable polymer stents for further application. For this purpose, we prepared a poly(L‐lactide) braided stent covered with six‐arm poly(L‐lactide‐co‐ε‐caprolactone) (6S‐PLCL) coating cross‐linked by hexamethylene diisocyanate (HDI) in different proportions. The coating causes an effective constraint on the movement of the monofilaments in the axial direction at the intersection. Due to this constraint, the coating enhanced mechanical properties of the stent and effectively reduced the axial elongation after crimping. Furthermore, the coated stent with the mass ratio of 5:1 (6S‐PLCL:HDI) showed the highest chronic outward force and the lowest axial elongation compared to the other mass ratios. The results can provide suggestions for improving the mechanical properties of polymer‐braided stents as compared to traditional metal stents.

A setup to characterize the tensile mechanical properties of poly(L-lactic acid) materials applied in bioresorbable polymer stents

A method for testing mechanical properties of miniature poly(L-lactic acid)(PLLA) specimens is instrumented and set up in this research. This method is specially designed to measure mechanical properties, including elasticity modulus, yield strength and breaking elongation, of miniature PLLA specimens in three different shapes at various tensile speeds and temperatures. Moreover, the measurement results are significantly dependent on the tensile speeds and temperatures. This phenomenon further verifies the obvious existence of the viscoelasticity of PLLA. Finally, it can be concluded that, with this method, mechanical properties of PLLA can be better investigated and understood, especially for PLLA used for biodegradable polymer stents.

Polymer selection for Eustachian tube stent application based on mechanical, thermal and degradation behavior

Abstract The novel concept of stenting the Eustachian tube was established to provide an effective and safe therapy of Eustachian tube dysfunction. Biodegradable polymer stents are being developed to restore impaired tube function. As the supporting effect may be required for different time periods, PLA-co-PEG copolymers, PLLGA, PDLLA and PDS, having shorter degradation times compared to PLLA, were evaluated as potential stent materials. Since tensile tests and thermal analyses of solvent cast films from PLA-co-PEG copolymers showed comparable properties to PLLA, stent samples were manufactured from these materials. Mechanical stent testing revealed an increase of elastic recoil and slight decrease of collapse pressure compared to PLLA. In a short term accelerated degradation study a considerable percentage molar mass reduction and an increasing degree of crystallinity depending on PEG content was found. Based on the results obtained, the tested polymers offer a promising, faster degradable alternative to the established stent material PLLA.

Real-World Clinical Outcomes of Indigenous Biodegradable Polymer Drug-Eluting Stents.

IntroductionThe durable polymer has been shown to cause neoatherosclerosis, and chronic local inflammation, predisposing individuals to in-stent restenosis and stent thrombosis (ST). The biodegradable polymer stents, which degrade after the desired function of drug release is achieved, allow for endothelial healing. Indigenous coronary stent manufacturing and its use are on the rise nowadays, and their safety and efficacy have been studied in well-structured clinical trials. However, data are scarce on their safety and efficacy in the real-world clinical setting. In this study, we examine the real-world one-year performance of bioresorbable or polymer-free stents manufactured in India.Materials and methodsThis was a single-center, single-arm prospective observational study involving 210 patients undergoing intracoronary stenting using bioabsorbable or polymer-free drug-eluting stents (DES) from Indian manufacturers. All patients were followed up for 12 months prospectively for any major clinical events.ResultsThe mean age of the enrolled patients was 57.04 years (IQR: 34-84 years), among which 159 (75.7%) were male; 99 (43.8%) patients had presented with acute myocardial infarction (MI). A total of 294 stents were deployed with a mean diameter of 3.1 ±0.4 mm, and a mean length of 29.4 ±9.1 mm. Two patients had experienced major adverse cardiovascular events (MACE). After three months of follow-up, one patient developed ST, and the same patient developed a cerebrovascular accident (CVA) after six months. After one year of follow-up, one patient died of cardiac causes.ConclusionBased on our findings, in the real-world clinical setting, the indigenously made biodegradable polymer DES are both safe and effective.

Comparative Study Between Biodegradable-Polymer Stents and Standard Drug-Eluting Stents in Diabetic Patients Presenting With Acute Coronary Syndrome

Comparative Study Between Biodegradable-Polymer Stents and Standard Drug-Eluting Stents in Diabetic Patients Presenting With Acute Coronary Syndrome

Design and Shape Optimization of a Biodegradable Polymeric Stent for Curved Arteries Using FEM

Stent treatment has revealed safe and efficient outcomes for straight arteries, while it is still challenging for curved coronary arteries. On the one hand, a stent should be flexible enough to take the artery’s curvature with the least stress to the artery wall. On the other hand, it has to be strong enough to prevent any artery diameter reduction after the implant. In this work, the genetic algorithm multi-objective optimization method is exploited to provide a Pareto set and to design a curvature stent. The design has been performed based on the appropriate flexibility and radial strength design, depending on the characteristics of a particular case study. In the optimization procedure, flexibility and radial strength have been evaluated based on ASTM standard mechanical tests. These tests have been parametrically simulated using the finite element method. The strut curvature is formed by the spline curvature, whose middle point coordinates are two of the optimization variables. The other optimization variable is the thickness of the stent. Based on the Pareto set achieved from the optimization, five different stent designs have been proposed. In these designs, the middle part of the stent is stiffer (in the plaque aggregated) and benefits more radial strength rather than flexibility. At the stent’s extremes, where more deformation takes place, flexibility is weighted more than radial strength. These five design sets differ in their objective weight ratios. At the end of this research, their implementation in a curved vessel is simulated in ABAQUS/CAE, and von Mises stress distribution, maximum von Mises stress, and stent recoil after imposing the stent have been analyzed. The obtained Pareto front can also be a useful guide for physicians to design and manufacture customized stents for each patient.

Design and mechanical properties of biodegradable polymeric stent

Biodegradable stents (BDSs) are the milestone in percutaneous coronary intervention(PCI). Biodegradable polymeric stents have received widespread attention due to their good biocompatibility, moderate degradation rate and degradation products without toxicity or side effects. However, due to the defects in mechanical properties of polymer materials, the clinical application of polymeric BDS has been affected. In this paper, the BDS geometric configuration design was analyzed to improve the radial strength, flexibility and reduce the shrinkage rate of biodegradable polymeric stents. And from the aspects of numerical simulation, in vitro experiment and animal experiment, the configuration design and mechanical properties of biodegradable polymeric stents were introduced in detail in order to provide further references for the development of biodegradable polymeric stents.

BioMatrix versus Orsiro biodegradable polymer stents in all-comer patients with coronary artery disease: the multicentre, randomised BIODEGRADE trial.

The aim of this trial was to compare the safety and efficacy of a thin-strut biodegradable polymer sirolimus-eluting cobalt-chromium stent (Orsiro) to a thick-strut biodegradable polymer biolimus-eluting stent (BioMatrix). This randomised, open-label, non-inferiority trial was conducted among patients undergoing percutaneous coronary intervention. The primary endpoint was target lesion failure (TLF). Between July 2014 and September 2017, we randomly assigned 2,341 patients to BioMatrix stents (n=1,166) or Orsiro stents (n=1,175). We analysed 2,327 patients who completed 18-month follow-up. The mean patient age was 63.5 years, and 1,565 (67.3%) patients presented with acute coronary syndrome. At 18 months, 34 (2.9%) patients with BioMatrix stents and 24 (2.1%) with Orsiro stents experienced TLF (hazard ratio [HR] 0.70, upper limit of one-sided 95% confidence interval: 1.18, p for non-inferiority <0.0001). No significant differences were noted in rates of cardiac death (16 [1.4%] vs 12 [1.0%], p=0.558), target lesion-related myocardial infarction (0 [0%] vs 3 [0.3%], p=0.250), target lesion revascularisation (18 [1.6%] vs 10 [0.9%], p=0.124), or stent thrombosis (0 [0%] vs 2 [0.2%], p=0.50). In patients with a high prevalence of acute coronary syndrome, Orsiro stents were not inferior to BioMatrix stents. Both showed good clinical outcomes.

Polymeric stents for the Eustachian tube: development and human cadaver study

Abstract Impairment of Eustachian tube function with nonsufficient ventilation of the middle ear is a main cause for chronic otitis media. To provide an effective and safe therapy, the innovative concept of Eustachian tube stenting was established. Biodegradable polymeric stents are developed to restore impaired tube function and dissolve after fulfilling their supportive purpose. To evaluate the applicability of the stents in the Eustachian tube, prototypes in conjunction with corresponding implantation instruments were tested in human cadaver studies. Radiopaque markers and a diaphanoscopic approach were tested as additional features to prove correct positioning of catheter and stent in the tube. In the current study biodegradable polymeric stents were implanted in the Eustachian tube of human cadavers without difficulty. Correct positioning of the stents in the tube was proved by diaphanoscopy during intervention and postoperative tomographic and histological analyses. Once designs are optimized on the basis of cadaver studies, preclinical safety and efficacy studies using animal models will be initiated.

Flexibility of Biodegradable Polymer Stents with Different Strut Geometries.

Objective: Biodegradable stents (BDSs) represent a new technological development in the field of cardiovascular angioplasty; good flexibility helps stents pass through tortuous vessels during delivery and reduces the amount of damage caused to blood vessels. This study investigates the relationship between flexibility and the geometry of BDS struts. Methods: Four stent struts with different geometry (circular, triangular, hexagonal, and spline curved) and the same links were modeled to evaluate their flexibility via a three-point bending experimental method and a numerical method. Results: The bending state of the four stents was well-balanced. The bending effect of the four stents was different. Under the same conditions, the circular and spline curved stents showed the best bending effects while the hexagonal stent was the worst. However, these differences were not significant. Conclusion: The flexibility of BDSs is related to the geometry of the struts and links; however, the geometry of the struts has less effect on flexibility than the links. The greater the area enclosed by the strut centerline, the better flexibility of the stent.