The Current Literature on Bioabsorbable Stents: a Review.

PURPOSE OF REVIEW: The purpose of this review is to explore the evolution of the coronary stent, from the advent of bare-metal stents, to the newest adopted technology of bioresorbable vascular scaffolds (BVS) used in bioresorbable stents. To date, there have been conflicting data regarding the safety and efficacy of BVS stents, especially when compared to current-generation drug-eluting stents (DES). This review will cover the data that exist regarding current BVS stents, as well as the active clinical trials for future iterations of BVS. RECENT FINDINGS: The ABSORB BVS, the most widely circulated stent of its class, was promised to decrease rates of stent thrombosis and target vessel revascularization. Several randomized control trials, however, found the opposite to be true, with the ABSORB BVS demonstrating higher rates of thrombosis, target vessel revascularization, and even target lesion myocardial infarctions when compared to current-generation DES. These data caused the product to be pulled from all markets, leaving the field with uncertainty as to the role of BVS in coronary interventions. Coronary stents have evolved significantly from 1977, when they were first introduced. The original bare-metal stent was later fitted with a drug-eluting polymer, to prevent restenosis and thrombosis over time. Subsequent iterations of the stent attempted to further mitigate that risk by replacing the durable polymer to one that is bioresorbable. The final step in this progression was to create a stent that was fully bioresorbable, which Abbott did with the creation of their ABSORB BVS stent. The product, however, was found to perform poorly when compared to current-generation drug-eluting stents, with several trials showing high rates of stent thrombosis (ST), late stent thrombosis (LST), target-lesion myocardial infarction, and target vessel revascularization. Observational studies of BVS stents have proposed several mechanisms for their thrombogenicity, including higher stent-strut profiles leading to turbulent flow, low radial strength leading to strut disruption, and a higher propensity for neoatherosclerosis. Given the failure of the first-generation BVS stent, but the lingering desire for fully bioresorbable scaffolds, various manufacturers have proposed their solutions with new stents. Until data from their clinical trials emerge, it remains unclear whether fully bioresorbable stents will play any role in coronary interventions.

A review: Percutaneous pulmonary artery stenosis therapy: state-of-the-art and look to the future.

Stenosis, or narrowing, of the branches of the pulmonary artery is a type of CHD that, if left untreated, may lead to significant complications. Ideally, interventions to treat stenosis occur before significant complications or long-term sequelae take place, often within the first 2 years of life. Treatment depends on specifics of the condition, the presence of other malformations, and age of the child. Research and recent innovation to address these shortcomings have provided physicians with safer and more effective methods of treatment. This has further continued to push the ceiling of pulmonary arterial stenosis treatment available for patients. Despite continuous advancement in angioplasty - such as conventional and cutting balloon - and stenting, each treatment method is not without its unique limitations. New technological developments such as bioresorbable stents can accommodate patient growth and pulmonary artery stenosis treatment. As more than a decade has passed since the review by Bergersen and Lock, this article aims to provide a contemporary summary and investigation into the effectiveness of various therapeutic tools currently available, such as bare metal stents and potential innovations including bioresorbable stents.

Identifying Gaps in Technology for Congenital Interventions: Analysis of a Needs Survey from Congenital Interventional Cardiologists.

We carried out a device-needs survey to evaluate the gaps in device and equipment availability for congenital interventional cardiologists. As the complexity and demand for more complete solutions to congenital heart lesions increase, there is a growing need for modification and development of devices and equipment to support this endeavor. The survey was sent out via e-mail to members of the Congenital Cardiovascular Interventional Study Consortium and the Society for Cardiac Angiography and Interventions with a reach of over 350 congenital interventionalists. Responses were received from 68 cardiologists in 8 countries. In terms of the most desired device, 41 % ranked bioresorbable stents as their first choice from a list of 12 possible devices. Similarly, 23 % ranked large covered stents as their first choice. Twenty-seven percent of participants believed bioresorbable stents would have the greatest potential to improve morbidity of their patients, with another 27 % reporting that covered stents would have the greatest impact. Fifty percent of participants reported that they would like to see large covered stents available in their country. These data point toward a perceived need for the development/approval of bioresorbable stents for the pediatric age group, as well as the need to approve the use of large covered stents in the pediatric age group in the USA.

Dexamethasone eluting polydopaminated polycaprolactone-poly (lactic-co-glycolic) acid for treatment of tracheal stenosis.

Tracheal stenosis is commonly caused by injury, resulting in inflammation and fibrosis. Inhibiting inflammation and promoting epithelization can reduce recurrence after initial successful treatment of tracheal stenosis. Steroids play an important role in tracheal stenosis management. This study in vitro evaluated effectiveness of a polydopaminated polycaprolactone stent coated with dexamethasone-eluting poly(lactic-co-glycolic) acid microparticles (µPLGA) for tracheal stenosis management. Polydopamination was characterized by Raman spectroscopy and promoted epithelialization while dexamethasone delivery reduced macrophage activity, assessed by individual cell area measurements and immunofluorescent staining for inducible nitric oxide synthase (iNOS). Dexamethasone release was quantified by high-performance liquid chromatography over 30 days. Activation-related increase in cell area and iNOS production by RAW 264.7 were both reduced significantly (p < .05) through dexamethasone release. Epithelial cell spreading was higher on polydopaminated polycaprolactone (PCL) than PCL-alone (p < .05). Force required for stent migration was measured by pullout tests of PCL-µPLGA stents from cadaveric rabbit and porcine tracheas (0.425 ± 0.068 N and 1.082 ± 0.064 N, respectively) were above forces estimated to occur during forced respiration. Biomechanical support provided by stents to prevent airway collapse was assessed by comparing compressive circumferential stiffness, and stiffness of the stent was about 1/10th of the rabbit trachea (0.156 ± 0.023 N/mm vs. 1.420 ± 0.194 N/mm, respectively). A dexamethasone-loaded PCL-µPLGA stent platform can deliver dexamethasone and exhibits sufficient mechanical properties to anchor within the trachea and polydopamination of PCL is conducive to epithelial layer formation. Therefore, a polydopaminated PCL-µPLGA stent is a promising candidate for in vivo evaluation for treatment of tracheal restenosis.

Five-Year Outcomes of Bioresorbable Stent Therapy for Coronary Heart Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.

Temporal changes in coronary plaque as assessed by an artificial intelligence-based optical coherence tomography: from the first-in-human trial on DREAMS 3G scaffold.

AIMS: The aim of the study is to assess the impact of the baseline plaque composition on the DREAMS 3G luminal late loss and to compare the serial plaque changes between baseline and 6 and 12 months (M) follow-up. METHODS AND RESULTS: A total of 116 patients were enrolled in the BIOMAG-I trial. Patients were imaged with optical coherence tomography (OCT) pre- and post-DREAMS 3G implantation and at 6 and 12 M. OCTPlus software uses artificial intelligence to assess composition (i.e. lipid, calcium, and fibrous tissue) of the plaque. The differences between the OCT-derived minimum lumen area (MLA) post-percutaneous coronary intervention and 12 M were grouped into three terciles. Patients with larger MLA differences at 12 M (P = 0.0003) had significantly larger content of fibrous tissue at baseline. There was a reduction of 24.8% and 20.9% in lipid area, both P < 0.001, between the pre-DREAMS 3G OCT and the 6 and 12 M follow-up. Conversely, the fibrous tissue increased by 48.4% and 36.0% at 6 and 12 M follow-up, both P < 0.001. CONCLUSION: The larger the fibrous tissue in the lesion at baseline, the larger the luminal loss seen at 6 and 12 M. Following the implantation of DREAMS 3G, favourable healing of the vessel coronary wall occurs as shown by a decrease in the lipid area and an increase in fibrous tissue.

An Innovative Stereolithography 3D Tubular Method for Ultrathin Polymeric Stent Manufacture: The Effect of Process Parameters.

In the last decades, researchers have been developing bioresorbable stents (BRS) to overcome the long-term complications of drug-eluting stents (DES). However, BRS technology still presents challenging limitations in terms of manufacturing, materials, or mechanical properties. At this juncture, companies have developed ultrathin DES that may further improve the efficacy and safety profile of traditional DES by reducing the risk of target-lesion and target-vessel failures until BRS are developed. Nonetheless, the metallic platform of ultrathin DES still presents problems related to their cellular response. The use of polymers as a permanent platform in DES has not previously been studied due to the limitations of current manufacturing technologies. In this work, an innovative manufacturing method for polymeric stent production using tubular stereolithography (SLA) technology is proposed both for BRS and for ultrathin polymeric DES. The effects of manufacturing process parameters were studied by modelling the outcomes (stent thickness and strut width) with the key manufacturing variables (exposure, resin volume, and number of layers). Two different laser setups were used to compare the results. Microscopy results proved the merit of this novel tubular SLA process, which was able to obtain stents with 70 µm strut width and thickness in barely 4 min using only 0.2 mL of resin. Differential Scanning Calorimetry (DSC) results showed the stability of the manufacturing method. The results obtained with this innovative technology are promising and overcome the limitations of other previously used and available technologies.

Zn-Mg-WC Nanocomposites for Bioresorbable Cardiovascular Stents: Microstructure, Mechanical Properties, Fatigue, Shelf Life, and Corrosion.

Zinc (Zn) and Zn alloys have been studied as potential materials for bioresorbable stents (BRSs) in the last decade due to their favorable biodegradability and biocompatibility. However, most Zn alloys lack the necessary combination of strength, ductility, fatigue resistance, corrosion rate (CR), and thermal stability needed for such applications. In this study, nanoparticles made of tungsten carbide (WC) were successfully incorporated into Zn alloyed with 0.5 wt % magnesium (Mg) and evaluated for their suitability for BRS applications. Specifically, the resulting Zn-0.5Mg-WC nanocomposite's microstructure, mechanical properties, in vitro CR, and thermal stability were evaluated. The Zn-0.5Mg-WC nanocomposite had excellent mechanical strength [ultimate tensile strength (UTS) > 250 MPa], elongation to failure (>30%), and a suitable in vitro CR (∼0.02 mm/y) for this clinical application. Moreover, the Zn-0.5Mg-WC nanocomposite survived 10 million cycles of tensile loading (stress ratio, R = 0.053) when the maximum stress was 80% of the yield stress. Its ductility was also retained during a 90-day thermal stability study, indicating an excellent shelf life. Stent prototypes were fabricated using this composition and were successfully deployed during bench testing without fracture. These results show that the Zn-0.5Mg-WC nanocomposite is a promising material for BRS applications. In vivo studies are underway to validate both biocompatibility, stent function, and degradation.

3D-printed Bioresorbable Stent Coated with Dipyridamole-Loaded Nanofiber for Restenosis Prevention and Endothelialization.

Intimal hyperplasia and restenosis caused by excessive proliferation of smooth muscle cells (SMC) are the main factors for the failure of stent implantation. Drug-eluting stents carried with antiproliferative drugs have emerged as a successful approach to alleviate early neointimal development. However, these agents have been reported to have an undesirable effect on re-endothelialization. In this study, we proposed an integrated bioresorbable stent coated with dipyridamole (DP)-loaded poly(D,L-lactide) (PDLLA) nanofibers. Three-dimensional (3D) bioresorbable stents were fabricated by printing on a rotation mandrel using polycaprolactone (PCL), and the stents were further coated with PDLLA/DP nanofibers. The in vitro degradation and drug release evaluation illustrated the potential for long-term release of DP. Stents coated with PDLLA/DP nanofibers showed excellent hemocompatibility. The cell viability, proliferation, and morphology analysis results revealed that stents coated with PDLLA/DP nanofibers could prevent the proliferation of SMC and have no adverse effects on endothelial cells. The in vivo implantation of stents coated with PDLLA/DP nanofibers showed initial patency and continuous endothelialization and alleviated neointimal formation. The attractive in vitro and in vivo performance indicated its potential for restenosis prevention and endothelialization.

An experimental investigation into the physical, thermal and mechanical degradation of a polymeric bioresorbable scaffold.

This study presents a comprehensive evaluation of the mechanical, micro-mechanical and physical properties of Reva Medical Fantom Encore Bioresorbable Scaffolds (BRS) subjected to a thermally-accelerated degradation protocol. The Fantom Encore BRS were immersed in phosphate buffered saline solution at 50 °C for 112 days with radial compression testing, nanoindentation, differential scanning calorimetry, gel permeation chromatography and mass loss characterisation performed at consecutive time points. In the initial stages of degradation (Days 0-21), the Fantom Encore BRS showed increases in radial strength and stiffness, despite a substantial reduction in in molecular weight, with a slight increase in the melt temperature also observed. In the second phase (Days 35-54), the radial strength of the BRS samples were maintained despite a continued loss in molecular weight. However, during this phase, the ductility of the stent showed a reduction, with stent fracture occurring earlier in the crimp process and with lower amounts of plastic deformation evident under visual examination post-fracture. In the final phase (Days 63-112), the load-bearing capacity of the Fantom Encore BRS showed continued reduction, with decreases in radial stiffness and strength, and drastic reduction in the work-to-fracture of the devices. Throughout each phase, there was a steady increase in the relative crystallinity, with limited mass loss until day 112 and only minor changes in glass transition and melt temperatures. Limited changes were observed in nano-mechanical properties, with measured local elastic moduli and hardness values remaining largely similar throughout degradation. Given that the thermally-accelerated in vitro conditions represented a four-fold acceleration of physiological conditions, these results suggest that the BRS scaffolds could exhibit substantially brittle behaviour after âˆ¼ one year of implantation.

Effect of Parylene C on the Corrosion Resistance of Bioresorbable Cardiovascular Stents Made of Magnesium Alloy 'Original ZM10'.

Magnesium (Mg) alloy has attracted significant attention as a bioresorbable scaffold for use as a next-generation stent because of its mechanical properties and biocompatibility. However, Mg alloy quickly degrades in the physiological environment. In this study, we investigated whether applying a parylene C coating can improve the corrosion resistance of a Mg alloy stent, which is made of 'Original ZM10', free of aluminum and rare earth elements. The coating exhibited a smooth surface with no large cracks, even after balloon expansion of the stent, and improved the corrosion resistance of the stent in cell culture medium. In particular, the parylene C coating of a hydrofluoric acid-treated Mg alloy stent led to excellent corrosion resistance. In addition, the parylene C coating did not affect a polymer layer consisting of poly(ε-caprolactone) and poly(D,L-lactic acid) applied as an additional coating for the drug release to suppress restenosis. Parylene C is a promising surface coating for bioresorbable Mg alloy stents for clinical applications.

Advances in the development of biodegradable coronary stents: A translational perspective.

Implantation of cardiovascular stents is an important therapeutic method to treat coronary artery diseases. Bare-metal and drug-eluting stents show promising clinical outcomes, however, their permanent presence may create complications. In recent years, numerous preclinical and clinical trials have evaluated the properties of bioresorbable stents, including polymer and magnesium-based stents. Three-dimensional (3D) printed-shape-memory polymeric materials enable the self-deployment of stents and provide a novel approach for individualized treatment. Novel bioresorbable metallic stents such as iron- and zinc-based stents have also been investigated and refined. However, the development of novel bioresorbable stents accompanied by clinical translation remains time-consuming and challenging. This review comprehensively summarizes the development of bioresorbable stents based on their preclinical/clinical trials and highlights translational research as well as novel technologies for stents (e.g., bioresorbable electronic stents integrated with biosensors). These findings are expected to inspire the design of novel stents and optimization approaches to improve the efficacy of treatments for cardiovascular diseases.

Recent advances and directions in the development of bioresorbable metallic cardiovascular stents: Insights from recent human and in vivo studies.

Over the past two decades, significant advancements have been made regarding the material formulation, iterative design, and clinical translation of metallic bioresorbable stents. Currently, magnesium-based (Mg) stent devices have remained at the forefront of bioresorbable stent material development and use. Despite substantial advances, the process of developing novel absorbable stents and their clinical translation is time-consuming, expensive, and challenging. These challenges, coupled with the continuous refinement of alternative bioresorbable metallic bulk materials such as iron (Fe) and zinc (Zn), have intensified the search for an ideal absorbable metallic stent material. Here, we discuss the most recent pre-clinical and clinical evidence for the efficacy of bioresorbable metallic stents and material candidates. From this perspective, strategies to improve the clinical performance of bioresorbable metallic stents are considered and critically discussed, spanning material alloy development, surface manipulations, material processing techniques, and preclinical/biological testing considerations. STATEMENT OF SIGNIFICANCE: Recent efforts in using Mg, Fe, and Zn based materials for bioresorbable stents include elemental profile changes as well as surface modifications to improve each of the three classes of materials.  Although a variety of alloys for absorbable metallic stents have been developed, the ideal absorbable stent material has not yet been discovered. This review focuses on the state of the art for bioresorbable metallic stent development. It covers the three bulk materials used for degradable stents (Mg, Fe, and Zn), and discusses their advances from a translational perspective. Strategies to improve the clinical performance of bioresorbable metallic stents are considered and critically discussed, spanning material alloy development, surface manipulations, material processing techniques, and preclinical/biological testing considerations.

The Development of Design and Manufacture Techniques for Bioresorbable Coronary Artery Stents.

Coronary artery disease (CAD) is the leading killer of humans worldwide. Bioresorbable polymeric stents have attracted a great deal of interest because they can treat CAD without producing long-term complications. Bioresorbable polymeric stents (BMSs) have undergone a sustainable revolution in terms of material processing, mechanical performance, biodegradability and manufacture techniques. Biodegradable polymers and copolymers have been widely studied as potential material candidates for bioresorbable stents. It is a great challenge to find a reasonable balance between the mechanical properties and degradation behavior of bioresorbable polymeric stents. Surface modification and drug-coating methods are generally used to improve biocompatibility and drug loading performance, which are decisive factors for the safety and efficacy of bioresorbable stents. Traditional stent manufacture techniques include etching, micro-electro discharge machining, electroforming, die-casting and laser cutting. The rapid development of 3D printing has brought continuous innovation and the wide application of biodegradable materials, which provides a novel technique for the additive manufacture of bioresorbable stents. This review aims to describe the problems regarding and the achievements of biodegradable stents from their birth to the present and discuss potential difficulties and challenges in the future.

Investigation on large elastoplastic deformation in expansion and springback for a composited bioresorbable stent.

Mechanical performances for a composited bioresorbable stent were investigated by using the finite element method, which concerns the elastoplastic large deformation of expansion and springback during stent implantation. The introduced stent is composited by the outer layer of poly-L-lactic acid (PLLA) and the core of magnesium alloy (Mg alloy). As comparisons, meanwhile two single-material stents of PLLA and Mg alloy with the same geometric structures as the composited stent were considered. The numeric simulation results indicated that, the wrapping of PLLA can make the maximum Mises stress locate at the interior, it is beneficial to slow down the earlier surface degradation of stents caused by stress concentration. Also, the variation of residual deformation and stress distribution in Mg alloy core after PLLA outer layer degraded entirely are analyzed. The distributions of normal and total shear stresses on the interface of two materials were also calculated for the cases of expansion and springback. In addition, the analysis reveals the radius of implanted stent is in approximate linearly related to the expansion displacement load.

In vitro and in silico testing of partially and fully bioresorbable vascular scaffold.

Coronary artery disease (CAD), one of the leading causes of death globally, occurs due to the growth of atherosclerotic plaques in the coronary arteries, causing lesions which restrict the flow of blood to the myocardium. Percutaneous transluminal coronary angioplasty (PTCA), including balloon angioplasty and coronary stent deployment is a standard clinical invasive treatment for CAD. Coronary stents are delivered using a balloon catheter inserted across the lesion. The balloon is inflated to a nominal pressure, opening the occluded artery, deploying the stent and improving the flow of blood to the myocardium. All stent manufacturers have to perform standard in vitro mechanical testing under different physiological conditions. In this study, partially and fully bioresorbable vascular scaffolds (BVS) from Boston Scientific Limited have been examined in vitro and in silico for three different test methods: inflation, radial compression and crush resistance. We formulated a material model for poly-L-lactic acid (PLLA) and implemented it into our in-house software tool. A comparison of the different experimental results is presented in the form of graphs showing displacement-force curves, diameter - load curves or diameter - pressure curves. There is a strong correlation between simulation and real experiments with a coefficient of determination (R2) > 0.99 and a correlation coefficient (R) > 0.99. This preliminary study has shown that in-silico tests can mimic the applicable ISO standards for mechanical in vitro stent testing, providing the opportunity to use data generated using in-silico testing to partially or fully replacing the mechanical testing required for regulatory submission.

Physical and mechanical degradation behaviour of semi-crystalline PLLA for bioresorbable stent applications.

This study presents a systematic evaluation of the physical, thermal and mechanical performance of medical-grade semi-crystalline PLLA undergoing thermally-accelerated degradation. Samples were immersed in phosphate-buffered saline solution at 50 °C for 112 days and mass loss, molecular weight, thermal properties, degree of crystallinity, FTIR and Raman spectra, tensile elastic modulus, yield stress and failure stress/strain were evaluated at consecutive time points. Samples showed a consistent reduction in molecular weight and melting temperature, a consistent increase in percent crystallinity and limited changes in glass transition temperature and mass loss. At day 49, a drastic reduction in tensile failure strain was observed, despite the fact that elastic modulus, yield and tensile strength of samples were maintained. Brittleness increase was followed by rapid increase in degradation rate. Beyond day 70, samples became too brittle to test indicating substantial deterioration of their load-bearing capacity. This study also presents a computational micromechanics framework that demonstrates that the elastic modulus of a semi-crystalline polymer undergoing degradation can be maintained, despite a reducing molecular weight through compensatory increases in percent crystallinity. This study presents novel insight into the relationship between physical properties and mechanical performance of medical-grade PLLA during degradation and could have important implications for design and development of bioresorbable stents for vascular applications.

First-in-Man trial of a drug-free bioresorbable stent designed to minimize the duration of coronary artery scaffolding.

For the last two decades, various degradable stents have been proposed to treat coronary artery diseases and replace metallic stents to avoid residual foreign material after healing. To date, the right balance between suitable scaffolding and loss of radial strength soon after endothelium restoration is still an unmet need. The present article reports on the First-in-Man trial of a drug-free bioresorbable stent based on a lactic acid stereocopolymer composed of 98% l-lactyl units selected to release stress shielding earlier than in the case of homopoly(l-lactic acid). Thirty patients with single de novo coronary lesions were included in the trial. The fate of scaffolds was monitored by clinical and imaging follow-ups to assess rate of adverse events, acute recoil, late luminal loss, and late lumen recovery. There was no death, no myocardial infarction, and no stent thrombosis observed over the 36 months trial. Dismantling occurred about 3 months after implantation. Bioresorption was almost completed at 2 years. The late lumen loss observed at the end of the first year was partly compensated one year later by enlarging remodeling. At one year, a neointimal hyperplasia slightly greater than for drug-eluting metallic and bioresorbable stents was shown using optical coherence tomography. The excess of hyperplasia was discussed relative to struts thickness, absence of anti-proliferative drug, and release of degradation by-products.