Bioresorbable Vascular Stents Research Articles

3D-printed bioresorbable vascular stents: emerging frontiers in personalized cardiac care

3D-printed bioresorbable vascular stents: emerging frontiers in personalized cardiac care

A phenomenological model of pulsatile blood pressure-affected degradation of polylactic acid (PLA) vascular stent.

The stent implantation may alter the post-operative patient's blood pressure, and bioresorbable vascular stents (BVS) as a candidate to treat vascular diseases, its degradation is affected by mechanical stress, thus, the altered pressure representing varying stress level will result in different degradation behaviors of the BVS. This paper first proposed a novel stress-regulated PLA degradation model that included swelling factor, and then the degradation evolutions of a PLA BVS within 180days under normal and high blood pressures were simulated by finite element method, and more four degradation indexes were defined to study the effects of the two blood pressures on the degradation of the PLA BVS. The results showed that the high pressure weakly accelerated the degradation of the PLA BVS with respect to the normal pressure by examining the four indexes, e.g., the residual stent volume decreased to 0.72 and 0.69, respectively for the normal and high pressures at day 180. The current finding provided a theoretical understanding of the PLA BVS degradation, and hinted that the PLA BVS may not need to be elaborately selected in clinical practices for treating hypertensive patients.

3D printed peripheral vascular stents based on degradable poly(trimethylene carbonate‐b‐(L‐lactide‐ran‐glycolide)) terpolymer

AbstractPoly(L‐lactic acid) (PLLA) is a biocompatible material and has found its application in bioresorbable vascular stents (BVS). However, the crystallization of pure PLLA makes it brittle as a medical implant device. In this work, the biodegradable poly(1,3‐trimethylene carbonate‐b‐(L‐lactide‐ran‐glycolide acid)) (PTLG) terpolymers with improved mechanical performance were developed and processed into peripheral vascular stents by a novel 3D 4‐axial printing technology. The PTLG terpolymers were successfully synthesized by ring‐opening copolymerization of L‐lactic acid (LLA), 1,3‐trimethylene carbonate (PTMC) and glycolide acid (GA) units. The crystallinity and mechanical properties of the PTLG terpolymers with various degradation rate depends on the chain sequence structure and the component contents. Compared with the stent prepared by laser engraving, the peripheral vascular stent prepared by the 3D 4‐axial printing technology exhibit a finer structure and smoother strut surface. It was found that both the strut diameters and the molecular weight of PTMC affect the radial force of the stents and that the apparent activation energy of thermal decomposition of the stents is mainly influenced by the molecular weight of PTMC and the component ratio. Therefore, the addition of the PTMC segment can effectively improve the flexibility of the PTLG terpolymer stent and the 3D printed PTLG terpolymer‐based stent. Furthermore, CCK‐8 and live/dead staining suggested that the stents have good biocompatibility.

Photocurable Nitric Oxide-Releasing Copolyester for the 3D Printing of Bioresorbable Vascular Stents.

The design of bioresorbable vascular stents (BVS) capable of releasing nitric oxide (NO) at the implant site may enable BVS to mimic the antiplatelet, antiproliferative, and pro-endothelial actions of NO, overcoming complications of BVS such as late thrombosis and restenosis. In this study, the fabrication of BVS composed of methacrylated poly(dodecanediol citrate-co-dodecanediol S-nitroso-mercaptosuccinate) (mP(DC-co-DMSNO)), a novel elastomeric, bioabsorbable, and photocurable copolyester, containing covalently bound S-nitrosothiol groups in the carbon backbone of the polymer, is reported. The mP(DC-co-DMSNO) stents are manufactured via photoinduced 3D printing and allow deployment via a self-expansion process from a balloon catheter. After deployment, hydration of the stents triggers the release of NO, which is maintained during the slow hydrolysis of the polymer. Real-time NO release measurements show that by varying the copolyester composition and the strut geometry of the mP(DC-co-DMSNO) stents, it is possible to modulate their NO release rate in the range of 30-52pmol min-1 cm-2 . Preliminary biological assays in cell culture show that endothelial cells adhere to the surface of the stents and that NO release favors their endothelization. Thus, mP(DC-co-DMSNO) may emerge as a new platform for the fabrication of advanced BVS.

Incorporating Copper to Biodegradable Magnesium Alloy Vascular Stents via a Cu(II)‐Eluting Coating for Synergistic Enhancement in Prolonged Durability and Rapid Re‐Endothelialization

AbstractBiodegradable magnesium‐based scaffolds present outstanding potential to revolutionize the treatment of coronary artery diseases, in which full recovery of arteries without long‐term irritation of implants is anticipated for averting adverse events associated with the permanent stents. However, overfast degradation of magnesium (Mg) alloys obstructs their extensive applications in terms of early structural failure and impaired biocompatibility. Herein, a facile copper‐incorporated coating system through nonaqueous phase synthesis of polydopamine is developed to facilitate Cu(II) capture along with robust film deposited on easily corrodible Mg, which subsequently enables sustained Cu(II) elution. It remarkably enhances corrosion resistance and impedes Mg degradation, which also contributes to improved, superior cytocompatibility, and abolished hemolysis. Moreover, through simultaneous control of Cu(II) and Mg(II) release to modulate the local microenvironment, a synergistic biochemical effect on desirable vascular cell selectivity is triggered for boosted endothelial cell viability and suppressed smooth muscle cell. Stent implantation into rabbit abdominal aorta thus exhibits accelerated re‐endothelialization completed in a week, and enhanced biological outcomes, alleviated complications and prolonged structural durability in 3‐month follow‐up. Collectively, this study opens up an alternative route of deploying a multifunctional surface modification strategy tailoring active interplay with the Mg matrix for better outcomes of next‐generation bioresorbable vascular stents.

3D Printing of Polymeric Bioresorbable Stents: A Strategy to Improve Both Cellular Compatibility and Mechanical Properties.

One of the leading causes of death is cardiovascular disease, and the most common cardiovascular disease is coronary artery disease. Percutaneous coronary intervention and vascular stents have emerged as a solution to treat coronary artery disease. Nowadays, several types of vascular stents share the same purpose: to reduce the percentage of restenosis, thrombosis, and neointimal hyperplasia and supply mechanical support to the blood vessels. Despite the numerous efforts to create an ideal stent, there is no coronary stent that simultaneously presents the appropriate cellular compatibility and mechanical properties to avoid stent collapse and failure. One of the emerging approaches to solve these problems is improving the mechanical performance of polymeric bioresorbable stents produced through additive manufacturing. Although there have been numerous studies in this field, normalized control parameters for 3D-printed polymeric vascular stents fabrication are absent. The present paper aims to present an overview of the current types of stents and the main polymeric materials used to fabricate the bioresorbable vascular stents. Furthermore, a detailed description of the printing parameters’ influence on the mechanical performance and degradation profile of polymeric bioresorbable stents is presented.

Improved mechanical properties of poly(l‐lactic acid) stent coated by poly(d, l‐lactic acid) and poly(l‐lactic‐co‐glycolic acid) biopolymer blend

AbstractBiopolymer coating is widely used in stent for drug delivery while few researches relate to its effect on mechanical properties. The strategy of blending poly(d, l‐lactic acid) (PDLLA) and poly(l‐lactic‐co‐glycolic acid) (PLGA) (100/0, 80/20, 50/50, wt/wt) was adopted in this study to explore solutions. Experiments on radial force, bending stiffness and surface morphology of poly(L‐lactic acid) stents were carried out to study the comprehensive influence of coatings with different formulations on the mechanical properties of stents. Results suggested that stents coated with PDLLA/PLGA (80/20) have shown the most superior radial supporting performance and axial flexibility. Moreover, scanning electron microscopic image of surface morphology of stents showed reliable adhesion between the coatings and stents. This study can provide a feasible method for improving the mechanical properties of bioresorbable vascular stents.

3D printed bioresorbable nitric oxide-releasing vascular stents

Although bioresorbable vascular stents (BVS) have emerged as a promising alternative to overcome complications of metallic stents, adverse outcomes of BVS demand further improvements. The development of photocrosslinkable polyesters, such as methacrylated poly(dodecanediol citrate) (mPDC) for use in light-assisted 3D printing technologies, brought new perspectives for the fabrication of BVS. In line with this approach, the knowledge of the pro-endothelial and anti-thrombotic actions of nitric oxide (NO), has stimulated the development of NO-releasing BVS. Herein, we describe the fabrication of mPDC-based NO-releasing BVS, using digital light processing (DLP) 3D printing. The NO release property of the mPDC matrix was obtained through the incorporation of the NO donor S-nitroso-N-acetyl-d-penicillamine (SNAP). Chemiluminescent real-time NO detection showed that NO release from mPDC/SNAP is triggered by contact with the aqueous medium at rates which can be modulated by the SNAP charge. The obtained NO release rates, in the range of 20–160 ​pmol ​cm−2 min−1, have potential to inhibit thrombus formation. Therefore, 3D printed BVS made of NO-releasing mPDC/SNAP may offer a simple and new strategy for overcoming late thrombotic complications of BVS.

Biocompatibility analysis of PLA based candidate materials for cardiovascular stents in a rat subcutaneous implant model

Modification of Polylactic acid (PLA), a biopolymer, is a strategy still to be fully explored for the next generation of bioresorbable vascular stent (BVS) biomaterials. With this focus, inclusions upto 5% of Polycaprolactone (PCL) and Magnesium in PLA were tested in the rat subcutaneous model and their cellular and tissue interactions characterized, specifically with respect to inflammatory response, angiogenesis and capsularization. The cytokines IL6, TNF Alpha and IL-1Beta were estimated in the peri-implant tissue, all of which showed a non-significant difference between the non-implanted animals and those containing PLA by 8 weeks, speaking to the benign nature of PLA as an implant biomaterial. Both modified materials, had increased macrophage counts and cytokine levels, except IL6 at 8 weeks. Vascularization only at 8 weeks in PLA PCL containing tissue was significantly higher than pure PLA, which may be more carefully controlled along with the material hydrophobicity for possible efforts towards therapeutic angiogenesis. Capsule thickness, measured by staining with both Hematoxylin & Eosin and Masson’s Trichome did not show any differences between materials, including PLA.

Cytocompatibility Evaluation of a Novel Series of PEG-Functionalized Lactide-Caprolactone Copolymer Biomaterials for Cardiovascular Applications.

Although the use of bioresorbable materials in stent production is thought to improve long-term safety compared to their durable counterparts, a recent FDA report on the 2-year follow-up of the first FDA-approved bioresorbable vascular stent showed an increased occurrence of major adverse cardiac events and thrombosis in comparison to the metallic control. In order to overcome the issues of first generation bioresorbable polymers, a series of polyethylene glycol-functionalized poly-L-lactide-co-ε-caprolactone copolymers with varying lactide-to-caprolactone content is developed using a novel one-step PEG-functionalization and copolymerization strategy. This approach represents a new facile way toward surface enhancement for cellular interaction, which is shown by screening these materials regarding their cyto- and hemocompatibility in terms of cytotoxicity, hemolysis, platelet adhesion, leucocyte activation and endothelial cell adhesion. By varying the lactide-to-caprolactone polymer composition, it is possible to gradually affect endothelial and platelet adhesion which allows fine-tuning of the biological response based on polymer chemistry. All polymers developed were non-cytotoxic, had acceptable leucocyte activation levels and presented non-hemolytic (<2% hemolysis rate) behavior except for PLCL-PEG 55:45 which presented hemolysis rate of 2.5% ± 0.5. Water contact angles were reduced in the polymers containing PEG functionalization (PLLA-PEG: 69.8° ± 2.3, PCL-PEG: 61.2° ± 7.5) versus those without (PLLA: 79.5° ± 3.2, PCL: 76.4° ± 10.2) while the materials PCL-PEG550, PLCL-PEG550 90:10 and PLCL-PEG550 70:30 demonstrated best endothelial cell adhesion. PLLA-PEG550 and PLCL-PEG550 70:30 presented as best candidates for cardiovascular implant use from a cytocompatibility perspective across the spectrum of testing completed. Altogether, these polymers are excellent innovative materials suited for an application in stent manufacture due to the ease in translation of this one-step synthesis strategy to device production and their excellent in vitro cyto- and hemocompatibility.

The effect of intrinsic characteristics on mechanical properties of poly(l-lactic acid) bioresorbable vascular stents

Poly(L-lactic acid) (PLLA) is currently the bioresorbable polymer of choice for vascular stents with its superior biocompatibility and mechanical properties. However, it is still difficult to enhance the radial supporting capacity of PLLA stents without increasing the strut thickness. In this study, the performance of laser-cut thin-strut stents from two groups of PLLA tubes are investigated. We considered two groups of PLLA tubes. Group 1 indicates the longitudinally stretched from original 150-μm-thick tubes, and Group 2 indicates the directly thinned from original 150-μm-thick tubes. Three stages of mechanical tests were conducted in this study, which are defined as tensile tests of dog-bone specimens, radial loading tests of tubes and radial loading tests of stents. The results suggest that Group 2 has higher radial supporting capacity than Group 1 with the same wall thickness. This work serves as a basis for manufacturing thin-strut stents with sufficient radial supporting capacity.

Bioresorbable vascular stents and drug-eluting stents in treatment of coronary heart disease: a meta-analysis

ObjectiveTo compare the efficacy and safety of bioresorbable vascular stents (BVS) and drug-eluting stents (DES) in coronary heart disease.MethodsThe full text of clinical studies involving BVS and DES was retrieved in PubMed, Springer, EMBASE, Wiley-Blackwell, and Chinese Journal Full-text Database. Review Manager 5.3 was used for meta-analysis to evaluate the risk of target lesion failure, stent thrombosis and cardiac death in BVS and DES.ResultsFinally, 10 studies with 6383 patients were included in the meta-analysis. Compared with DES group, BVS group had significantly increased risk of target lesion failure (OR = 1.46, 95%CI 1.20–1.79, P = 0.0002; P Heterogeneity = 0.68, I2 = 0%), stent thrombosis (OR = 2.70, 95%CI 1.57–4.66, P = 0.0003; P Heterogeneity = 1.00, I2 = 0%) and cardiac death (OR = 2.19, 95%CI 1.17–4.07, P = 0.01; P Heterogeneity = 0.93, I2 = 0%).ConclusionThis study shows that DES is a safer treatment than BVS for coronary revascularization.

Atomic Layer Deposition Coating of TiO2 Nano-Thin Films on Magnesium-Zinc Alloys to Enhance Cytocompatibility for Bioresorbable Vascular Stents.

Background and purposeA coronary stent is a well-known cardiovascular medical device implanted to resolve disorders of the circulatory system due to bloodstream narrowing. Since the implanted device interacts with surrounding biological environments, the surface properties of a typical implantable stent play a critical role in its success or failure. Endothelial cell adhesion and proliferation are fundamental criteria needed for the success of a medical device. Metallic coronary stents are commonly used as biomaterial platforms in cardiovascular implants. As a new generation of coronary stents, bioresorbable vascular scaffolds have attracted a great deal of attention among researchers and studies on bioresorbable materials (such as magnesium and zinc) remain a target for further optimization. However, additional surface modification is needed to control the biodegradation of the implant material while promoting biological reactions without the use of drug elution.MethodsHerein, precise temperature and thickness controlled atomic layer deposition (ALD) was utilized to provide a unique and conformal nanoscale TiO2 coating on a customized magnesium-zinc stent alloy.ResultsImpressively, results indicated that this TiO2 nano-thin film coating stimulated coronary arterial endothelial cell adhesion and proliferation with additional features acting as a protective barrier. Data revealed that both surface morphology and surface hydrophilicity contributed to the success of the ALD nanoscale coating, which further acted as a protection layer inhibiting the release of harmful degradation products from the magnesium-zinc stent.ConclusionOverall, the outcome of this in vitro study provided a promising ALD stent coating with unique nano-structural surface properties for increased endothelialization, and as a result, ALD should be further studied for numerous biomedical applications.

Textile fabricated biodegradable composite stents with core-shell structure

This study proposes composite stents with core–shell structure. Biodegradable polyvinyl alcohol (PVA) yarns are twisted and then coated with polycaprolactone/polyethylene glycol (PEG) blends. The coated yarns are weft knitted into braids and then thermally treated to form composite stents with core–shell structure. The morphological, mechanical, and biological characteristics of the formed composite stents are evaluated to determine the effects of PEG concentration. Results show that composite stents acquire the flexibility of PVA yarns and elasticity of weft knits. The presence of PEG positively influences composite stent performance. When the PEG concentration is 30 wt%, composite stents exhibit a compressive strength of 6.15 N and cell viability of 97.32% after a 24 h of culture. The selected materials are biodegradable, and the novel structure meets the requirements of bioresorbable vascular stent, which suggests that the proposed composite stents have good potential for advancement.

Zn-alloy provides a novel platform for mechanically stable bioresorbable vascular stents.

Metallic Zn alloys have recently gained interest as potential candidates for developing platforms of bioresorbable vascular stents (BVS). Previous studies revealed that Mg alloys used for BVS can degrade too early, whereas PLLA materials may fail to provide effective scaffolding properties. Here we report on results of a new bioresorbable, metallic stent made from a Zn-Ag alloy studied in a porcine animal model of thrombosis and restenosis. While the tensile strength (MPa) of Zn-3Ag was higher than that of PLLA and resembled Mg’s (WE43), fracture elongation (%) of Zn-3Ag was much greater (18-fold) than the PLLA’s or Mg alloy’s (WE43). Zn-3Ag exposed to HAoSMC culture medium for 30 days revealed degradation elements consisting of Zn, O, N, C, P, and Na at a 6 nm surface depth. Platelet adhesion rates and blood biocompatibility did not differ between Zn-3Ag, PLLA, Mg (WE43), and non-resorbable Nitinol (NiTi) stent materials. Balloon-expandable Zn-3Ag alloy BVS implanted into iliofemoral arteries of 15 juvenile domestic pigs were easily visible fluoroscopically at implantation, and their bioresorption was readily detectable via X-ray over time. Histologically, arteries with Zn-3Ag BVS were completely endothelialized, covered with neointima, and were patent at 1, 3, and 6 months follow-up with no signs of stent thrombosis. Zn-3Ag alloy appears to be a promising material platform for the fabrication of a new generation of bioresorbable vascular stents.

Surface patterning of a novel PEG-functionalized poly-l-lactide polymer to improve its biocompatibility: Applications to bioresorbable vascular stents.

Today, research in the field of bioresorbable vascular stents (BVS) not only focusses on a new material being nontoxic but also tries to enhance its biocompatibility in terms of endothelialization potential and hemocompatibility. To this end, we used picosecond laser ablation technology as a single‐step and contactless method for surface microstructuring of a bioresorbable polymer which can be utilized in stent manufacture. The method works on all materials via fast material removal, can be easily adapted for micropatterning of tubular or more complex sample shapes and scaled up by means of micropatterning of metal molds for manufacturing. Here, picosecond laser ablation was applied to a bioresorbable, biologically inactive and polyethylene glycol‐modified poly‐l‐lactide polymer (PEGylated PLLA) to generate parallel microgrooves with varying geometries. The different patterns were thoroughly evaluated by a series of cyto‐ and hemocompatibility tests revealing that all surfaces were non‐toxic and non‐hemolytic. More importantly, patterns with 20 to 25 µm wide and 6 to 7 µm deep grooves significantly enhanced endothelial cell adhesion in comparison to samples with smaller grooves. Here, human cardiac microvascular endothelial cells were found to align along the groove direction, which is thought to encourage endothelialization of intraluminal surfaces of BVS. © 2018 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000–000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 624–634, 2019.

Are Bioresorbable Stents Ready for Primetime

Theoretical advantages of drug-eluting, fully bioresorbable vascular stents (BVS) over standard metallic ones (DES) may include better vessel healing

Quantitative multi-modality imaging analysis of a fully bioresorbable stent: a head-to-head comparison between QCA, IVUS and OCT

The bioresorbable vascular stent (BVS) is totally translucent and radiolucent, leading to challenges when using conventional invasive imaging modalities. Agreement between quantitative coronary angiography (QCA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in the BVS is unknown. Forty five patients enrolled in the ABSORB cohort B1 study underwent coronary angiography, IVUS and OCT immediately post BVS implantation, and at 6 months. OCT estimated stent length accurately compared to nominal length (95% CI of the difference: −0.19; 0.37 and −0.15; 0.47 mm2 for baseline and 6 months, respectively), whereas QCA incurred consistent underestimation of the same magnitude at both time points (Pearson correlation = 0.806). IVUS yielded low accuracy (95% CI of the difference: 0.77; 3.74 and −1.15; 3.27 mm2 for baseline and 6 months, respectively), with several outliers and random variability test–retest. Minimal lumen area (MLA) decreased substantially between baseline and 6 months on QCA and OCT and only minimally on IVUS (95% CI: 0.11; 0.42). Agreement between the different imaging modalities is poor: worst agreement Videodensitometry-IVUS post-implantation (ICCa 0.289); best agreement IVUS-OCT at baseline (ICCa 0.767). All pairs deviated significantly from linearity (P < 0.01). Passing-Bablok non-parametric orthogonal regression showed constant and proportional bias between IVUS and OCT. OCT is the most accurate technique for measuring stent length, whilst QCA incurs systematic underestimation (foreshortening) and solid state IVUS incurs random error. Volumetric calculations using solid state IVUS are therefore not reliable. There is poor agreement for MLA estimation between all the imaging modalities studied, including IVUS-OCT, hence their values are not interchangeable.Electronic supplementary materialThe online version of this article (doi:10.1007/s10554-011-9829-y) contains supplementary material, which is available to authorized users.