Biodegradable Drug-eluting Stents Research Articles

Animal model assessment of a new design for a coated mitomycin-eluting biodegradable ureteral stent for intracavitary instillation as an adjuvant therapy in upper urothelial carcinoma.

A major limitation in the treatment of upper urinary tract urothelial carcinoma is the limited use of adjuvant therapy due to the drawbacks of current techniques for intracavitary instillation. The aim was to assess, in a large animal model, a biodegradable ureteral stent coated with silk fibroin for mitomycin release, i.e. BraidStent-SF-MMC. A total of 14 female pigs with a solitary kidney underwent initial urinalysis, blood chemistry, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Later, the BraidStent-SF-MMC was placed retrogradely to assess the mitomycin urine concentration from 0-48 hours. Follow-up was performed weekly until complete stent degradation to assess the macroscopic and microscopic changes in the urinary tract, stent complications. The drug eluting stent released mitomycin for the first 12 h. The main complication was the release of obstructive ureteral coating fragments during the first to third week in 28.5 and 7.1% of animals, respectively, related to urinary pH<7.0, which destabilized the stent coating. Another complication was ureteral strictures between the fourth and sixth week in 21%. The stents were completely degraded by 6-7 weeks. There were no stent-related systemic toxic effects. The success rate was 67.5% and the complication rate was 25.7%. For the first time, we have shown that a biodegradable anti-cancer drug eluting stent, BraidStent-SF-MMC, provides controlled and well-tolerated release of mitomycin into the upper urinary tract in an animal model. Mitomycin release from a silk fibroin coating could be a compelling approach for adjuvant chemotherapy instillation in upper tract urothelial carcinoma management.

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.

MP094 - In vitro assessment of new ureteral biodegradable drug eluting stent design to adjuvant therapy in upper tract urothelial carcinoma

MP094 - In vitro assessment of new ureteral biodegradable drug eluting stent design to adjuvant therapy in upper tract urothelial carcinoma

The Exploration of a Novel Biodegradable Drug-Eluting Biliary Stent: Preliminary Work.

To explore the degradation, drug release, and mechanical properties of drug-incorporated films made of different ratios of poly(lactic-co-glycolic acid) (PLGA) and different amounts of paclitaxel (PTX), which may serve as the material platform for the manufacturing of biodegradable drug-eluting biliary stents. PLGA of different lactic acid/glycolic acid ratios (50/50, 70/30, and 80/20) and 0%, 10, 20, and 30% weight by weight (w/w) PTX was mixed to make PLGA films, which were then cut into small pieces for further testing. Films were immersed in phosphate-buffered saline (pH 7.4) for a maximum of 11weeks. Samples were taken randomly at Day 2, 4, 6, 8, 10, 12, 14, and weekly thereafter until Week 11 to test tensile strength, weight loss, pH value of the soaking solution, and drug release. The morphology of films was observed using scanning electron microscope (SEM). At Week 10 of degradation, PLGA 80/20 still withstood a tensile strength of 9.7newton (N), while PLGA 50/50 and 70/30 cracked spontaneously since Day 4. At Week 11, weight loss of PLGA 50/50, 70/30, and 80/20 was 95.15, 82.32, and 16.17%, respectively; and the lowest pH value of soaking solution was 1.87, 1.95, and 6.58, respectively. Drug release of 10, 20, and 30% PTX groups was 3.52-4.48%, 1.90-2.26%, and 1.44-2.06%, respectively. SEM proved smooth films before degradation; however, after the tensile strength was lost, cracks could be seen. The degradation rate of PLGA can be controlled by altering lactic acid/glycolic acid ratio. Overall, PLGA 50/50 and 70/30 degrade significantly faster than 80/20. PLGA can serve as an effective drug carrier for PTX while being the stent strut, and PTX can be slowly released as PLGA degrades.

Late neointimal volume reduction is observed following biodegradable polymer-based drug eluting stent in porcine model.

BackgroundThe BP-SES has an abluminally applied biodegradable polymer that is fully resorbed after 3–4 months but may have longer-lasting effects. The aim of this study was to determine the long-term vascular response to the novel Ultimaster™ sirolimus-eluting stent (BP-SES).MethodsBP-SESs, everolimus-eluting stents (DP-EESs), and bare metal stents were implanted in 22 coronary arteries of 15 mini-swine. All animals underwent optical frequent domain imaging (OFDI) to assess neointimal volume and quality at either 1 (n = 7) or 3 (n = 8) months and at 9 (n = 15) months and were euthanized at 9 months. Stents were subsequently histologically investigated to analyze the vascular response and maturity of neointimal tissue according to cell density.ResultsOFDI revealed greater regression in neointimal volume from 3 to 9 months with BP-SESs than with DP-EESs (−0.6 ± 0.5 mm2 vs. 0.00 ± 0.4 mm2, p = 0.07). Although there was no significant difference between BP-SESs and DP-EESs in the inflammation score (BMS, BP-SES, and DP-EES: 0.1 ± 0.1, 0.3 ± 0.4, and 0.4 ± 0.4, respectively; p < 0.0001) in histological analysis, BP-SESs showed slightly greater maturity than DP-EESs (1.8 ± 0.3, 1.7 ± 0.3, and 1.6 ± 0.3, p = 0.09).ConclusionsWhile both BP-SESs and DP-EESs showed minimal inflammatory responses at 9 months, BP-SESs showed a trend for greater neointimal maturity and regression, which may be related to earlier completion of the vascular response.

An asymmetric surface coating strategy for improved corrosion resistance and vascular compatibility of magnesium alloy stents

Magnesium (Mg) and its alloys are promising materials for biodegradable drug-eluting stent applications, but their rapid corrosion remains a major challenge for clinical practice. Considerable efforts have been made to develop an efficient surface coating that can provide higher Mg stent corrosion resistance, sustained drug-delivery capability, and vascular compatibility. Herein, we introduce poly(ether imide) (PEI) and poly(lactic-co-glycolic acid) (PLGA) as surface coating polymers for WE43 Mg-alloy stent. Using a sequential spray-coating method, we developed a novel asymmetric stent coating comprising an inner surface coated with a PEI single layer and outer/side surfaces coated with sirolimus-loaded PLGA/PEI double layers. PEI coating layer has excellent adhesiveness to WE43 surface and considerably improves WE43 corrosion resistance and in vitro endothelial cell compatibility. PLGA/PEI double coating layer ensures a low release rate of sirolimus and stable surface morphology during drug-release process. Only vascular smooth muscle cells are directly affected by sirolimus owing to the asymmetric geometry of PLGA/PEI double coating, which has a satisfactory anti-proliferation effect. These results indicate that the developed asymmetrically PEI- and PLGA/PEI-coated WE43 stents have significant potential for achieving enhanced re-endothelialization and suppressed in-stent restenosis in vascular stent applications.

Biodegradable drug-eluting urethral stent in limiting urethral stricture formation after urethral injury: An experimental study in rabbit

In this study, a reproducible urethral injury animal model was developed and the role of the biodegradable drug-eluting urethral stent in limiting urethral stricture formation after urethral injury was evaluated. A total of 22 rabbits were used, and 20 rabbits were randomly chosen to develop urethral injury animal model. Bulbar urethral injury was made by a self-designed explosion device in the 20 rabbits. The urethral injury animal model was then randomly assigned to 2 groups of 10 each, which received a treatment of biodegradable paclitaxel-eluting urethral stent or only end-to-end anastomosis. Other two rabbits served as normal control group. Stents were surgically implanted into the injured urethras of rabbits under direct vision. Reparative effects, including stent degradation, were evaluated by urethroscopy, retrograde urethrography, and histology at different intervals at weeks 4, 8, and 12. In stent-free group, 8 of 10 rabbits developed obvious urethral stricture which was demonstrated by urethroscopy and retrograde urethrography, while in biodegradable paclitaxel-eluting stent group, urethral stricture was absent in all animals (p &lt; 0.05). Histological follow-up indicated that the drug-eluting stents can also minimize the inflammatory reactions and fibrosis formation compared with the stent-free groups. Scanning electron microscope demonstrated that the biodegradable drug-eluting stent can gradually degrade in 12 weeks. The biodegradable paclitaxel-eluting urethral stent is effective in limiting urethral stricture formation after urethral injury.

Biodegradable MRI Visible Drug Eluting Stent Reinforced by Metal Organic Frameworks.

Metal-organic frameworks (MOFs) have applications in numerous fields. However, the development of MOF-based "theranostic" macroscale devices is not achieved. Here, heparin-coated biocompatible MOF/poly(ε-caprolactone) (PCL) "theranostic" stents are developed, where NH2 -Materials of Institute Lavoisier (MIL)-101(Fe) encapsulates and releases rapamycin (an immunosuppressive drug). These stents also act as a remarkable source of contrast in ex vivo magnetic resonance imaging (MRI) compared to the invisible polymeric stent. The in vitro release patterns of heparin and rapamycin respectively can ensure a type of programmed model to prevent blood coagulation immediately after stent placement in the artery and stenosis over a longer term. Due to the presence of hydrolysable functionalities in MOFs, the stents are shown to be highly biodegradable in degradation tests under various conditions. Furthermore, there is no compromise of mechanical strength or flexibility with MOF compositing. The system described here promises many biomedical applications in macroscale theranostic devices. The use of MOF@PCL can render a medical device MRI-visible while simultaneously acting as a carrier for therapeutic agents.

Slicing parameter optimization for 3D printing of biodegradable drug-eluting tracheal stents

In 3D printing, the schematic representation of an object must be converted into machine commands. This process is called slicing. Depending on the slicing parameters, products with different properties are obtained. In this work, biodegradable drug-eluting tracheal stents consisting of a medical grade poly(lactic-co-glycolic acid) and a drug were printed by fused deposition modeling. A slicing parameter optimization method was proposed with the aim of obtaining a particularly low stent porosity and high mechanical strength while maintaining the stent dimensions, which is essential regarding patient-tailored implants. Depending on the three slicing parameters printing pattern, lateral strand distance and spatial fill, porosities of approximately 2–5% were obtained. The tensile strength was used as a measure for the mechanical strength of the implants and was found to be dependent on the porosity as well as the strand orientation relative to the load direction. Strand orientations in load direction yielded the highest tensile strengths of 40–46 MPa and the bonding between individual layers yielded the lowest tensile strengths of 20–24 MPa. In vitro dissolution tests of successfully printed stents were used to predict sustained release of the drug over several months.

An Overview of the Design, Development and Applications of Biodegradable Stents

Background &amp; Objectives: Stents have been effectively used in the treatment of vascular diseases and further explorations are going on in treating various strictures including tracheal, intestinal, nasal, urethra and esophageal. Stents serve as a support to walls of the lumen to prevent restenosis. Metal stents prevent in-stent restenosis but the corrosion of the metallic framework causes further complications. To overcome the shortcomings of metallic stents, metallic Drug-Eluting Stents (DES) have been designed where the drugs are chosen as an anti-restenosis agent in such a way that it prevents thrombosis, neointimal proliferation and possess immunosuppressive properties. Biodegradable stents are becoming ideal, provided they effectively spot the target stricture and have long-term stability to support the walls of the body conduit which in turn aids in eliminating the need for a second surgery. Polymeric materials can be used to enhance the mechanical strength and prolong the degradation time of biodegradable DES, thereby making it an ideal choice for stenting. Discussion: This review focus on the progress made in the design, manufacture, characterization studies and applications of stents over the past decade. Conclusion: We concluded that the use of stents is now an emerging technique for the treatment of GI strictures caused due to colorectal cancer, esophageal cancer, cholangiocarcinoma, Crohn’s disease etc. Though BDS have several advantages, advanced techniques are needed for fabrication and suitable modification in the design of the scaffold to enhance its clinical efficacy and to thereby develop an ideal endoprosthetic device.

Rapamycin-loaded nanoporous α-Fe2O3 as an endothelial favorable and thromboresistant coating for biodegradable drug-eluting Fe stent applications.

Iron and its alloys can be potentially employed to fabricate advanced degradable cardiovascular stents due to their excellent mechanical and biocompatibility properties. However, their clinical applications are hindered by their inherent slow degradation rate, the formation of thrombosis and in-stent restenosis. In this study, vertically oriented and orderly arranged α-Fe2O3 (hematite) nanotubes with diameters ranging from 30 nm to 70 nm were successfully fabricated on iron substrates using an anodic oxidation approach. These nanotubular coatings acted as drug depots by being loaded with anti-proliferation drug rapamycin to accelerate the re-endothelialization process and being coated by PLGA through a simple spin-coating process to control the drug release rate. The static immersion test showed that the 50 nm-Fe2O3 nanotube arrays displayed a faster corrosion rate than pristine Fe, and the PLGA coating effectively reduced the initial burst release of the loaded drug and extended the rapamycin release time to 30 days. The CCK-8 assay and immunofluorescence staining analysis results indicated that the endothelial cells (ECs) on the coated samples showed higher cell viability than the vascular smooth muscle cells (VSMCs), with possible outcomes to promote re-endothelialization and decrease VSMC proliferation. In addition, the surface modified iron exhibited very good hemocompatibility. The current findings suggested that fabricating rapamycin-loaded and PLGA coated Fe2O3 nanotubes on a pure iron surface may be a promising method to improve the corrosion rate and accelerate the re-endothelialization of the iron for biodegradable cardiovascular stent applications.

TCT-427 Comparison of Neointimal Coverage Patterns between Biodegradable Vascular Stents and Drug Eluting Stents using Optical Coherence tomography: A Meta-Analysis

TCT-427 Comparison of Neointimal Coverage Patterns between Biodegradable Vascular Stents and Drug Eluting Stents using Optical Coherence tomography: A Meta-Analysis

046 - Upper urinary tract urothelial tumours targeted with biodegradable drug-eluting stents

046 - Upper urinary tract urothelial tumours targeted with biodegradable drug-eluting stents

Polymeric Biodegradable Stent Insertion in the Esophagus.

Esophageal stent insertion has been used as a well-accepted and effective alternative to manage and improve the quality of life for patients diagnosed with esophageal diseases and disorders. Current stents are either permanent or temporary and are fabricated from either metal or plastic. The partially covered self-expanding metal stent (SEMS) has a firm anchoring effect and prevent stent migration, however, the hyperplastic tissue reaction cause stent restenosis and make it difficult to remove. A fully covered SEMS and self-expanding plastic stent (SEPS) reduced reactive hyperplasia but has a high migration rate. The main advantage that polymeric biodegradable stents (BDSs) have over metal or plastic stents is that removal is not require and reduce the need for repeated stent insertion. But the slightly lower radial force of BDS may be its main shortcoming and a post-implant problem. Thus, strengthening support of BDS is a content of the research in the future. BDSs are often temporarily effective in esophageal stricture to relieve dysphagia. In the future, it can be expect that biodegradable drug-eluting stents (DES) will be available to treat benign esophageal stricture, perforations or leaks with additional use as palliative modalities for treating malignant esophageal stricture, as the bridge to surgery or to maintain luminal patency during neoadjuvant chemoradiation.

938 Biodegradable drug-eluting stents: Targeting urothelial tumors of upper urinary tract

938 Biodegradable drug-eluting stents: Targeting urothelial tumors of upper urinary tract

Study on the rapamycin release from a PLGA layer on biodegradable Mg-based drug-eluting stents

Study on the rapamycin release from a PLGA layer on biodegradable Mg-based drug-eluting stents

Development of a New Hybrid Biodegradable Drug-Eluting Stent for the Treatment of Peripheral Artery Disease.

This study aimed to develop a new biodegradable stent for peripheral artery disease (PAD) that could provide sufficient radial force to maintain long-term patency and flexibility. All self-expandable hybrid biodegradable stents were designed by using a knitting structure composed of poly-L-lactic acid (PLLA) and nitinol. Four different types of stents were implanted in 20 iliac arteries in 10 mini pigs as follows: a bare-metal stent (BMS) (group 1, n = 5), a drug-free hybrid stent (group 2, n = 5), a 50% (50 : 100, w/w) paclitaxel (PTX)/poly-lactide-co-glycolic acid (PLGA; fast PTX-releasing form) hybrid stent (group 3, n = 5), and a 30% (30 : 100, w/w) PTX/PLGA (slow PTX-releasing form) hybrid stent (group 4, n = 5). We performed follow-up angiography and intravascular ultrasonography (IVUS) at 4 and 8 weeks. In a comparison of groups 1, 2, 3, and 4, less diameter stenosis was observed in the angiographic analysis for group 4 at the 4-week follow-up (19.0% ± 12.7% versus 39.3% ± 18.1% versus 46.8% ± 38.0% versus 4.8% ± 4.2%, resp.; p = 0.032). IVUS findings further suggested that the neointima of the patients in group 4 tended to be lesser than those of the others. Our new biodegradable 30% PTX/PLGA (slow-releasing form) stent showed more favorable results for patency than the other stent types.

6-Month Follow-Up of a Novel Biodegradable Drug-Eluting Stent Composed of Poly-L-Lactic Acid and Amorphous Calcium Phosphate Nanoparticles in Porcine Coronary Artery.

We reported previously, in porcine coronary arteries, that the novel biodegradable PowerStent Absorb paclitaxel-eluting stent had improved and sustained structural strength and functional performance at one month post-implantation. To report the stent performance at 6-month follow-up. Six PowerStent Absorb and six TAXUS stents were randomly implanted in the left anterior descending and right coronary arteries of six Tibet miniature pigs. Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) images were obtained at the time of implantation (T0) and at 6 months (T6). Two animals were sacrificed at T6 for histopathological evaluation. At T6, QCA showed that the mean luminal vascular diameter (mLD) between the PowerStent and the TAXUS stents were similar (2.36 ± 0.38 vs. 2.61 ± 0.31, respectively). Based on the IVUS analysis, the mLD and the mean lumen cross-sectional area (mCSA) in the PowerStent-treated arteries were similar between T0 and T6 (mLD: 2.74 ± 0.13 vs. 2.70 ± 0.20 and mCSA: 6.81 ± 0.62 mm2 vs. 6.68 ± 0.94 mm2). Histopathology showed that the PowerStent stents were well apposed to the vessel wall with no recoil, strut fracture and thrombus formation. The stents were fully covered with a layer of endothelial cells. At six-month post-implantation, the PowerStent Absorb stents maintained their structural strength and functional performance. The development of restenosis was controlled, no stent thrombosis was observed and the stents were fully re-endothelialized. These results suggest the PowerStent Absorb stent is safe and effective for up to 6 months when implanted in porcine coronary arteries.

Vascular restoration: Is there a window of opportunity?

The usage of drug eluting stents (DES) has markedly reduced the rates of coronary revascularization procedures compared with bare metal stents (BMS). However, this technology still faces challenges in terms of the prevention of late stent thrombosis, major adverse cardiac events (MACE) progression, and the catch-up phenomenon of restenosis. Restoration of endothelial function upon after stenting, therefore, is the key to mitigating the risk of these toxicities and determining the level of the efficacy and safety of an implant. Review of the clinical studies of multiple DES, has suggested that there exists a window of opportunity, within the first two to three months after stent implantation, for restoring vascular function. If re-endothelialization reaches sufficient level within this period, vascular restoration can occur; however, if this opportunity is missed, re-endothelialization is unlikely to reach the level of endothelial maturation necessary to prevent the late stent thrombosis, MACE progression and the catch-up on restenosis. This hypothesis could aid in explaining variable clinical responses for revascularization treatments such as plain old balloon angioplasty (POBA), BMS, or DES. Patients could be grouped according to responses to the different treatment modalities: for Type 1 patients, POBA is sufficient and safe because they possess the capacity with effective endothelial response; for Type 2 patients, re-endothelialization occurs within the window but BMS are needed to maintain the arterial lumen open; for Type 3 individuals, overly accelerated vascular smooth muscle proliferation render sufficient re-endothelialization impossible. Designing based on this principle predicts that the next technology advancement for the interventional cardiology will not be biodegradable DES by default, but rather a DES that can spur early restoration of the endothelial function within the window period.

A coupled non-Fickian model of a cardiovascular drug delivery system.

A coupled non-Fickian model of a cardiovascular drug delivery system using a biodegradable drug-eluting stent is proposed. The numerical results are obtained using an implicit-explicit finite-element method. The influence of vessel stiffness on the transport of drug eluted from the stent is analysed. The results presented in this paper suggest new perspectives to adapt the drug delivery profile to the needs of the patient.