Bioresorbable Scaffold Research Articles

A Snapshot on Clinical Trials on Zotarolimus DES: A Repurposing Drug against Myocardial Infarction

AbstractMyocardial infarction is the permanent death (necrosis) of heart muscle caused by a lack of oxygen for an extended period of time (ischemia). Since the very first percutaneous transluminal coronary angioplasty was done 40 years ago, the science of interventional cardiology has advanced dramatically. The above progression began with a balloon catheter attached to a fixed wire, advancing to bare-metal stents, first-generation drug-eluting stents (DES), second- and third-generation biodegradable polymer-based DES. Ultimately, bioabsorbable stents are still in development. Zotarolimus is a new pharmacologic therapy with a similar reprint address; for example, the antirestenosis agent sirolimus has recently been investigated as part of a stent platform combined with a biomimetic phosphorylcholine and BioLINX polymer for its biological activity, as well as its usefulness as an antiproliferative agent. Several clinical trials have been conducted to assess the safety and efficacy of the zotarolimus drug-eluting stent (Z-DES). Medtronic Medical Devices, a global leader in medical technology (United States), and Abbot Global Health Care and Research began clinical trials on the Z-DES in 2002 and will continue through 2021 (INDIA). Endeavor (E-Zes), Resolute (R-Zes), Resolute Integrity (I-Zes), and Resolute Onyx are the different forms of Z-DES that Medtronic has tested in clinical trials. In comparison to other DES, Z-DES was found to be safe in these clinical trials done across multiple nations and in a diverse demographic. This review helps understand the overall clinical trial of Z-DES.

3D printed polymeric stent design: Mechanical testing and computational modeling

Polymer-based bioresorbable scaffolds (BRS) aim to reduce the long-term issues associated with metal stents. Yet, first-generation BRS designs experienced a significantly higher rate of clinical failures compared to permanent implants. This prompted the development of alternative scaffolds, such as the poly(L-lactide-co-ε-caprolactone) (PLCL) solvent-casted stent, whose mechanical performance has yet to be addressed. This study examines the mechanical behavior of this novel scaffold across a wide range of parallel and radial compression diameters. The analysis highlights the scaffold’s varying responses under different loading conditions and provides insights into interpreting simulation model parameters to accurately reflect experimental results.Stents demonstrated a parallel crush resistance of 0.11 N/mm at maximum compression, whereas the radial forces were significantly higher, reaching up to 1.80 N/mm. Additionally, the parallel test keeps the stent in the elastic regime, with almost no regions exceeding 50 MPa of stress, while the radial test causes significant structural deformation, with localized plastic strain reaching up to 30 %. Results showed that underestimating yield strain in computational models leads to discrepancies with experimental results, being 5 % the most accurate value for matching computational and experimental results for PLCL solvent-casted stents.This comprehensive approach is vital for optimizing BRS design and predicting clinical performance.

Differential properties of drug-eluting stents and bioresorbable scaffolds in photon-counting computed tomography.

Differential properties of drug-eluting stents and bioresorbable scaffolds in photon-counting computed tomography.

Application of 3D Printing to Design and Manufacture Pancreatic Duct Stent and Animal Experiments.

Objective: Postoperative pancreatic fistula (POPF) is a common and challenging complication following pancreaticoduodenectomy (PD), occurring in 2% to 46% of cases. Despite various pancreaticojejunostomy techniques, an effective method to prevent POPF has not been established. This study aimed to develop and evaluate a novel 3D-printed biodegradable pancreatic duct stent to simplify the surgical process of pancreaticojejunostomy, reduce anastomotic complexity, and minimize postoperative complications. Methods: Data from 32 patients undergoing total laparoscopic pancreaticoduodenectomy were utilized. Preoperative CT scans were transformed into 3D reconstructions to guide the design and printing of customized stents using polylactic acid (PLA). The stents were assessed for mechanical integrity, surface texture, and thermal stability. Animal experiments were conducted on 16 mini pigs, with the experimental group receiving the novel stent and the control group receiving traditional silicone stents. Results: The 3D-printed stents demonstrated accurate dimensional replication and mechanical reliability. In the animal experiments, the experimental group showed no significant difference in postoperative complications compared to the control group. At 4 weeks post-surgery, CT scans revealed well-healed anastomoses in both groups, with no significant inflammation or other complications. Histological examination and 3D reconstruction models confirmed good healing and device positioning in the experimental group. Conclusion: The 3D-printed biodegradable pancreatic duct stent offers a promising solution for pancreaticojejunostomy, with comparable safety and efficacy to traditional methods. Further research is needed to validate its clinical application.

Acute Implantation of a Bioresorbable Polymer Scaffold in Patients With Complete Thoracic Spinal Cord Injury: A Randomized Controlled Trial (INSPIRE 2.0).

Traumatic spinal cord injury (SCI) remains a devastating condition with no proven effective treatment options available. In a prior single-arm study of patients with thoracic complete SCI (INSPIRE; ClinicalTrials.gov, NCT02138110), acute implantation of an investigational bioresorbable polymer scaffold (Neuro-Spinal Scaffold [NSS]) appeared to be safe through 24 months postimplantation and was associated with an American Spinal Injury Association Impairment Scale (AIS) conversion rate that exceeded historical controls. Here, we evaluated whether NSS implantation demonstrates probable benefit for safety and neurological recovery in patients with thoracic complete SCI vs standard-of-care spine surgery. INSPIRE 2.0 was a randomized, controlled, parallel, multicenter study conducted at Level I trauma centers in the United States (ClinicalTrials.gov, NCT03762655; funded by InVivo Therapeutics Corporation). Patients with AIS grade A, thoracic (T2-T12), nonpenetrating SCI requiring spine surgery ≤7 days postinjury were randomized (1:1, computer-generated allocation) to undergo NSS implantation or spine surgery alone (control group). Patients and follow-up International Standards for Neurological Classification of SCI assessors were blinded. A predefined study success criterion required the proportion of patients with improvement of ≥1 AIS grade at 6 months postsurgery (primary endpoint) to be ≥20% higher in the NSS group than in the control group. Target enrollment was reached (N = 20) with 10 patients randomized and analyzed in each group. At 6 months postsurgery, an improvement in the AIS grade was reported in 2 NSS patients (20%; both to AIS C) and 3 control group patients (30%; to AIS B [n = 2] or AIS C [n = 1]). No serious or unanticipated adverse device effects were reported. The study was closed to further follow-up because of not meeting its primary endpoint. In this small group of patients with thoracic complete (AIS A) SCI, implantation of an intraparenchymal bioresorbable scaffold did not produce probable clinical benefit. However, this study provides evidence that surgical intervention in an injured spinal cord parenchyma may be performed safely.

A Prospective, Randomized Trial of Bioresorbable Polymer Drug-Eluting Stents Versus Fully Bioresorbable Scaffolds in Patients Undergoing Coronary Stenting

Background: The performance of an everolimus-eluting bioresorbable scaffold (BRS) was inferior to an everolimus-eluting metallic drug-eluting stent (DES) with permanent polymer, mainly due the mechanical features of BRS technology. The performance of BRS as compared to metallic DES with bioresorbable polymers remains unstudied. Methods: This prospective, randomized, multicenter, clinical trial enrolled patients who underwent coronary stenting for de novo coronary lesions. Patients were randomly assigned to bioresorbable polymer everolimus-eluting stents (BP-EES) or everolimus-eluting BRS. The primary endpoint was percentage diameter stenosis (in-device) at 6- to 8-month angiographic surveillance. The main secondary endpoint was the device-oriented composite endpoint (DOCE) of cardiac death/target vessel-myocardial infarction/target lesion revascularization assessed after 12 months and 5 years. Results: The trial was prematurely terminated after the enrollment of 117 of 230 patients (BP-EES, n = 60; BRS, n = 57) due to safety issues associated with BRS technology. The primary endpoint of in-device diameter stenosis at angiographic surveillance was 12.5 ± 7.7% with BP-EES versus 19.3 ± 16.5% with BRS (p = 0.01). The DOCE occurred in 5.0% in the BP-EES group versus 12.3% of patients in the BRS group (hazard ratio [HR] 2.48, 95% confidence interval [CI] 0.64–9.58, p = 0.19) after 12 months and in 11.7% in the BP-EES group versus 26.4% of patients in the BRS group (HR 2.38, 95% CI 0.97–5.84, p = 0.06) after 5 years. Conclusions: BP-EES showed superior mid-term angiographic performance compared with BRS. Clinical event rates did not differ significantly between the groups up to 5 years of follow-up. These results should be interpreted with caution in view of the premature discontinuation of the study.

One-month DAPT after biodegradable-polymer everolimus-eluting stent implantation in women at high-bleeding risk: Insights from the POEM trial.

We conducted a prespecified subanalysis of the POEM trial to assess the association between sex and clinical outcomes following a short 1-month dual-antiplatelet-therapy (DAPT) period after percutaneous coronary intervention (PCI) with bioresorbable polymer everolimus-eluting stent (BP-EES) among patients at high bleeding risk (HBR). Shortening the DAPT period after PCI is an effective bleeding avoidance strategy with contemporary drug-eluting stents. Whether sex affects the risk of adverse events following PCI is still debated. Patients at HBR undergoing PCI with BP-EES were enrolled and treated with 1-month DAPT. If anticoagulation was needed, study participants received an oral anticoagulant (OAC) in addition to a P2Y12 inhibitor for 1 month, followed by OAC only thereafter. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. We report sex-based outcomes of patients included in the POEM study. We enrolled 129 (29.1%) women and 314 (70.9%) men. Women were older, with lower hemoglobin levels, and worse renal function. Accordingly, they had a trend for a greater number of HBR criteria fulfilled and a higher PARIS bleeding score. However, they were not at a significantly higher risk for the primary endpoint (men vs. women: 5.17% vs. 3.94%; HR 1.30; 95% CI: 0.48-3.54, p = 0.61), or any of the hemorrhagic and ischemic secondary endpoints. This prespecified subanalysis of the POEM trial suggests that 1-month DAPT following PCI with BP-EES may be a safe and effective therapeutic strategy for women at HBR.

Less is more: The use of a single biodegradable stenting to treat biliary anastomotic strictures in pediatric liver transplantation.

To report our experience of using biodegradable biliary stents for anastomotic biliary strictures in pediatric liver transplant patients. Analysis of a retrospective data collection from January 2014 to January 2023, including all pediatric liver transplant recipients in our center treated for anastomotic biliary strictures with biodegradable biliary stents (BBS). In phase 1 (2014-2019), there was an initial percutaneous transhepatic cholangiography (PTC) with anastomotic dilatation followed two weeks after by a second PTC with BBS insertion. In phase 2 (2019-2023), the BDS were placed shortly after anastomotic biliary strictures dilatation, requiring only one PTC. All patients were followed up with routine tests and ultrasound. Forty-six anastomotic biliary strictures were diagnosed in 43 pediatric liver transplant recipients with a median of 6.7 months post-liver transplantation (0.1-246.8 months). Eight out of 46 anastomotic biliary strictures (17.4%) treated with biodegradable biliary stents relapsed (median recurrence time: 6.5 months; 1.6-17.0 months). Four resolved with further BBS placement; only four needed surgical revision (8.7%) after a median follow-up time of 43.9 months (0.3-106.3). There were no differences in anastomotic biliary strictures recurrence rate, time between stent placement and recurrence, or the presence of cholangitis based on whether the BBS was deployed in one or two steps. Patients with end-to-end anastomosis had a higher anastomotic biliary strictures recurrence (or 10.8; 1.4-81.3, p=0.008) than those with bilioenteric anastomosis. The use of biodegradable stents stents could be good option for treating anastomotic biliary strictures in pediatric liver transplant patients, with our series showing a success rate of over 90% and an average follow-up of 43.9 months.

Randomized Comparison of NovelLow-Dose Sirolimus-Eluting Biodegradable Polymer Stent vsSecond-Generation DES: TARGET-IV NA Trial.

Drug-eluting stents (DESs) with controlled antiproliferative drug release reduce restenosis risk, but durable polymers can delay healing and inhibit reendothelialization. The Firehawk biodegradable polymer sirolimus-eluting stent (BP-SES) has a fully biodegradable sirolimus-containing polymer coating localized to recessed abluminal grooves on the stent surface and delivers roughly one-third the drug dose of other DESs. We report the primary results of the TARGET-IV NA (Firehawk Rapamycin Target Eluting Coronary Stent North American Trial) randomized controlled trial comparing clinical outcomes with BP-SES vs currently used second-generation DESs. The TARGET-IV NA study was a prospective, multicenter, single-blind, 1:1 randomized noninferiority trial comparing the BP-SES with control in North America and Europe among patients undergoing percutaneous coronary intervention for chronic or acute coronary syndromes. The primary endpoint was target lesion failure (TLF) at 12months (composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization). The primary analysis (intention-to-treat) tested noninferiority of BP-SES vs control using an absolute margin of 3.85% and 1-sided α of 0.025. Noninferiority-powered secondary endpoints were tested in an optical coherence tomography substudy (endpoint: mean neointimal hyperplasia thickness) and an angiography substudy (endpoint: in-stent late lumen loss). A total of 1,720 patients (mean age 66 years; 74% male) with 2,159 lesions were randomly allocated to receive either BP-SES (860 patients, 1,057 lesions) or control second-generation DES (860 patients, 1,084 lesions). Atotal of 61% of patients presented with stable coronary disease, 32% had unstable angina, and 7% had non-ST-segment elevation myocardial infarction (NSTEMI) or recent ST-segment elevation myocardial infarction. The rate of TLF with BP-SES was noninferior to control at 12months (3.4% vs 3.3%, absolute risk difference 0.13%, upper bound 97.5%CI: 2.03, Pnoninferiority< 0.0001). Cardiac death, myocardial infarction, and stent thrombosis rates were similar between groups. Angiographic follow-up was available in 104 patients (97.2% of those enrolled in the angiographic substudy) and 128 (94.1%) lesions. At 13months, the powered secondary endpoint of mean in-stent late lumen loss was 0.149 ± 0.263mm for BP-SES and 0.327 ± 0.463mm for control (least squares mean difference:-0.178; 90%CI:-0.2943 to-0.0632; Pnoninferiority< 0.0001). The optical coherence tomography substudy included 37 patients (42 lesions) with no difference in mean neointimal hyperplasia thickness between groups at 13months (Pnoninferiority=0.01). The biodegradable polymer sirolimus-eluting stent was noninferior to currently used second-generation DES with regard to TLF at 1 year. (Firehawk® Rapamycin Target Eluting Coronary Stent North American Trial; NCT04562532).

Histological and morphometrical evaluation of the urethral wall after bioresorbable stent implantation in male New Zealand White Rabbits: A preliminary study.

The aim of the study was the histological and morphometrical evaluation of the urethral wall at three time points after bioresorbable stent implantation in male New Zealand White Rabbits. The research was performed on 26 male New Zealand White rabbits aged 3-4 months and weighing 2.1-3.0 kg. Two models of bioresorbable sodium alginate-based stents were developed and implanted into the urethral lumen for one (T1), three (T3), and six weeks (T6). Sections of 5 µm thickness were cut from the urethra at intervals of 2 mm. The sliced sections were stained with hematoxylin-eosin (H&E), Van Gieson's (VG), Von Kossa, and Movat-Russell modified pentachrome (MOVAT) staining methods. The study provided valuable information for future models of urethral stents. The first model of the stent failed to fit the requirements due to inadequate mechanical properties. It curled up on itself losing the ability to adhere to the animals' urethra and was bioresorbed three weeks after implantation. The more rigid no. 2 stent was effective in widening the urethral lumen but did not biodegrade during the experiment. A comprehensive assessment of the second model's properties of biosorption and biointegration requires an extended observation of at least 12 months for an in depth morphological analysis. Stent migration is not likely to be caused solely by the mechanical properties of the urethra or urinary flow but mainly by muscle contraction of the organ wall.

TCT-424 Pathologic Analysis of Fibrin Deposition Around Stent Struts Within 1 Month After Placement of Circumferentially Coated Durable Polymer Drug-Eluting Stents and Abluminally Coated Biodegradable Polymer Drug-Eluting Stents for Acute Coronary Syndrome

TCT-424 Pathologic Analysis of Fibrin Deposition Around Stent Struts Within 1 Month After Placement of Circumferentially Coated Durable Polymer Drug-Eluting Stents and Abluminally Coated Biodegradable Polymer Drug-Eluting Stents for Acute Coronary Syndrome

TCT-394 Peripheral Bioresorbable Scaffold Made by Multi-Axial Extrusion Technology: New Material, Design, and First-in-Human Experience

TCT-394 Peripheral Bioresorbable Scaffold Made by Multi-Axial Extrusion Technology: New Material, Design, and First-in-Human Experience

TCT-367 Impact of Optical Coherence Tomography Guidance During Bioresorbable Scaffold Implantation: Decision Making and Post-Procedure Outcomes

TCT-367 Impact of Optical Coherence Tomography Guidance During Bioresorbable Scaffold Implantation: Decision Making and Post-Procedure Outcomes

TCT-370 Clinical Safety and Angiographic Performance of the Fantom Encore Bioresorbable Scaffold: Insights From an Italian Center

TCT-370 Clinical Safety and Angiographic Performance of the Fantom Encore Bioresorbable Scaffold: Insights From an Italian Center

TCT-362 Optimal Pre-Dilatation Treatment Before Implantation of a Magmaris Bioresorbable Scaffold in Coronary Artery Stenosis: The OPTIMIS Trial

TCT-362 Optimal Pre-Dilatation Treatment Before Implantation of a Magmaris Bioresorbable Scaffold in Coronary Artery Stenosis: The OPTIMIS Trial

S160 Dexamethasone-Eluting and Self-Expanding Biodegradable Stents Effectively Reduce Fibrosis in Cases of Biliary Stricture

S160 Dexamethasone-Eluting and Self-Expanding Biodegradable Stents Effectively Reduce Fibrosis in Cases of Biliary Stricture

3D-printed poly(p-dioxanone)/graphene oxide composite bioresorbable stents for congenital heart disease treatment

Bioresorbable stents (BRSs) offer significant advantages in treating congenital heart disease-related vascular stenoses, especially for pediatric patients. However, the insufficient mechanical performance of polymeric BRSs remains a critical challenge. In this study, Poly(p-dioxanone) (PPDO) was incorporated with graphene oxide (GO) for the first time to improve both mechanical properties and biocompatibility. PPDO/GO composites with varying GO contents were fabricated via solution mixing and solvent casting, and tensile tests revealed that lower GO content levels (0.2% and 0.5%) significantly improved the Young&amp;rsquo;s modulus, tensile strength, and elongation at break of PPDO due to hydrogen bonding and increased degree of crystallinity. 3D-printed PPDO/GO sliding-lock stents with optimal GO contents were fabricated by fused deposition modeling and demonstrated superior compression force compared to pristine PPDO stents. In vitro hemocompatibility and cytocompatibility assessments showed that 3D-printed PPDO/GO stents exhibited low hemolysis rate, reduced platelet adhesion, and enhanced adhesion and proliferation of endothelial cells. In vivo evaluation further demonstrated improved endothelialization in rat abdominal aortas implanted with 3D-printed PPDO/GO filaments for 4 weeks. Overall, PPDO/0.5%GO exhibited superior performance in compression force, hemocompatibility, cytocompatibility, and in vivo endothelialization. This study, for the first time, combines PPDO with GO and explains the mechanism of the enhanced mechanical properties of PPDO/GO composite material. Using 3D printing, PPDO/GO BRS with improved compression performance and biocompatibility were developed, highlighting its potential value for treating pediatric patients with CHD-related vascular stenoses.

Biodegradable internal biliary stenting in orthotopic liver transplantation – A feasibility study

IntroductionBiliary complications remain a common cause of morbidity after liver transplantation and often require invasive interventions to manage. We aimed to assess the technical feasibility and safety of placement of a biodegradable stent across the biliary anastomosis at the time of liver transplantation in patients having a duct to duct biliary reconstruction. MethodsFor this prospective, single-arm, descriptive study, 10 consecutive patients undergoing whole graft, deceased donor, liver transplantation and duct-to-duct biliary tract reconstruction were enrolled and a biodegradable biliary stent was sutured into the bile duct across the anastomosis. ResultsIn all 10 patients it was technically feasible to place and secure the stent safely during the operation. After >6 months (median of 212 days) follow up, no patients had developed biliary anastomotic stricture. One patient had transient bile leak immediately post-operative that was managed conservatively. One patient required endoscopic intervention for non-anastomotic stricture development and biliary cast material that had resulted in stent dysfunction. DiscussionThe results of this study suggest surgical feasibility of placement of an absorbable biliary stent across the biliary anastomosis at the time of liver transplantation, as well as an acceptable safety profile. Further studies are required to confirm these safety and feasibility findings and to assess efficacy in reducing rates of biliary complications and the need for endoscopic intervention in the early post-transplant period.

Recent Advancements in Drug-Eluting Stents: A Comprehensive Review

Drug-eluting stents (DES) have revolutionized the field of interventional cardiology by significantly reducing restenosis rates compared to bare-metal stents (BMS). Over the past two decades, there have been remarkable advancements in DES technology aimed at improving efficacy, safety, and long-term outcomes. This comprehensive review provides an overview of recent developments in DES design, drug formulations, coatings, and delivery systems. It discusses the clinical evidence supporting the efficacy and safety of next-generation DES and explores emerging strategies to address remaining challenges, such as late stent thrombosis and neo atherosclerosis. Additionally, the paper examines future directions in DES research, including bioresorbable stents, drug-free coatings, and personalized approaches to stent selection.

Evolution of Atomic-Level Interfacial Fracture Mechanics in Magnesium-Zinc Compounds Used for Bioresorbable Vascular Stents.

Bioresorbable magnesium-metal vascular stents are gaining popularity due to their biodegradable nature and good biological and mechanical properties. They are also suitable candidate materials for biodegradable stents. Due to the rapid degradation rate of Mg metal vascular scaffolds, a Mg/Zn bilayer composite was formed by a number of means, such as magnetron sputtering and physical vapor deposition, thus delaying the degradation time of the Mg metal vascular scaffolds while providing good radial support for the stenotic vessels. However, the interlaminar compounds at the metal interface have an essential impact on the mechanical properties of the bi-material interface, especially the cracking and delamination of the Mg matrix Zn coating vascular stent in the radially expanded process layer. Intermetallic compounds (IMCs) are commonly found in dual-layer composites, such as Mg/Zn composites and multi-layer structures. They are frequently overlooked in simulations aiming to predict mechanical properties. This paper analyses the interfacial failure processes and evolutionary mechanisms of interfacial fracture mechanics of a Mg/Zn interface with an intermetallic compound layer between coated Zn and Mg matrix metallic vascular stents. The simulation results show that the fracture mode in the Mg/Zn interface with an intermetallic compound involves typical ductile fracture under static tensile conditions. The dislocation line defects mainly occur on the side of the Mg, which induces the Mg/Zn interfacial crack to expand along the interface into the pure Mg. The stress intensity factor and the critical strain energy release rate decrease as the intermetallic compound layer's thickness gradually increases, indicating that the intensity of stress and the force of the crack extending and expanding along the crack tip are weakened. The presence of intermetallic compounds at the interface can significantly strengthen the mechanical properties of the material interface and alleviate the crack propagation between the interfaces.