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Current generation of bioresorbable coronary scaffolds (BRS) posed thrombogenicity and deployment issues owing to its thick struts and overall profile. To this end, we hypothesize that the use of nanocomposite materials is able to provide improved material properties and sufficient radial strength for the intended application even at reduced strut thickness. The nanocomposite formulations of tantalum dioxide (Ta2O5), L-lactide functionalized (LA)-Ta2O5, hydroxyapatite (HA) and LA-HA with poly-l-lactic acid (PLLA) were evaluated in this study. Results showed that tensile modulus and strength were enhanced with non-functionalized nanofillers up until 15 wt% loading, whereas ductility was compromised. On the other hand, functionalized nanofillers/PLLA exhibited improved nanofiller dispersion which resulted higher tensile modulus, strength, and ductility. Selected nanocomposite formulations were evaluated using finite element analysis (FEA) of a stent with varying strut thickness (80, 100 and 150 μm). FEA data has shown that nanocomposite BRS with thinner struts (80-100 μm) made with 15 wt% LA-Ta2O5/PLLA and 10 wt% LA-HA/PLLA have increased radial strength, stiffness and reduced recoil compared to PLLA BRS at 150 μm. The reduced strut thickness can potentially mitigate issues such as scaffold thrombosis and promote re-endothelialisation of the vessel. This work was supported by the Singapore National Health Innovation Centre (NHIC) Innovation to Develop Grant. (NHIC-I2D-1412034).

Provisional stenting is considered the gold standard approach for most bifurcation lesions, but the benefit of routine side branch (SB) strut dilatation has not been fully elucidated. A benchtop model was used to determine the benefits of routine side branch (SB) dilatation techniques on strut apposition, acute thrombogenicity, and flow disruption. Three different provisional bifurcation techniques were compared: no SB dilatation "keep it open" method (KIO), sequential balloon dilatation (SBD), and kissing balloon inflation (KBI). Stents were deployed in a silicon bifurcation model and perfused with blood at a flow rate of 200 ml/min for 60 min. Optical coherence tomography (OCT) pullbacks were obtained before and after flow perfusion to conduct strut analysis and acute thrombus measurement respectively. Computational fluid dynamics (CFD) models were created using OCT pullbacks and simulated based on experimental conditions to analyze flow disruption. The strut analysis showed that KBI had the lowest percentage of floating (10.6 ± 2.3%) (p = 0.0004) and malapposed (41.2 ± 8.5%) struts (p = 0.59), followed by SBD and then KIO. This correlated to KBI having the lowest amount of thrombus formed at the SB, followed by SBD, with KIO being the most thrombogenic (KBI: 0.84 ± 0.22mm2, SBD: 1.17 ± 0.25mm2, KIO: 1.31 ± 0.36mm2, p = 0.18). CFD models also predicted a similar trend, with KBI having the lowest amount of area of high shear rate as well as flow recirculation. Based on this benchtop model, SB intervention strategies demonstrated a reduction in number of struts and resulting thrombogenicity at the bifurcation ostia. Graphical abstract.

Provisional stenting is considered the gold standard approach for most bifurcation lesions, but the benefit of routine side branch (SB) strut dilatation has not been fully elucidated. A benchtop model was used to determine the benefits of routine side branch (SB) dilatation techniques on strut apposition, acute thrombogenicity, and flow disruption. Three different provisional bifurcation techniques were compared: no SB dilatation "keep it open" method (KIO), sequential balloon dilatation (SBD), and kissing balloon inflation (KBI). Stents were deployed in a silicon bifurcation model and perfused with blood at a flow rate of 200 ml/min for 60 min. Optical coherence tomography (OCT) pullbacks were obtained before and after flow perfusion to conduct strut analysis and acute thrombus measurement respectively. Computational fluid dynamics (CFD) models were created using OCT pullbacks and simulated based on experimental conditions to analyze flow disruption. The strut analysis showed that KBI had the lowest percentage of floating (10.6 ± 2.3%) (p = 0.0004) and malapposed (41.2 ± 8.5%) struts (p = 0.59), followed by SBD and then KIO. This correlated to KBI having the lowest amount of thrombus formed at the SB, followed by SBD, with KIO being the most thrombogenic (KBI: 0.84 ± 0.22mm

The advancement of drug-coated balloons (DCB) presents an alternative nonstent method in the percutaneous treatment of atherosclerotic lesions. While the current generation of drug-eluting stents (DES) are the device of choice, especially in coronary artery disease (CAD), DCB has potential applications in the treatment of de novo lesions, in-stent restenosis (ISR), bifurcations, and in peripheral artery disease (PAD). In terms of coronary clinical experience, DCB is used most in ISR scenarios and more data are collected to support the use of DCB in de novo lesions compared to best-in-class DES. The use of DCB in bifurcation side branch treatment has demonstrated safety, and with good angiographic and clinical outcomes, but more data from randomized trials will be required to assess its clinical value. For PAD, the clinical outcomes of DCB with and without debulking devices in diseased femoropopliteal arteries and treatment of below-the-knee (BTK) vessels with DCB are discussed. Current data demonstrated conflicting long-term safety outcomes in the use of paclitaxel devices in the femoral and/or popliteal arteries, while the role of DCB in BTK disease remains uncertain due to a lack of randomized controlled trial data. In summary, this review provides an overall view of current DCB technologies and progress, followed by an update on DCB clinical data in the treatment of CAD and PAD.

Interventions in bifurcation lesions often requires aggressive overexpansion of stent diameter in the setting of long tapering vessel segment. Overhanging struts in front of the side branch (SB) ostium are thought to act as a focal point for thrombi formation and consequently possible stent thrombosis. This study aimed to evaluate the overexpansion capabilities and thrombogenicity at the SB ostia after implantation of four latest generation drug-eluting stents (DES) in an in-vitro bifurcation model. Four clinically available modern DES were utilized: one bifurcation dedicated DES (Bioss LIM C) and three conventional DES (Ultimaster, Xience Sierra, Biomime). All devices were implanted in bifurcation models with proximal optimization ensuring expansion before perfusing with porcine blood. Optical coherence tomography (OCT), immunofluorescence (IF) and scanning electron microscope analysis were done to determine thrombogenicity and polymer coating integrity at the over-expanded part of the stents. Computational fluid dynamics (CFD) was performed to study the flow disruption. OCT (p = 0.113) and IF analysis (p = 0.007) demonstrated lowest thrombus area at SB ostia in bifurcation dedicated DES with favorable biomechanical properties compared to conventional DES. The bifurcated DES also resulted in reduced area of high shear rate and maximum shear rate in the CFD analysis. This study demonstrated numerical differences in terms of mechanical properties and acute thrombogenicity at SB ostia between tested devices.

BACKGROUND:Attenuation-compensated (AC) technique was recently introduced to improve the plaque characterization of optical coherence tomography (OCT). Histological validation demonstrated promising results but the efficacy and reproducibility of this technique for assessing in-vivo tissue composition remains unclear.Methods and Results:OCT images portraying native (n=200) and stented (n=200) segments and 31 histological cross-sections were analyzed. AC-OCT appeared superior to conventional (C)-OCT in detecting the external elastic lamina (EEM) borders (76% vs. 65.5%); AC-OCT enabled larger EEM arc detection compared with C-OCT (174.2±58.7° vs. 137.5±57.9°; P

Aims: The aim of this study was to assess whether the culotte technique could be improved by an additional kissing dilation prior to main branch (MB) stenting. Methods and results: Double-kissing (DK) culotte was compared to the culotte and DK-crush techniques in a bench model (n=24). Results were evaluated for stent apposition, luminal opening and flow dynamics. The total procedure duration of DK-culotte was 18.3±3.4 minutes, significantly lower than for DK-crush (24.3±5.7 min; p=0.015), but similar to culotte (21.6±5.9 min, p=0.104). In DK-culotte the overall rate of moderate (200-500 μm) and significant (>500 μm) malapposition was 2.1±1.9% and 0.4±0.2%, similar as compared to culotte (3.7±3.8%, p=0.459 and 1.0±1.0%, p=0.517, respectively), and lower as compared to DK-crush (8.1±2.5%, p

Background Percutaneous coronary interventions on complex bifurcation lesions may require implantation of two stents to appropriately treat diffuse side-branch (SB) disease. Comparisons among different bifurcation stenting techniques are continuously attempted by various study designs (bench tests, computer simulations, clinical studies). Among different techniques, double kissing crush (DKC) represents the last evolution for “crushing” while T and small Protrusion (TAP) represents the evolution of “T stenting”. Both techniques are actually gaining popularity, but head-to-head comparisons are lacking. Methods and results Two last generation drug-eluting stents (Synergy™, Boston Scientific, MA, USA and Ultimaster™,Terumo Corp., Japan) were implanted in left main bifurcation bench models using TAP (n = 6 sets) and DKC (n = 6 sets) techniques. A peristaltic pump with fresh porcine blood was used to perfuse the blood through the silicone model at a flow rate of 200 ml/min for 4 min. Optical coherence tomography (OCT) was used to assess stent struts geometry and thrombus formation . SB cross sectional area as well as SB obstruction did not significantly differ between the two techniques. Numerical (but not statistically significant) differences were found in terms of malapposed struts (fewer with TAP) and floating struts (fewer with DKC). Thrombus formation after blood perfusion was similar between TAP and DKC technique (1.53 ± 1.12 vs. 1.20 ± 1.01 mm 2, p = 0.6). Conclusion The result of the present in-vitro study shows the absence of significant difference between TAP and DKC in terms of stent struts apposition and acute thrombus formation potential. Despite the completely different technical steps required, both techniques have similar performance according to such articulated pre-clinical evaluation. What is already known about this subject? Due to its limited complexity, T and Protrusion (TAP) technique is considered the to-go technique for bifurcation lesions with good long-term results. Recently, double kissing crush (DKC) technique has been gaining popularity and demonstrated promising results in randomized clinical trials. What does this study add? This in-vitro bench test study provides a unique detailed OCT comparison and local hemodynamic environment analysis of the two techniques. How might this impact on clinical practice? New insights of acute thrombogenicity and computational flow model simulation may guide percutaneous therapeutic strategies of bifurcation lesions.

Supplemental material, Supplemental_Material_final for Drug-coated balloons: Technical and clinical progress by Huiying Ang, Tobias R Koppara, Salvatore Cassese, Jaryl Ng, Michael Joner and Nicolas Foin in Vascular Medicine

Local hemodynamic forces are well-known to modulate atherosclerotic evolution, which remains one of the largest cause of death worldwide. Percutaneous coronary interventions with stent implantation restores blood flow to the downstream myocardium and is only limited by stent failure caused by restenosis, stent thrombosis, or neoatherosclerosis. Cumulative evidence has shown that local hemodynamic forces affect restenosis and the platelet activation process, modulating the pathophysiological mechanisms that lead to stent failure. This article first covers the pathophysiological mechanisms through which wall shear stress regulates arterial disease formation/neointima proliferation and the role of shear rate on stent thrombosis. Subsequently, the article reviews the current evidence on (1) the implications of stent design on the local hemodynamic forces, and (2) how stent/scaffold expansion can influence local flow, thereby affecting the risk of adverse events.

The first generation of bioresorbable stents or scaffolds (BRS) have significantly larger strut thickness compared with metallic drug-eluting stents (DES). This results in more flow disturbance, thus potentially increases scaffold thrombogenicity. Stent or scaffold thrombosis (ST) remains a major

Modern implantable medical devices have evolved beyond serving as physical surrogates, to also playing an active role in restoring bodily functions. The progress of implantable medical devices is the culmination of advances in various scientific fields such as material science, microelectronics and biomaterials. The use of polymers in biomedical applications is highly attractive, especially in soft tissue applications as polymers have the potential to elicit appropriate host tissue response. However, homopolymers often do not encompass all the desired characteristics such as mechanical properties, degradability, biocompatibility or bio-functionality. The concepts of polymer blending or polymer composites were introduced to overcome the inadequacies when using a single polymer in cardiovascular applications. Through polymer blending, polymer scaffolds made up of two or more polymers can yield scaffold stiffness closer to the human myocardium and improved hydrophilicity for better cell interaction and improved biodegradability. Polymer composites, which utilizes to reinforce the base polymer, have demonstrated improved the compliance of the vascular graft similar to human native vessels. This review presents an overview of fabrication techniques and novel applications of polymer blends and polymer composites in cardiovascular implants, ranging from coronary stents to tissue engineered constructs.

AIMS Previous studies have associated issues such as incomplete stent apposition with delayed healing and adverse events (stent thrombosis). The aim of this study was to evaluate the impact of strut apposition and stent type on the progression of stent strut coverage. METHODS AND RESULTS We evaluated in vivo in porcine models the follow-up response and coverage characteristics of well-apposed and malapposed segments of drug-eluting stents (DES) (CYPHER, PROMUS Element and Orsiro) and the Absorb bioresorbable vascular scaffold (BVS) by optical coherence tomography (OCT) sequentially, at baseline, and at one week and four weeks of follow-up. Supporting results were provided by histological analysis performed at four-week follow-up and computer simulation describing the shear characteristics around apposed and non-apposed struts. A total of 325 cross-sections containing 3,166 struts were analysed. The extent of malapposition decreased over time as a result of neointimal healing (from 7.1% at baseline to 0% at four weeks; p=0.03). At one week, 13.6% of struts in well-apposed segments were still uncovered versus 19.2% of struts in malapposed cross-sections and 77.8% of NASB struts (p

The use of bioresorbable stents (BRS) was envisioned as the fourth revolution in interventional cardiology due to its potential benefits such as restoration of vasomotion and elimination of late adverse event after stent degradation. However, the clinical outcomes of Abbott's Vascular polymer-based Bioresorbable Vascular Scaffold (BVS) have demonstrated a higher rate of scaffold thrombosis, casting uncertainties over long-term use of the device. This has encouraged the development of bioresorbable stents fabricated from resorbable metals such as magnesium-, zinc- and iron-based alloys, with the promise of improved mechanical strength and biocompatibility. The review is categorised into the three main sections, namely: Fundamentals of resorbable metals, Benchtop and preclinical evaluation of the resorbable metals and Clinical progress of a magnesium-based BRS. The alloying and metallurgical processes were discussed to understand how they affect the mechanical and corrosion behavior of resorbable metals (magnesium-, zinc- and iron-based alloys). Key results from various in vitro and preclinical studies were discussed to provide insights on their potential as BRS candidates in terms of biocompatibility and degradation profile. Lastly, results from the magnesium-based BRS (Magmaris, CE-marked) summarized the current status of research in human clinical trials.

The use of bioresorbable stents in interventional cardiology presents a novel approach in the treatment of coronary artery disease. The bioresorbable technology was introduced to overcome limitations of current metallic drug-eluting stents such as late in-stent restenosis and permanently caging the vessel. The concept of a bioresorbable stent is to provide temporal support to the vessel before being degraded and resorbed by the body, promoting vessel healing and restoration of vasomotion. Although the bioresorbable stents have many promising advantages over metallic stents, drawbacks such as insufficient radial strength of the bioresorbable material and large strut profile of the stent need to be addressed in order to enhance the performance of the bioresorbable stents. Currently, there are several bioresorbable scaffolds that are under development with some already commercially available. In this chapter, the concept of bioresorbable stents together with its advantages and limitations will be examined. An overview of the current bioresorbable platforms which include bioresorbable scaffolds made from polymers and biodegradable metallic stents will also be discussed.

AIMS The aim of this report was to examine the effect of underexpansion on stent thrombogenicity with an in vitro perfusion model. METHODS AND RESULTS Drug-eluting stent (DES) samples were partially underdeployed in silicone tubes and perfused with porcine blood containing 10% anticoagulant citrate dextrose solution for four minutes at a flow rate of 200 ml/min. Thrombus formation was evaluated and compared between the well-apposed and malapposed sections. The malapposed sections showed significantly more thrombus formation compared to the well-apposed sections (13.9 vs. 0.41 mm2, p

Aims: The aim of the study was to investigate long-term changes in lumen eccentricity and asymmetry at five years after implantation of the Absorb bioresorbable vascular scaffold (BVS). Methods and results: Out of 101 patients from the ABSORB cohort B trial, 28 patients (29 lesions) with serial optical coherence tomography (OCT) examination at four different time points (cohort B1: postprocedure, six months, two, and five years [n=13]; cohort B2: post-procedure, one, three, and five years [n=16]) were evaluated. The longitudinal variance in lumen diameter was assessed by asymmetry index (AI). An asymmetric lesion was defined as AI >0.3. The circularity of the lumen or scaffold was evaluated by the eccentricity index calculated as minimal divided by maximal luminal or scaffold diameter per cross-section. The lowest lumen eccentricity index within a scaffold segment (EIL)

Aims: The current study aimed to assess the difference in lumen dimension measurements between optical coherence tomography (OCT) and quantitative coronary angiography (QCA) in the polymeric bioresorbable scaffold and metallic stent. Methods and results: In the randomised ABSORB Japan trial, 87 lesions in the Absorb arm and 44 lesions in the XIENCE arm were analysed. Post-procedural OCT-QCA lumen dimensions were assessed in matched proximal/distal non-stented/non-scaffolded reference (n=199), scaffolded (n=145) and stented (n=75) cross-sections at the two device edges using the Bland-Altman method. In the non-stented/nonscaffolded reference segments, QCA systematically underestimated lumen diameter (LD) compared with OCT (accuracy,-0.26 mm; precision, 0.47 mm; 95% limits of agreement as a mean bias±1.96 standard deviation,-1.18-0.66 mm). When compared to OCT, QCA of the Absorb led to a more severe underestimation of the LD (-0.30 mm; 0.39 mm;-1.06-0.46 mm) than with the XIENCE (-0.14 mm; 0.31 mm;-0.75-0.46 mm). QCA underestimated LD by 9.1%, 4.9%, and 9.8% in the reference, stented, and scaffolded segments, respectively. The protrusion distance of struts was larger in the Absorb arm than in the XIENCE arm (135±27 μm vs. 18±26 μm, p

Background— The long-term fate of Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, CA) struts jailing side branch ostia has not been clarified. We therefore evaluate serially (post-procedure and at 6 months, 1, 2, 3, and 5 years) the appearance and fate of jailed Absorb bioresorbable vascular scaffold struts. Methods and Results— We performed 3-dimensional optical coherence tomographic analysis of the ABSORB Cohort B trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) up to 5 years using a novel, validated cut-plane analysis method. We included 29 patients with a total of 85 side branch ostia. From the 12 ostia which could be assessed in true serial fashion, 7 showed a pattern of initial decrease in the ostial area free from struts, followed by an increase in strut-free ostial area toward the end of the 5 years of follow-up. In a repeated-measures analysis with time as fixed variable and ostial area free from struts as dependent variable, we showed a numeric decrease in the estimated ostial area free from struts from 0.75 mm 2 (baseline) to 0.68 mm 2 (first follow-up visit at 6 months or 1 year) and 0.63 mm 2 (second follow-up visit at 2 or 3 years). However, from the second visit to the 5-year follow-up visit, there was a statistically significant increase from 0.63 to 0.89 mm 2 ( P =0.001). Struts overlying an ostium divided the ostium into compartments, and the number of these compartments decreased over time. Conclusions— This study showed that in most cases, the side branch ostial area free from struts initially decreased. However, with full scaffold bioresorption, the ostial area free from scaffold increased between 2 to 3 years and 5 years in the vast majority of patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00856856.

Crush technique has been shown to provide full scaffolding of the side branch (SB) ostium but at the expense of greater strut malapposition and higher target lesion revascularization compared to TAP technique. Recent clinical data have supported the advantages of the double kissing (DK) crush

With one-third of patients having osteoarthritis predominantly in one compartment of the knee, unicompartmental knee spacers have been introduced as a less invasive alternative to total knee replacement. However, patients with the knee spacer implanted were seen to have persistent pain, resulting in high revision rates. A static computational finite element model of the knee at full extension and 90° flexion, mimicking the peak tibio-femoral force at heel strike during gait and peak joint forces during an ascending motion from a squatting position was used to study the tibio-femoral contact pressure of different designs and proper-ties of the knee spacer. Three designs (contoured - conventional, flat and Cshaped) of the knee spacers were created and simulated with three different materials (cobalt-chromium, UHMWPE and polyurethane). The average contact pressures acting at the medial compartment of the femoral condyle were extracted for analysis. Spacers made out of soft material exerted lesser contact pressure onto the femur cartilage. In the full extension model, using a soft material of polyurethane, the C-shaped spacer exhibited the lowest femoral cartilage contact pressure with a 31% and 18% decrease from the flat and contoured spacers respectively. In the 90° knee flexion model, the contoured spacer had the lowest contact pressure among the other spacers. Contoured spacers made of polyurethane exhibited a 13% and 20% decrease from the flat and C-shaped spacers respectively. Therefore, it is suggested that the knee spacers should be made out of a softer material that can withstand the joint forces in various motions and have a geometry that would increase the contact area of the between the joints.

Background Previously, we examined the difference in stent designs across different sizes for six widely used Drug Eluting Stents (DESs). Although stent post-dilatation to larger diameter is commonly done, typically in the setting of long tapering segment or left-main PCI, there is an increasing recognition that information with regard to the different stent model designs has a critical impact on overexpansion results. This study aims to provide an update on stent model designs for contemporary DES platforms as well as test overexpansion results under with oversized post-dilatation. Methods and results We studied 6 different contemporary commercially available DES platforms: Synergy, Xience Xpedition, Ultimaster, Orsiro, Resolute Onyx and Biomatrix Alpha . We investigated for each platform the difference in stent designs across different sizes and results obtained after post-expansion with larger balloon sizes. The stents were deployed at nominal diameter and subsequently over expanded using increasingly large post dilatation balloon sizes (4.0, 5.0 and 6.0mm at 14ATM). Light microscopy was used to measure the changes in stent geometry and lumen diameter after over-expansion. For each respective DES platform, the MLD observed after overexpansion of the largest stent size available with a 6.0mm balloon was 5.7mm for Synergy , 5.6mm for Xience , 5.2mm for Orsiro , 5.8mm for Ultimaster , 5.5mm for 4mm Onyx (5.9mm for the 5mm XL size) and 5.8mm for BioMatrix Chroma. Conclusion This update presents valuable novel insights that may be helpful for careful selection of stent size for contemporary DES based on model designs. Such information is especially critical in left main bifurcation stenosis treatment where overexpansion to larger oversized diameter may be required to ensure full stent apposition.