Investigating the Equivalent Plastic Strain in a Variable Ring Length and Strut Width Thin-Strut Bioresorbable Scaffold.

PURPOSE: The ArterioSorb[Formula: see text] bioresorbable scaffold (BRS) developed by Arterius Ltd is about to enter first in man clinical trials. Previous generations of BRS have been vulnerable to brittle fracture, when expanded via balloon inflation in-vivo, which can be extremely detrimental to patient outcome. Therefore, this study explores the effect of variable ring length and strut width (as facilitated by the ArterioSorb[Formula: see text] design) on fracture resistance via analysis of the distribution of equivalent plastic strain in the scaffold struts post expansion. Scaffold performance is also assessed with respect to side branch access, radial strength, final deployed diameter and percentage recoil. METHODS: Finite element analysis was conducted of the crimping, expansion and radial crushing of five scaffold designs comprising different variations in ring length and strut width. The Abaqus/Explicit (DS SIMULIA) solution method was used for all simulations. Direct comparison between in-silico predictions and in-vitro measurements of the performance of the open cell variant of the ArterioSorb[Formula: see text] were made. Paths across the width of the crown apex and around the scaffold rings were defined along which the plastic strain distribution was analysed. RESULTS: The in-silico results demonstrated good predictions of final shape for the baseline scaffold design. Percentage recoil and radial strength were predicted to be, respectively, 2.8 and 1.7 times higher than the experimentally measured values, predominantly due to the limitations of the anisotropic elasto-plastic material property model used for the scaffold. Average maximum values of equivalent plastic strain were up to 2.4 times higher in the wide strut designs relative to the narrow strut scaffolds. As well as the concomitant risk of strut fracture, the wide strut designs also exhibited twisting and splaying behaviour at the crowns located on the scaffold end rings. Not only are these phenomena detrimental to the radial strength and risk of strut fracture but they also increase the likelihood of damage to the vessel wall. However, the baseline scaffold design was observed to tolerate significant over expansion without inducing excessive plastic strains, a result which is particularly encouraging, due to post-dilatation being commonplace in clinical practice. CONCLUSION: Therefore, the narrow strut designs investigated herein, are likely to offer optimal performance and potentially better patient outcomes. Further work should address the material modelling of next generation polymeric BRS to more accurately capture their mechanical behaviour. Observation of the in-vitro testing indicates that the ArterioSorb[Formula: see text] BRS can tolerate greater levels of over expansion than anticipated.

Exploring a parallel rheological framework to capture the mechanical behaviour of a thin-strut polymeric bioresorbable coronary scaffold.

Computational modelling of bioresorbable scaffolds (BRS) has employed several different material property models, ranging from those based on simple elasto-plastic theory through to anisotropic parallel network models that capture the viscoelastic-plastic behaviour observed in poly-l-lactic acid (PLLA). The increased complexity of higher fidelity material models, particularly in terms of calibration to in-vitro data, can limit their use. Consequently, their suitability for predicting the mechanical response of next-generation BRS is not well understood. Therefore, we have used the Bergstrom-Boyce (BB) parallel network material model, implemented in Abaqus/Explicit (Dassault Systemes), to investigate the mechanical response of a scaffold based upon the ArterioSorbTM BRS (Arterius Ltd, Leeds, UK). In-silico crimping, balloon expansion and radial crushing were simulated and validated against an analogous in-vitro test. Calibration of the model to uniaxial tensile test data was considered given the model's strain rate dependency and the inability to maintain the natural time period of the simulation when using the explicit solution method in finite element analysis. The isotropic limitations of this model were also explored. The model was also compared to an elasto-plastic model developed by the authors in previous work. Relative to bench-top measurements, prediction of the final diameter and radial strength of the scaffold by the BB model was found to be significantly more accurate than other models, within 2% of the in-vitro result. Additionally, the effect of the crimping strategy and an elevated ambient temperature upon the in-silico prediction of the post-crimping scaffold diameter were investigated. A multi-step crimping process with holding to facilitate stress relaxation and the lower stresses induced by the increased temperature were found to improve the accuracy of the predicted post-crimping scaffold diameter.

Investigating the material modelling of a polymeric bioresorbable scaffold via in-silico and in-vitro testing.

The accurate material modelling of poly-l-lactic acid (PLLA) is vital in conducting finite element analysis of polymeric bioresorbable scaffolds (BRS) to investigate their mechanical performance and seek improved scaffold designs. To date, a large variety of material models have been utilised, ranging from simple elasto-plastic models to high fidelity parallel network models. However, no clear consensus has been reached on the appropriateness of these different models and whether simple, less computationally expensive models can serve as acceptable approximations. Therefore, we present a study which explored the use of different isotropic and anisotropic elasto-plastic models in simulating the balloon expansion and radial crushing of the thin-strut (sub-100 µm) ArterioSorbTM BRS using the Abaqus/Explicit (DS SIMULIA) solution method. Stress-strain data was obtained via tensile tests at two different displacement rates. The use of isotropic and transversely isotropic elastic theories was explored, as well as the implementation of stress relaxation in the plastic regime of the material. The scaffold performance was quantified via its post-expansion diameter, percentage recoil and radial strength. The in-silico results were validated via comparison with in-vitro data of an analogous bench test. Accurately predicting both the post-expansion scaffold shape and radial strength was found to be challenging using the in-built Abaqus models. Therefore, a novel user-defined material model was developed via the VUMAT subroutine which improved functionality by facilitating a variable yield ratio, dependent upon the plastic strain as well as stress relaxation in overly strained elements. This achieved prediction of the radial strength within 1.1% of the in-vitro results and the scaffold's post-expansion diameter within 6.7%. A realistic multi-balloon simulation strategy was also used which confirmed that a mechanism exists in the PLLA which facilitates the extremely low percentage recoil behaviour observed in the ArterioSorbTM BRS. This could not be captured by the aforementioned material property models.

Preclinical evaluation of a thin-strut bioresorbable scaffold (ArterioSorb): acute-phase invasive imaging assessment and hemodynamic implication.

AIMS: The aim of this study was to assess the acute performance of the 95 µm ArterioSorb oriented poly L-lactic acid (PLLA) scaffold in comparison with the XIENCE metallic drug-eluting stent (DES) in porcine coronary arteries. METHODS AND RESULTS: In 15 non-atherosclerotic Yucatan mini pigs, the ArterioSorb (3.0/14 mm) and XIENCE (3.0/15 mm) were implanted in 25 and 15 vessels, respectively. Acute performance was evaluated by using quantitative coronary angiography (QCA) and optical coherence tomography (OCT). Following three-dimensional reconstruction of the coronary arteries, endothelial shear stress (ESS) was quantified using non-Newtonian steady-flow simulation. Acute recoil measured by QCA was comparable in the two arms. Post-procedural flow and scaffold/stent area by OCT did not differ between the two devices. ESS post procedure was comparable between ArterioSorb and XIENCE (2.21±1.97 vs 2.25±1.71 Pa, p=0.314). CONCLUSIONS: Acute recoil, luminal dimensions and ESS in the ArterioSorb oriented PLLA scaffold with thin struts of 95 µm were comparable to those in the XIENCE metallic DES.

Post-implantation shear stress assessment: an emerging tool for differentiation of bioresorbable scaffolds.

Optical coherence tomography based computational flow dynamic (CFD) modeling provides detailed information about the local flow behavior in stented/scaffolded vessel segments. Our aim is to investigate the in-vivo effect of strut thickness and strut protrusion on endothelial wall shear stress (ESS) distribution in ArterioSorb Absorbable Drug-Eluting Scaffold (ArterioSorb) and Absorb everolimus-eluting Bioresorbable Vascular Scaffold (Absorb) devices that struts with similar morphology (quadratic structure) but different thickness. In three animals, six coronary arteries were treated with ArterioSorb. At different six animals, six coronary arteries were treated with Absorb. Following three-dimensional(3D) reconstruction of the coronary arteries, Newtonian steady flow simulation was performed and the ESS were estimated. Mixed effects models were used to compare ESS distribution in the two devices. There were 4591 struts in the analyzed 477 cross-sections in Absorb (strut thickness = 157 µm) and 3105 struts in 429 cross-sections in ArterioSorb (strut thickness = 95 µm) for the protrusion analysis. In cross-section level analysis, there was significant difference between the scaffolds in the protrusion distances. The protrusion was higher in Absorb (97% of the strut thickness) than in ArterioSorb (88% of the strut thickness). ESS was significantly higher in ArterioSorb (1.52 ± 0.34 Pa) than in Absorb (0.73 ± 2.19 Pa) (p = 0.001). Low- and very-low ESS data were seen more often in Absorb than in ArterioSorb. ArterioSorb is associated with a more favorable ESS distribution compared to the Absorb. These differences should be attributed to different strut thickness/strut protrusion that has significant effect on shear stress distribution.

Coronary stents seeded with human trophoblastic endovascular progenitor cells show accelerated strut coverage without excessive neointimal proliferation in a porcine model.

AIMS: The success of percutaneous coronary intervention (PCI) has been limited by restenosis and stent thrombosis. Delayed or incomplete endothelial regeneration is believed to be a key factor responsible for these events. Developing a stent with an accelerated healing profile may be of benefit. We aimed to evaluate the feasibility and safety of seeding a bare metal stent (BMS) with human trophoblastic endovascular progenitor cells (hTEC) derived from human embryonic stem cells. A porcine coronary artery model was used to compare the rate and extent of endothelial regeneration and the degree of neointimal proliferation. Characterisation of hTEC confirmed a mixed progenitor and endothelial cell phenotype. The biodistribution and fate of hTEC were studied using radiolabelled 111Indium oxine and fluorescent in situ hybridisation. Scanning electron microscopy showed earlier endothelial coverage in hTEC-seeded stents as compared to similar BMS. hTEC-seeded BMS achieved complete stent coverage in three days. Quantitative coronary angiography, intravascular ultrasound assessment and histomorphometry showed no difference in neointimal hyperplasia between hTEC-seeded and control BMS. hTEC seeding of coronary stents is a novel and safe approach to accelerate endothelial regeneration without increasing neointimal proliferation.

A hydrophilic technology for intermittent urinary catheters.

A biocompatible and highly lubricous hydrophilic coating has been developed for intermittent urinary catheters. The coating has additives incorporated into it, which reduce the drying out of the catheter when it is inserted into the urethra, and antimicrobial agents can be incorporated into it to minimise the trauma associated with catheterisation.

Polymer coating techniques for drug-eluting stents.

As the use of coronary stents continues to expand worldwide, in-stent restenosis remains a major clinical problem for interventional cardiologists. However, recent clinical trials have shown that the drug-eluting stents are the most promising method for reducing the restenosis and allowing the injured vessel to heal. Further development work is focused on investigating the use of this technology with a range of drugs for the inhibition of restenosis.