Endothelial shear stress 5 years after implantation of a coronary bioresorbable scaffold

Aims: As a sine qua non for arterial wall physiology, local hemodynamic forces such as endothelial shear stress (ESS) may influence long-term vessel changes as bioabsorbable scaffolds dissolve. The aim of this study was to perform serial computational fluid dynamic (CFD) simulations to examine immediate and long-term haemodynamic and vascular changes following bioresorbable scaffold placement. Methods and results: Coronary arterial models with long-term serial assessment (baseline and 5 years) were reconstructed through fusion of intravascular optical coherence tomography and angiography. Pulsatile non-Newtonian CFD simulations were performed to calculate the ESS and relative blood viscosity. Time-averaged, systolic, and diastolic results were compared between follow-ups. Seven patients (seven lesions) were included in this analysis. A marked heterogeneity in ESS and localised regions of high blood viscosity were observed post-implantation. Percent vessel area exposed to low averaged ESS (7 Pa) did not significantly change (moderate ESS: 76.93% vs. 80.7%, P = 0.546; high ESS: 7.15% vs. 14.31%, P = 0.281), leading to higher ESS at follow-up. A positive correlation was observed between baseline ESS and change in lumen area at 5 years (P < 0.0001). Maximum blood viscosity significantly decreased over 5 years (4.30 ± 1.54 vs. 3.21± 0.57, P = 0.028). Conclusion: Immediately after scaffold implantation, coronary arteries demonstrate an alternans of extremely low and high ESS values and localized areas of high blood viscosity. These initial local haemodynamic disturbances may trigger fibrin deposition and thrombosis. Also, low ESS can promote neointimal hyperplasia, but may also contribute to appropriate scaffold healing with normalisation of ESS and reduction in peak blood viscosity by 5 years

Endothelial shear stress 5 years after implantation of a coronary bioresorbable scaffold

Aims As a sine qua non for arterial wall physiology, local hemodynamic forces such as endothelial shear stress (ESS) may influence long-term vessel changes as bioabsorbable scaffolds dissolve. The aim of this study was to perform serial computational fluid dynamic (CFD) simulations to examine immediate and long-term haemodynamic and vascular changes following bioresorbable scaffold placement. Methods and results Coronary arterial models with long-term serial assessment (baseline and 5 years) were reconstructed through fusion of intravascular optical coherence tomography and angiography. Pulsatile non-Newtonian CFD simulations were performed to ca

NUCLÉATION EN PRÉSENCE DE CHAMPS EXTERNES: Application aux principes actifs pharmaceutiques

In the field of pharmaceutical chemistry the crystallization of the active ingredient or intermediate is an important stage, it is going to control the physico-chemical properties of the solid obtained. The first stage of the crystallization, the nucleation, can be slow, difficult or disturbed by the appearance of another unwanted phase, solid or liquid. The obtaining of the first crystal and the research for new polymorphs need long and expensive studies. Our aim is to rationalise these researches on crystallization conditions, for that we propose, in this PhD thesis, the study and the development of new crystallization techniques on small volumes (from nL to mL) under an external field. As external fields we mean under an electric field, a light or ultrasounds irradiation. We will be able to enhance nucleation. We want to control spatial and temporal localisation of the nucleation event in metastable solutions, in order to observe and better understand the mechanism of the first nucleus appearing.Dans le domaine de la chimie pharmaceutique la cristallisation des principes actifs ou intermédiaires est une étape importante, c'est elle qui va contrôler les propriétés physico-chimiques du solide obtenu. La première étape de la cristallisation, la nucléation, peut être lente, difficile ou perturbée par l'apparition d'une autre phase, solide ou liquide, indésirable. L'obtention du premier cristal et la recherche de nouveaux polymorphes nécessitent de longues et onéreuses études. Avec pour objectif de rationaliser ces recherches de conditions de cristallisation nous proposons, dans le cadre de cette thèse, l'étude et le développement de nouvelles techniques de cristallisation sur de faibles volumes (du µL au mL) en présence d'un champ externe. Par champ externe, on entend en présence d'un champ électrique, d'un faisceau lumineux ou d'ultrasons. Il s'agira d'être capable de provoquer la nucléation de manière localisée dans le temps et l'espace au sein de solutions métastables, afin de pouvoir l'observer et de mieux comprendre le mécanisme d'apparition du premier cristal

Gel-mediated electrospray assembly of silica supraparticles for sustained drug delivery

Supraparticles (SPs) composed of smaller colloidal particles provide a platform for the long-term, controlled release of therapeutics in biomedical applications. However, current synthesis methods used to achieve high drug loading and those involving biocompatible materials are often tedious and low throughput, thereby limiting the translation of SPs to diverse applications. Herein, we present a simple, effective, and automatable alginate-mediated electrospray technique for the assembly of robust spherical silica SPs (Si-SPs) for long-term (>4 months) drug delivery. The Si-SPs are composed of either porous or nonporous primary Si particles within a decomposable alginate matrix. The size and shape of the Si-SPs can be tailored by controlling the concentrations of alginate and silica primary particles used and key electrospraying parameters, such as flow rate, voltage, and collector distance. Furthermore, the performance (including drug loading kinetics, loading capacity, loading efficiency, and drug release) of the Si-SPs can be tuned by changing the porosity of the primary particles and through the retention or removal (via calcination) of the alginate matrix. The structure and morphology of the Si-SPs were characterized by electron microscopy, dynamic light scattering, N2 adsorption-desorption analysis, and X-ray photoelectron spectroscopy. The cytotoxicity and degradability of the Si-SPs were also examined. Drug loading kinetics and loading capacity for six different types of Si-SPs, using a model protein drug (fluorescently labeled lysozyme), demonstrate that Si-SPs prepared from primary silica particles with large pores can load significant amounts of lysozyme (∼10 μg per SP) and exhibit sustained, long-term release of more than 150 days. Our experiments show that Si-SPs can be produced through a gel-mediated electrospray technique that is robust and automatable (important for clinical translation and commercialization) and that they present a promising platform for long-term drug delivery

Non-Newtonian Endothelial Shear Stress Simulation: Does It Matter?

Patient-specific coronary endothelial shear stress (ESS) calculations using Newtonian and non-Newtonian rheological models were performed to assess whether the common assumption of Newtonian blood behavior offers similar results to a more realistic but computationally expensive non-Newtonian model. 16 coronary arteries (from 16 patients) were reconstructed from optical coherence tomographic (OCT) imaging. Pulsatile CFD simulations using Newtonian and the Quemada non-Newtonian model were performed. Endothelial shear stress (ESS) and other indices were compared. Exploratory indices including local blood viscosity (LBV) were calculated from non-Newtonian simulation data. Compared to the Newtonian results, the non-Newtonian model estimates significantly higher time-averaged ESS (1.69 (IQR 1.36)Pa versus 1.28 (1.16)Pa, p < 0.001) and ESS gradient (0.90 (1.20)Pa/mm versus 0.74 (1.03)Pa/mm, p < 0.001) throughout the cardiac cycle, under-estimating the low ESS (<1Pa) area (37.20 +/- 13.57% versus 50.43 +/- 14.16%, 95% CI 11.28-15.18, p < 0.001). Similar results were also found in the idealized artery simulations with non-Newtonian median ESS being higher than the Newtonian median ESS (healthy segments: 0.8238Pa versus 0.6618Pa, p < 0.001 proximal; 0.8179Pa versus 0.6610Pa, p < 0.001 distal; stenotic segments: 0.8196Pa versus 0.6611Pa, p < 0.001 proximal; 0.2546Pa versus 0.2245Pa, p < 0.001 distal) On average, the non-Newtonian model has a LBV of 1.45 times above the Newtonian model with an average peak LBV of 40-fold. Non-Newtonian blood model estimates higher quantitative ESS values than the Newtonian model. Incorporation of non-Newtonian blood behavior may improve the accuracy of ESS measurements. The non-Newtonian model also allows calculation of exploratory viscosity-based hemodynamic indices, such as local blood viscosity, which may offer additional information to detect underlying atherosclerosis.Radiolog