This paper presents a chemo-mechano-biological framework for arterialphysiopathology. The model accounts for the fine remodelling in the multi-scale hierarchical arrangement of tissue constituents and for the diffusion of molecular species involved in cell-cell signalling pathways. Effects in terms of alterations in arterial compliance are obtained. A simple instructive example is introduced. Although oversimplified with respect to realistic case studies, the proposed application mimics the biochemical activity of matrix metallo- proteinases, transforming growth factors beta and interleukins on tissue remodelling. Effects of macrophage infiltration, of intimal thickening and of a healing phase are investigated, highlighting the corresponding influence on arterial compliance. The obtained results show that the present approach is able to capture changes in arterial mechanics as a consequence of the alterations in tissue biochemical environment and cellular activity, as well as to incorporate the protective role of both autoimmune responses and pharmacological treatments.

In this paper we consider drug binding in the arterialwall following delivery by a drug-eluting stent. Whilst it is now generally accepted that a non-linear saturable reversible binding model is required to properly describe the binding process, the precise form of the binding model varies between authors. Our particular interest in this manuscript is in assessing to what extent modelling specific and non-specific binding in the arterial wall as separate phases is important. We study this issue by extending a recently developed coupled model of drug release and arterial tissue distribution, and comparing simulated profiles of drug concentration and drug mass in each phase within the arterial tissue.

We present a method for applying a class of velocity-dependent forces within a multicomponent lattice Boltzmann equation simulation that is designed to recover continuum regime incompressible hydrodynamics. This method is applied to the problem, in two dimensions, of constraining to uniformity the tangential velocity of a vesicle membrane implemented within a recent multicomponent lattice Boltzmann simulation method, which avoids the use of Lagrangian boundary tracers. The constraint of uniform tangential velocity is carried by an additional contribution to an immersed boundary force, which we derive here from physical arguments. The result of this enhanced immersed boundary force is to apply a physically appropriate boundary condition at the interface between separated lattice fluids, defined as that region over which the phase-field varies most rapidly. Data from this enhanced vesicle boundary method are in agreement with other data obtained using related methods [e.g., T. Kruger, S. Frijters, F. Gunther, B. Kaoui, and J. Harting, Eur. Phys. J. 222, 177 (2013)] and underscore the importance of a correct vesicle membrane condition.

Nowadays, several models of unidimensional fluid jets exploit discrete element methods. In some cases, as for models aiming at describing the electrospinning nanofabrication process of polymer fibers, discrete element methods suffer a non-constant resolution of the jet representation. We develop a dynamic mesh- refinement method for the numerical study of the electro-hydrodynamic behavior of charged jets using discrete element methods. To this purpose, we import ideas and techniques from the string method originally developed in the framework of free-energy landscape simulations. The mesh-refined discrete element method is demonstrated for the case of electrospinning applications.

In this paper we present a general model of drug release from a drug delivery device and the subsequent transport in biological tissue. The model incorporates drug diffusion, dissolution and solubility in the polymer coating, coupled with diffusion, convection and reaction in the biological tissue. Each layer contains bound and free drug phases so that the resulting model is a coupled two-phase two-layer system of partial differential equations. One of the novelties is the generality of the model in each layer. Within the drug coating, our model includes diffusion as well as three different models of dissolution. We show that the model may also be used in cases where dissolution is rapid or not relevant, and additionally when drug release is not limited by its solubility. Within the biological tissue, the model can account for nonlinear saturable reversible binding, with linear reversible binding and linear irreversible binding being recovered as special cases. The generality of our model will allow the simulation of the release from a wide range of drug delivery devices encompassing many different applications. To demonstrate the efficacy of our model we simulate results for the particular application of drug release from arterial stents.

Program summary We present the open-source computer program JETSPIN, specifically designed to simulate the electro-spinning process of nanofibers. Its capabilities are shown with proper reference to the underlying model, as well as a description of the relevant input variables and associated test-case simulations. The various interactions included in the electrospinning model implemented in JETSPIN are discussed in detail. The code is designed to exploit different computational architectures, from single to parallel processor workstations. This paper provides an overview of JETSPIN, focusing primarily on its structure, parallel implementations, functionality, performance, and availability.

We investigate the effects of dissipative air drag on the dynamics of electrified jets in the initial stage of the electrospinning process. The main idea is to use a Brownian noise to model air drag effects on the uniaxial elongation of the jets. The developed numerical model is used to probe the dynamics of electrified polymer jets at different conditions of air drag force, showing that the dynamics of the charged jet is strongly biased by the presence of air drag forces. This study provides prospective beneficial implications for improving forthcoming electrospinning experiments. (C) 2015 Elsevier Ltd. All rights reserved.

We present a nonlinear Langevin model to investigate the early-stage dynamics of electrified polymer jets in electrospinning experiments. In particular, we study the effects of air drag force on the uniaxial elongation of the charged jet, right after ejection from the nozzle. Numerical simulations show that the elongation of the jet filament close to the injection point is significantly affected by the nonlinear drag exerted by the surrounding air. These results provide useful insights for the optimal design of current and future electrospinning experiments.

In this paper we present a model of drug release from a drug eluting-stent and the subsequent drug transport in the arterial wall. In order to study the complete process, a two-phase mathematical model describing the transport of a drug between two coupled media of different properties and dimensions is presented. A system of partial differential equations describes both the solid-liquid transfer (dissolution) and diffusion processes in the polymeric substrate as well as diffusion, convection and reaction in the tissue layer. We adopt a semi-analytical approach in solving the four resulting equations. The model serves as a useful tool for providing insight into the influence of solid-liquid mass transfer in drug-eluting stent systems.

A novel, coarse-grained, single-framework 'Eulerian' model for blood flow in the microvascular circulation is presented and used to estimate the variations in flow properties that accrue from all of the following: (i) wall position variation, associated with the endothelial cells' (ECs) shape, (ii) glycocalyx layer (GL) effects and (iii) the particulate nature of blood. We stress that our new model is fully coupled and uses only a single Eulerian computational framework to recover complex effects, dispensing altogether with the need for, e.g. re-meshing and advected sets of Lagrangian points. Physically, blood is modelled as a two-component, incompressible fluid - the plasma and corpuscular elements dispersed in it. The latter are modelled as deformable liquid droplets of increased viscosity. Interfacial membrane effects are present to mimic key blood properties and to avoid droplets' coalescence. The model is encapsulated within a multi-component lattice Boltzmann method that uses a sub-lattice 'wavy wall' closure to represent the ECs. Between this boundary and the flow domain, the model incorporates a coarse-grained representation of the endothelial GL, which is known to cover microvessel walls. The endothelial glycocalyx is modelled as a medium of variable and adaptive porosity, with approaching droplets being subject to a repulsive elastic force. Numerical simulations are presented to show the combined and simultaneous influence on fundamental flow properties of the EC wall undulation, the glycocalyx compression and repulsion and the particulate nature of blood. Several characteristic hemodynamical features of microvessel flow are successfully reproduced, including the deformability of particulates and the Fahraeus-Lindqvist effect. Moreover, the importance of modelling the GL is manifest in the magnitude of and the temporal variations in the flow rate and wall shear stresses.

One of the promising frontiers of bioengineering is the controlled release of a therapeutic drug from a vehicle across the skin (transdermal drug delivery). In order to study the complete process, a two-phase mathematical model describing the dynamics of a substance between two coupled media of different properties and dimensions is presented. A system of partial differential equations describes the diffusion and the binding/unbinding processes in both layers. Additional flux continuity at the interface and clearance conditions into systemic circulation are imposed. An eigenvalue problem with discontinuous coefficients is solved and an analytical solution is given in the form of an infinite series expansion. The model points out the role of the diffusion and reaction parameters, which control the complex transfer mechanism and the drug kinetics across the two layers. Drug masses are given and their dependence on the physical parameters is discussed.

We present a general model of drug release from a drug delivery device and the subsequent transport in biological tissue. The model incorporates drug diffusion, dissolution and solubility in the polymer coating, coupled with diffusion, convection and reaction in the biological tissue. Each layer contains bound and free drug phases so that the resulting model is a coupled two-phase two-layer system of partial differential equations. One of the novelties is the generality of the model in each layer. Within the drug coating, our model includes diffusion as well as three different models of dissolution. We show that the model may also be used in cases where dissolution is rapid or not relevant, and additionally when drug release is not limited by its solubility. Within the biological tissue, the model can account for nonlinear saturable reversible binding, with lin- ear reversible binding and linear irreversible binding being recovered as special cases.

Recent developments of the lattice Boltzmann method for large-scale haemodynamic applications are presented, with special focus on multiscale aspects, including the self-consistent dynamics of suspended biological bodies and their coupling to surface structures, such as the glycocalyx, in the proximity of endothelium using unstructured grids. The description of such multiscale phenomena, each one treated with a suitable variation of the lattice Boltzmann method, opens up new perspectives for a fundamental understanding of the physical mechanisms underlying cardiovascular pathologies, such as plaque growth and the subsequent development of atherosclerotic diseases.

A model of drug release from an eluting stent to the arterial wall is presented. The coating layer is described as a porous reservoir where the drug is initially loaded in a polymer-encapsulated solid phase, and is then released both to the coating and to the tissue of the arterial wall in a free phase. The wall is treated as a heterogeneous porous medium and the drug transfer through it is modeled by a non-homogeneous set of coupled partial differential equations that describe a convection-diffusion-reaction process. Change of phases due to drug dissolution in the coating and binding-unbinding reactions in the arterial wall are addressed. Numerical results show a strong coupling of the release kinetics in the polymer and the drug dynamics in the wall, and this coupling depends on the physico-chemical drug properties, the microstructure of the polymeric stent coating and the properties of the arterial wall.