In-Flow dynamics of an area-difference-energy spring-particle red blood cell model on non-uniform grids.

In this paper the area-difference-energy spring-particle (ADE-SP) red blood cell (RBC) structural model developed by Chen and Boyle is coupled with a lattice Boltzmann flux solver to simulate RBC dynamics. The novel ADE-SP model accounts for bending resistance due to the membrane area difference of RBCs while the lattice Boltzmann flux solver offers reduced computational runtimes through GPU parallelisation and enabling the employment of non-uniform meshes. This coupled model is used to simulate RBC dynamics and predictions are compared with existing experimental measurements. The simulations successfully predict tumbling, tank-treading, swinging and intermittent behaviour of an RBC in shear flow, and demonstrate the capability of the model in capturing in-flow RBC behaviours.

An Enhanced Spring-Particle Model for Red Blood Cell Structural Mechanics: Application to the Stomatocyte-Discocyte-Echinocyte Transformation.

Red blood cells (RBCs) are the most abundant cellular element suspended in blood. Together with the usual biconcave-shaped RBCs, i.e., discocytes, unusual-shaped RBCs are also observed under physiological and experimental conditions, e.g., stomatocytes and echinocytes. Stomatocytes and echinocytes are formed from discocytes and in addition can revert back to being discocytes; this shape change is known as the stomatocyte-discocyte-echinocyte (SDE) transformation. To-date, limited research has been conducted on the numerical prediction of the full SDE transformation. Spring-particle RBC (SP-RBC) models are commonly used to numerically predict RBC mechanics and rheology. However, these models are incapable of predicting the full SDE transformation because the typically employed bending model always leads to numerical instability with severely deformed shapes. In this work, an enhanced SP-RBC model is proposed in order to extend the capability of this model type and so that the full SDE transformation can be reproduced. This is achieved through the leveraging of an advanced bending model. Transformed vesicle and RBC shapes are predicted for a range of reduced volume and reduced membrane area difference (MAD), and very good agreement is obtained in the comparison of predicted shapes with experimental observations. Through these predictions, vesicle and SDE transformation phase diagrams are developed and, importantly, in the SDE case, shape boundaries are proposed for the first time relating RBC shape categories to RBC reduced volume and reduced MAD.

Oxygen Mass Transport in Stented Coronary Arteries.

Oxygen deficiency, known as hypoxia, in arterial walls has been linked to increased intimal hyperplasia, which is the main adverse biological process causing in-stent restenosis. Stent implantation has significant effects on the oxygen transport into the arterial wall. Elucidating these effects is critical to optimizing future stent designs. In this study the most advanced oxygen transport model developed to date was assessed in two test cases and used to compare three coronary stent designs. Additionally, the predicted results from four simplified blood oxygen transport models are compared in the two test cases. The advanced model showed good agreement with experimental measurements within the mass-transfer boundary layer and at the luminal surface; however, more work is needed in predicting the oxygen transport within the arterial wall. Simplifying the oxygen transport model within the blood flow produces significant errors in predicting the oxygen transport in arteries. This study can be used as a guide for all future numerical studies in this area and the advanced model could provide a powerful tool in aiding design of stents and other cardiovascular devices.

Investigation of membrane mechanics using spring networks: application to red-blood-cell modelling.

In recent years a number of red-blood-cell (RBC) models have been proposed using spring networks to represent the RBC membrane. Some results predicted by these models agree well with experimental measurements. However, the suitability of these membrane models has been questioned. The RBC membrane, like a continuum membrane, is mechanically isotropic throughout its surface, but the mechanical properties of a spring network vary on the network surface and change with deformation. In this work spring-network mechanics are investigated in large deformation for the first time via an assessment of the effect of network parameters, i.e. network mesh, spring type and surface constraint. It is found that a spring network is conditionally equivalent to a continuum membrane. In addition, spring networks are employed for RBC modelling to replicate the optical tweezers test. It is found that a spring network is sufficient for modelling the RBC membrane but strain-hardening springs are required. Moreover, the deformation profile of a spring network is presented for the first time via the degree of shear. It is found that spring-network deformation approaches continuous as the mesh density increases.

Computational fluid dynamics analysis of balloon-expandable coronary stents: influence of stent and vessel deformation.

In many computational fluid dynamics (CFD) studies of stented vessel haemodynamics, the geometry of the stented vessel is described using non-deformed (NDF) geometrical models. These NDF models neglect complex physical features, such as stent and vessel deformation, which may have a major impact on the haemodynamic environment in stented coronary arteries. In this study, CFD analyses were carried out to simulate pulsatile flow conditions in both NDF and realistically-deformed (RDF) models of three stented coronary arteries. While the NDF models were completely idealised, the RDF models were obtained from nonlinear structural analyses and accounted for both stent and vessel deformation. Following the completion of the CFD analyses, major differences were observed in the time-averaged wall shear stress (TAWSS), time-averaged wall shear stress gradient (TAWSSG) and oscillatory shear index (OSI) distributions predicted on the luminal surface of the artery for the NDF and RDF models. Specifically, the inclusion of stent and vessel deformation in the CFD analyses resulted in a 32%, 30% and 31% increase in the area-weighted mean TAWSS, a 3%, 7% and 16% increase in the area-weighted mean TAWSSG and a 21%, 13% and 21% decrease in the area-weighted mean OSI for Stents A, B and C, respectively. These results suggest that stent and vessel deformation are likely to have a major impact on the haemodynamic environment in stented coronary arteries. In light of this observation, it is recommended that these features are considered in future CFD studies of stented vessel haemodynamics.

Computational structural modelling of coronary stent deployment: a review.

The finite element (FE) method is a powerful investigative tool in the field of biomedical engineering, particularly in the analysis of medical devices such as coronary stents whose performance is extremely difficult to evaluate in vivo. In recent years, a number of FE studies have been carried out to simulate the deployment of coronary stents, and the results of these studies have been utilised to assess and optimise the performance of these devices. The aim of this paper is to provide a thorough review of the state-of-the-art research in this area, discussing the aims, methods and conclusions drawn from a number of significant studies. It is intended that this paper will provide a valuable reference for future research in this area.

Drug-eluting stents for coronary artery disease: a review.

Over the past decade the introduction of drug-eluting stents (DESs) has revolutionised the treatment of coronary artery disease. However, in recent years concern has arisen over the long-term safety and efficacy of DESs due to the occurrence of late adverse clinical events such as stent thrombosis. With this concern in mind, research and development is currently centred on increasing the long-term safety and efficacy of DESs. The aim of this paper is to provide a thorough review of currently approved and promising investigational DESs. With dozens of companies involved in the development of new and innovative anti-restenotic agents, polymeric coatings and stent platforms, it is intended that this review paper will provide a clear indication of how DESs are currently evolving and prove a valuable reference tool for future research in this area.

A full-range, multi-variable, CFD-based methodology to identify abnormal near-wall hemodynamics in a stented coronary artery.

The benefit of coronary stent implantation is reduced by excessive intimal hyperplasia which re-narrows the artery and the prevention of which is still a primary concern for clinicians. Abnormal hemodynamics create non-physiological viscous stress on the artery wall, one of the root causes of intimal hyperplasia following stent implantation. A methodology to comprehensively evaluate the viscous stress on the artery wall following stent implantation would be useful to evaluate a stent's hemodynamic performance.The proposed methodology employs 3D computational fluid dynamics, the variables wall shear stress (WSS), WSS gradient (WSSG), WSS angle gradient (WSSAG) and a statistical analysis to evaluate the viscous stress. The methodology is demonstrated and compared to a commonly used "threshold technique" for evaluating a stent's hemodynamic performance.It is demonstrated that the threshold technique is not adequate to fully analyse the viscous stress on the artery wall and can even be misleading. Furthermore, all three of the aforementioned variables should be considered as each provides a different perspective on the abnormalities that can arise in the arterial viscous stress.The hemodynamic performance of a stent can be assessed more comprehensively than with previously used methods by examining the arterial viscous stresses using the proposed methodology.