A particle-based model for endothelial cell migration under flow conditions

Endothelial cells (ECs) play a major role in the healing process following angioplasty to inhibit excessive neointima. This makes the process of EC healing after injury, in particular EC migration in a stented vessel, important for recovery of normal vessel function. In that context, we present a novel particle-based model of EC migration and validate it against in vitro experimental data. We have developed a particle-based model of EC migration under flow conditions in an in vitro vessel with obstacles. Cell movement in the model is a combination of random walks and directed movement along the local flow velocity vector. For model calibration, a set of experimental data for cell migration in a similarly shaped channel has been used. We have calibrated the model for a baseline case of a channel with no obstacles and then applied it to the case of a channel with ridges on the bottom surface, representative of stent strut geometry. We were able to closely reproduce the cell migration speed and angular distribution of their movement relative to the flow direction reported in vitro. The model also reproduces qualitative aspects of EC migration, such as entrapment of cells downstream from the flow-disturbing ridge. The model has the potential, after more extensive in vitro validation, to study the effect of variation in strut spacing and shape, through modification of the local flow, on EC migration. The results of this study support the hypothesis that EC migration is strongly affected by the direction and magnitude of local wall shear stress

Haemodynamic flow conditions at the initiation of high-shear platelet aggregation: a combined in vitro and cellular in silico study

The influence of the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compared with in vitro platelet aggregation experiments performed with porcine whole blood (WB) and platelet-rich-plasma (PRP). We studied whether the cell-depleted layer in combination with high shear and high platelet flux can account for the distribution of platelet aggregates. High platelet fluxes at the wall were found in silico. In WB, the platelet flux was about twice as high as in PRP. Additionally, initial platelet aggregation and occlusion were observed in vitro in the stenotic region. In PRP, the position of the occlusive thrombus was located more downstream than in WB. Furthermore, the shear rates and stresses in cell-based and continuum simulations were studied. We found that a continuum simulation is a good approximation for PRP. For WB, it cannot predict the correct values near the wall

Identifying the start of a platelet aggregate by the shear rate and the cell-depleted layer

Computer simulations were performed to study the transport of red blood cells and platelets in high shear flows, mimicking earlier published in vitro experiments in microfluidic devices with high affinity for platelet aggregate formation. The goal is to understand and predict where thrombus formation starts. Additionally, the need of cell-based modelling in these microfluidic devices is demonstrated by comparing our results with macroscopic models, wherein blood is modelled as a continuous fluid. Hemocell, a cell-based blood flow simulation framework is used to investigate the transport physics in the microfluidic devices. The simulations show an enlarged cell-depleted layer at the site where a platelet aggregate forms in the experiments. In this enlarged cell-depleted layer, the probability to find a platelet is higher than in the rest of the microfluidic device. In addition, the shear rates are sufficiently high to allow for the von Willebrand factor to elongate in this region. We hypothesize that the enlarged cell-depleted layer combined with a sufficiently large platelet flux and sufficiently high shear rates result in an haemodynamic environment that is a preferred location for initial platelet aggregation

Inflow and outflow boundary conditions for 2D suspension simulations with the immersed boundary lattice Boltzmann method

In- and outflow boundary conditions for 2D immersed boundary lattice Boltzmann suspension simulations, applied to cell based blood flow models, are presented. The inlet is constructed with an one-way coupling to a periodic domain containing a correct distribution of suspended particles. This provides an inflow of particles that has a correct distribution and is decoupled from any phenomena in the flow domain. An outflow boundary for the particles that does not influence the distribution of particles in the flow domain is also constructed. With this a method to run long ( > 1 s) cell based blood flow simulations within any type of domain is provided. These boundary conditions are then used for a simulation of blood flow in a curved vessel with an aneurysm

Brancherapport curatieve somatische zorg 1998: ontwikkelingen, kengetallen, verdiepingsstudies.

In dit rapport wordt een overzicht gegeven van ontwikkelingen in de curatieve somatische zorg aan de hand van resultaten van onderzoek, kengetallen met betrekking tot gebruik, kosten, middelen en produkties en een aantal verdiepingsstudies op het terrein van de logopedie, spoedeisende medische hulpverlening en intensive care