Quantification of the Whole Lymph Node Vasculature Based on Tomography of the Vessel Corrosion Casts

Lymph nodes (LN) are crucial for immune function, and comprise an important interface between the blood and lymphatic systems. Blood vessels (BV) in LN are highly specialized, featuring high endothelial venules across which most of the resident lymphocytes crossed. Previous measurements of overall lymph and BV flow rates demonstrated that fluid also crosses BV walls, and that this is important for immune function. However, the spatial distribution of the BV in LN has not been quantified to the degree necessary to analyse the distribution of transmural fluid movement. In this study, we seek to quantify the spatial localization of LNBV, and to predict fluid movement across BV walls. MicroCT imaging of murine popliteal LN showed that capillaries were responsible for approximately 75% of the BV wall surface area, and that this was mostly distributed around the periphery of the node. We then modelled blood flow through the BV to obtain spatially resolved hydrostatic pressures, which were then combined with Starling’s law to predict transmural flow. Much of the total 10 nL/min transmural flow (under normal conditions) was concentrated in the periphery, corresponding closely with surface area distribution. These results provide important insights into the inner workings of LN, and provide a basis for further exploration of the role of LN flow patterns in normal and pathological functions.

Transmural Flow Bioreactor for Vascular Tissue Engineering

There is a clear need for tissue-engineered arteries for procedures such as coronary artery bypass grafts. In nearly one-third of cases, there is no healthy supply of autologous vasculature for grafting due to preexisting conditions or previous surgical intervention [1]. Studies in our lab have focused on fabricating a “media equivalent” or ME as a precursor to a fully endothelialized bioartificial artery. Vascular grafts cultured in vitro are often done so under static conditions with some degree of mechanical stimulation [2, 3] and are thus likely to operate in a diffusional transport regime for nutrient delivery and metabolite removal. In this study, we present an analysis of dissolved oxygen (DO) transport limitations in a statically cultured ME and bioreactor designs that improve transport by controlled perfusion of medium axially and transmurally through the engineered tissue with the goal of achieving stronger and more uniform tissue.

Computational Modeling of LDL and Albumin Transport in an In Vivo CT Image-Based Human Right Coronary Artery

Low wall shear stress (WSS) is implicated in endothelial dysfunction and atherogenesis. The accumulation of macromolecules is also considered as an important factor contributing to the development of atherosclerosis. In the present study, a fluid-wall single-layered model incorporated with shear-dependent transport parameters was used to investigate albumin and low-density lipoprotein (LDL) transport in an in vivo computed tomographic image-based human right coronary artery (RCA). In the fluid-wall model, the bulk blood flow was modeled by the Navier–Stokes equations, Darcy’s law was employed to model the transmural flow in the arterial wall, mass balance of albumin and LDL was governed by the convection-diffusion mechanism with an additional reaction term in the wall, and the Kedem–Katchalsky equations were applied at the endothelium as the interface condition between the lumen and wall. Shear-dependent models for hydraulic conductivity and albumin permeability were derived from experimental data in literature to investigate the influence of WSS on macromolecular accumulation in the arterial wall. A previously developed so-called lumen-free time-averaged scheme was used to approximate macromolecular transport under pulsatile flow conditions. LDL and albumin accumulations in the subendothelial layer were found to be colocalized with low WSS. Two distinct mechanisms responsible for the localized accumulation were identified: one was insufficient efflux from the subendothelial layer to outer wall layers caused by a weaker transmural flow; the other was excessive influx to the subendothelial layer from the lumen caused by a higher permeability of the endothelium. The comparison between steady flow and pulsatile flow results showed that the dynamic behavior of the pulsatile flow could induce a wider and more diffuse macromolecular accumulation pattern through the nonlinear shear-dependent transport properties. Therefore, it is vital to consider blood pulsatility when modeling the shear-dependent macromolecular transport in large arteries. In the present study, LDL and albumin accumulations were observed in the low WSS regions of a human RCA using a fluid-wall mass transport model. It was also found that steady flow simulation could overestimate the magnitude and underestimate the area of accumulations. The association between low WSS and accumulation of macromolecules leading to atherosclerosis may be mediated through effects on transport properties and mass transport and is also influenced by flow pulsatility.