Modeling of shear stress experienced by endothelial cells cultured on microstructured polymer substrates in a parallel plate flow chamber

Abstract

The application of physical stimuli to cell populations in tissue engineering and regenerative medicine may facilitate significant scientific and clinical advances. However, for the most part, these stimuli are evaluated in isolation, rather than in combination. This study was designed to combine two physical stimuli. The first being a microstructured tissue culture polystyrene substrate, known to produce changes in cell shape and orientation, and the second being laminar shear stress in a parallel plate flow chamber. The combined effects of these stimuli on endothelial cell monolayers cells were evaluated in a parallel plate flow chamber and using a computational fluid dynamics (CFD) model. The topography of the cell monolayers cultured on different microstructured surfaces was determined using confocal laser scanning microscopy (CLSM), and this topographic information was used to construct the CFD model. This research found that while the specific underlying structures were effectively planarized by the cell monolayer, significant differences in cell shape and orientation were observed on the different microstructured surfaces. Cells cultured on grooved substrates aligned in the direction of the grooves and showed higher retention after 1-h LSS conditioning than those cultured on pillars. The modeled shear stress distributions also showed differences. While minor differences in the magnitude of shear stress were noted, aligned cell monolayers experienced significantly lower spatial gradients of shear stress when compared with cells that were not pre-aligned by surface features. The results presented here provide an analysis of how one form of physical stimulus can be moderated by another and also provide a methodology by which the understanding of cell responses to topographic and mechanical stimuli can be further advanced.

Surface projections of titanium substrates increase antithrombotic endothelial function in response to shear stress

“…These studies did not examine the effect of surface topography on gene expression. Other studies have investigated micropillar surface protrusions but only in static culture or under short (1 h) flow conditions . In a study of ECs on surfaces with ordered holes, Morgan et al found that surfaces with holes of various dimensions up to 4 μm pitch did not significantly change the extent of EC or nucleus realignment to flow.…”

“…Liliensiek et al showed that flow primarily determined orientation of ECs adherent on closely spaced (400–800 nm) polyurethane ridges but that surface topography had a greater influence on orientation for larger feature spaces (2000–4000 nm). When fluid shear stress is applied, endothelial cells align and elongate in the direction of flow, which is enhanced if the surface is endowed with long grooves or ridges along the same direction . Likewise, endothelial nuclei align along the direction of grooves, when flow is applied in the same direction as the surface grooves .…”

“…When fluid shear stress is applied, endothelial cells align and elongate in the direction of flow, which is enhanced if the surface is endowed with long grooves or ridges along the same direction. 5,11 Likewise, endothelial nuclei align along the direction of grooves, when flow is applied in the same direction as the surface grooves. 12 Furthermore, grooves enhance surface retention of ECs exposed to flow.…”

“…23 The same effects were noted for ridges of similar spacing. Micropillars of tissue culture polystyrene 3 lm diameter and 0.5 lm height were studied in conjunction with application of flow for 1 h. 11 In these short-term experiments, retention, rather than reorganization with flow, was studied and found to be reduced on the pillar surfaces compared to planar or ridged surfaces. Surface protrusions on titanium surfaces have not been investigated for their ability to support endothelialization.…”

Flow Preconditioning of Endothelial Cells on Collagen‐Immobilized Silicone Fibers Enhances Cell Retention and Antithrombotic Function

“…were solved simultaneously to compute the flow field within the flow chamber : where u is the local velocity, μ is the fluid dynamic viscosity, p is the fluid pressure, and g is the gravity constant. The fluid inlet velocity boundary condition is given as : where V m is the averaged input velocity, z is the direction normal to the flow direction, and H is the height of the parallel‐plate flow chamber. The inlet flow was considered to be nonoscillatory which is consistent with the pump characteristics used in the experiments.…”