Page 24 - Improved endothelialization by silicone surface modification and fluid hydrodynamics modulation- Implications for oxygenator biocompatibility Nasim

Shear stress conditioning of endothelial cell-seeded hollow fibers
In addition to stable collagen conjugate coating, cell retention on surface-modified hollow fibers is important, since cell detachment might lead to the formation of platelet aggregates in regions where blood is in direct contact with protein coating, instead of endothelial cells [21, 24]. A promising way to enhance endothelial cell retention onto a surface-modified material is shear stress preconditioning of cells with shear stresses lower than those present in the biomedical device [21, 39-41]. Under chronic shear stress, endothelial cells flatten, structurally remodel to spread the shear stress over greater surface area, and therefore increase their adherence to the substratum through focal contacts [42, 43]. The production of endothelial cell-derived anti-inflammatory agents, e.g. NO and PGI2, can increase by fluid shear stress [25, 44, 45].
Parallel-plate flow chambers are the most commonly used devices used to investigate the cellular response to fluid shear stress [44-47]. Calculating the exact amount of applied shear stress in these devices by mathematical modeling is very important to gain a quantitative relationship between fluid changes and cell biologic responses. A common mathematical model used to predict shear stresses in these devices employs the use of the Navier-Stokes equation for steady, pressure-driven flow between two parallel-plates with a no slip boundary condition applied to the surface of the plates, resulting in parabolic Poiseuillian flow [48]. In such models of flat plate flow, the calculation of the wall shear stress may be easily accomplished from a known velocity gradient normal to the surface. However, when various types of surface roughness, such as presence of hollow fibers or considering endothelial cell layer, are incorporated into the plate, the flow at the surface is altered and direction normal to the surface is not the same in all locations, increasing the complexity in the determination of wall shear stress [46]. To better realize the effect of flow in these complicated environments, computational fluid dynamics (CFD) has been used as a reliable technique [49-52]. CFD can reveal a detailed profile of pressure, velocity, flow fields, shear stresses, and oxygen transfer in cell or tissue culture chambers of various bioreactor designs [52]. This is useful for the design optimization of internal geometric configurations of bioreactors.
Since the local fluid dynamics, especially the shear stress arising from the blood flow, cannot be analyzed experimentally, CFD is essential for estimating the blood shear stress which acts on platelets when developing blood-contacting devices [49, 50]. The blood flow pattern in artificial lungs is complicated and difficult to measure, and thus CFD has been extensively used to study the effects of packing of hollow fibers, and structure of the artificial lung on the oxygen transfer and blood trauma [53, 54]. In biohybrid artificial lungs a detailed flow field computation represents a unique opportunity to gain a qualitative correlation between the specific wall shear stress distribution over the endothelial cell-seeded hollow fibers and the biological behavior typical for endothelial cells under
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