Page 33 - Improved endothelialization by silicone surface modification and fluid hydrodynamics modulation- Implications for oxygenator biocompatibility Nasim

INTRODUCTION
Extracorporeal membrane oxygenation using blood oxygenators, e.g. microporous
hollow fiber membrane oxygenators, also called artificial lungs, is a strategy used
to support the function of natural lungs [1-3]. Long term usage of microporous
hollow fibers is limited, since plasma-wetting causes plasma to break through the micropores of the capillaries into the gas phase, and poor biocompatibility of hollow
fibers causes thrombosis [1, 4, 5]. The plasma-wetting problem can be solved by
using non-porous silicone membrane hollow fibers or diffusive capillary-form
silicone hollow spheres [6]. However the poor biocompatibility of silicone 3 membranes is still a key limitation for clinical application of silicone-based artificial
lungs [5, 7].
Tissue engineering is used to increase the biocompatibility of silicone
membranes in new types of artificial lungs, so-called biohybrid artificial lungs [4, 5, 8]. The blood-contacting parts of silicone membranes in biohybrid artificial lungs are seeded with endothelial cells to provide a naturally occurring biocompatible surface for blood interaction [8-10]. The success of endothelialization of blood- contacting silicone membranes is highly dependent on the interaction of endothelial cells with the material’s surface (i.e. cell adhesion, proliferation, stability, anti- thrombotic functionality) [11] depend on material surface reactive groups [12, 13], surface charge [11, 14], and immobilized adhesive proteins such as collagen, gelatin, and fibronectin [15-17]. The silicone surface is hydrophobic with a low surface energy, chemically inert, and nonpolar, and does not support the growth and function of adhesion-dependent cells [12]. Therefore principal surface modification is needed to improve cell-silicone interactions [15, 18]. Plasma graft modification involves surface activation with plasma followed by substrate exposure to a grafting monomer [19-22], and provides different functional groups with different surface charges based on the monomer used. The functional groups are main reactive groups amenable for covalent immobilization of extracellular matrix proteins [16, 17]. These proteins enhance the attachment and proliferation of endothelial cells [14, 15, 17, 23].
Plasma graft polymerization creates a strong covalent surface modification, which is essential to obtain surfaces that are robust enough to withstand circulating blood flow shear stresses2in biohybrid artificial lungs [5]. This fluid shear stress has been estimated 1–3 N/m , except at the entrance point of the device, where the shear stress is much higher [24]. Cell detachment from the material surface as a result of fluid shear stress might result in platelet formation in regions that are not fully covered with endothelial cells [25, 26]. Not only stable endothelial cell adhesion and proliferation, but also endothelial cell functionality on surface- modified materials is important when endothelial cell seeding is used to improve the biocompatibility of artificial lungs. Since NO inhibits platelet aggregation and
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