Page 20 - Improved endothelialization by silicone surface modification and fluid hydrodynamics modulation- Implications for oxygenator biocompatibility Nasim

synthetic hollow fibers might mimic the native pulmonary vasculature and minimize the need for anticoagulants [1, 6]. Synthetic hollow-fiber membranes currently used in artificial lungs do not support endothelial cell adhesion and needs to be surface- modified. After endothelial cell seeding, hollow fibers are bundled and rotated in an oxygenator to create mixing and subsequently reduce boundary layer limits on gas transfer efficiency [1, 5]. If endothelialized hollow fibers in biohybrid artificial lungs can simulate native thromboresistant endothelial surfaces, a major goal will be achieved.
Blood-hollow fibers surface interactions: thrombogenicity
It is well known that shortly after contacting blood (minutes to hours) during ECMO, synthetic hollow fibers are covered with a layer of plasma proteins, predominately albumin, fibrinogen, IgG, fibronectin, and von Willebrand factor prior to the accumulation of inflammatory cells. As this occurs, platelets flowing near the surface end up adhering to the surface followed by activation, thus creating a cascade of events that results in thrombus formation. Platelets do not act in isolation, but as this thrombus formation process is underway, so is the activation of the coagulation cascade by the intrinsic pathway resulting in the release of inflammatory mediators and the production of thrombin, the pivotal agent in the process of thrombosis. Thrombin activates fibrinogen to form the insoluble cross- linked fibrin, which together with activated platelets and red blood cells ultimately leads to thrombus formation [8, 9]. For a detailed explanation of the cellular and molecular mediators of the host foreign body response to biomaterials, see a review by Anderson et al. [10]. In the case of artificial lungs, cell-mediated inflammatory responses and deposition of clots onto hollow fibers can result in bleeding when the blood reenters the patient.
Numerous approaches aimed at developing more blood compatible polymeric materials are currently being investigated in many research laboratories worldwide. Among these, approaches that mimic the highly thromboresistant properties of the normal endothelium appear to be most promising [11-13]. The endothelium is in intimate contact with the blood flow and consists of a single layer of endothelial cells, which functions as a dynamic organ and covers the entire surface of the circulating system from the heart to the smallest capillary [14]. Platelet adhesion/activation and thrombus formation do not readily occur on the surface of a healthy endothelium layer [11, 12]. Then the question to be asked is how normal endothelium does prevent thrombus formation when it is needed within the body. The endothelial cells produce, secrete, and/or express over 12 different inhibitors and activators that affect platelet function, the coagulation cascade, or both [11]. Amongst these factors, nitric oxide (NO) (generated from l-arginine by nitric oxide synthase (NOS) within the endothelial cell), thrombomodulin, prostaglandin I2 (PGI2), and heparins have been investigated most [9, 12].
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