Page 22 - Improved endothelialization by silicone surface modification and fluid hydrodynamics modulation- Implications for oxygenator biocompatibility Nasim

signals promoting cell proliferation has been shown to be dependent on its quantity, conformation, and activity, which are influenced by the surface properties of the underlying substratum [22, 23]. Despite of its positive effects on cell adhesion and proliferation, collagen is highly thrombogenic, and induces both platelet adhesion and aggregation as well as activation of the intrinsic coagulation cascade in areas which are not fully covered by endothelial cells [24]. Therefore, promotion of endothelial cell growth by ECM molecules causes the blood compatibility to deteriorate, whereas improvement of antithrombogenicity by the anticoagulant molecules inhibits endothelial cell growth [16]. Most studies focus on one aspect of biocompatibility, i.e. blood compatibility by anti-thrombotic agents, or cytocompatibility by endothelialization [11-13], while less reports exist considering both aspects [16-18, 24]. NO is an important inhibitor of platelet adhesion [11-15]. Treatment of endothelial cells by shear stress, cold temperature, and aspirin stimulates NO production and decreases thrombus formation [25]. NO-releasing material coatings suppress thrombogenic problems in the absence of endothelial cells or in areas which are not fully covered by endothelial cells [12, 13]. Nitrite, the stable end-product of NO metabolism, may represent a potential source of NO in an acidic environment [26, 27]. Therefore conjugation of collagen with NO-donor molecules might increase endothelial cell attachment and decrease thrombotic properties of collagen when it is not completely covered by endothelial cells.
The ultimate success of endothelialization of materials depends on the confluency of the cellular layer [24, 28]. Several hundreds of millions of cells are needed to coat the hollow fibers of one meter squared artificial lung [29]. Therefore, it takes a long period of time to reach confluency of the cell layer on hollow fibers when cells are seeded at low cell densities. Sustained release of growth-inducing agents, e.g. growth factors or growth hormones, may possibly accelerate the formation of a confluent cell layer [24]. Endothelial cells could then be seeded at a density forming a sub-confluent layer on hollow fibers, and subsequently be stimulated by growth-inducing agents to rapidly form a confluent monolayer. Growth hormone, also known as somatropin, is such a growth-inducing agent, since it is a mitogen for a variety of cell types, including smooth muscle cells, fibroblasts, adipocytes, macrophages, lymphocytes, and endothelial cells [30]. Growth hormone treatment of endothelial cells reduces intracellular reactive oxygen species production and regulates the synthesis of multiple mRNA species, including that of insulin-like growth factor-1 and eNOS [30].
Current therapeutic use of anti-thrombotic or growth-inducing agents is limited by their short half life, renal toxicity, physical and chemical instability, and rapid clearance [31]. These limitations might be overcome by controlled prolonged release of biological agents from liposome-based particles. Liposome-based particles, especially nanoliposomes, have gained considerable attention as drug delivery carriers because they are biocompatible, biodegradable, and capable of
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