Page 21 - Improved endothelialization by silicone surface modification and fluid hydrodynamics modulation- Implications for oxygenator biocompatibility Nasim

Integrating these factors into/on polymer matrices in such a way that they are either
released from the polymers [12, 13, 15], or as immobilized forms of the biologically
active factors on the polymer surfaces [15-18] should result in a truly biomimetic
coating that more closely resembles a layer of functional endothelial cells. What is
unique to these inhibitors, as opposed to those used clinically for platelet inhibition, 3 such as heparin, aspirin, and dipyridamol, is that this inhibition is not permanent for
the platelet’s life, but rather is similar to “anesthesia” of the platelet, so that once
the platelet is no longer exposed to these inhibitors, it resumes normal function [11].
Endothelialization of hollow fibers
Despite extensive research to develop a non thrombogenic surface that mimics the endothelium, platelet activation still occurs, thus these modifications have not completely solved the clinical challenges of platelet passivation [11]. Endothelialized hollow fibers have been suggested as a means to improve artificial lung biocompatibility in new types of artificial lungs, so-called biohybrid artificial lungs [5, 19, 20]. This approach seeks to mimic the in vivo function of vascular endothelial cells to yield a biocompatible surface, actively inhibiting platelet activation and deposition, for long term ECMO support of the lung. By endothelializing hollow fibers that constitute the major blood contacting surface area of the device, the biohybrid artificial lung prototype seeks to significantly reduce or eliminate the need for chronic anticoagulation or anti-platelet agents. The attached endothelial layer provides a naturally occurring biocompatible surface for blood interaction if the cells are maintained as a non-inflammatory, anti-thrombotic phenotype [1, 3, 5].
Surface modification of hollow fiber surfaces to improve endothelialization
The successful development of biohybrid artificial lungs is challenged by the hydrophobic nature of the polymers typically used to make the hollow fibers in ECMO devices, e.g. silicone, which restricts the degree of cell adhesion [5, 6]. Surface modification through physicochemical approaches or bonding biologically adhesive proteins to the hollow fiber surface is required to guarantee endothelial cell attachment and to create a cell monolayer that is robust enough to blood flow shear stress [6, 20].
In the natural endothelium, cells are in intimate contact with the extracellular matrix (ECM), which is formed by a complex connection of proteins, glycoproteins, and proteoglycans, that have a cell-binding domain connecting the ECM–binding sites with intracellular focal adhesion plaques [14, 21]. In this respect the process of endothelial cell adhesion and spreading on hollow fibers in vitro has been shown to be facilitated by pre-coating of substrata with the main ECM protein, collagen [17, 18]. The ability of collagen to support cell adhesion and to trigger
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