Page 25 - Improved endothelialization by silicone surface modification and fluid hydrodynamics modulation- Implications for oxygenator biocompatibility Nasim

controlled experimental conditions, e.g. stability, morphology, and anti-thrombotic functionality, thereby predicting experimental flow rates that provide optimal device performance [6]. Bioavailability of different biologically active factors released by surface-modified materials or produced by endothelial cells under shear stress can
also be assessed using diffusion-convection physics of CFD [55]. 3
Aim and outline of this thesis
The aim of the studies presented in this thesis was to improve the endothelialization of silicone hollow fibers used in artificial lungs and subsequently increase their biocompatibility by surface modification and fluid hydrodynamic modulation. To achieve this goal, the following questions were addressed:
1. Which functional group, e.g. peroxide, carboxyl and amine, allows strong collagen immobilization and improvement of endothelialization, cell stability, and anti-thrombotic functionality?
2. What is the influence of flow preconditioning of endothelial cells seeded on surface-modified silicone in a parallel-plate flow chamber on cell stability and anti-thrombotic functionality?
3. Does immobilization of nitrite and acidified nitrite generating nitrite sodium- collagen conjugate on acrylic acid-grafted silicone increase the number of endothelial cells as well as growth hormone production and decrease platelet adhesion?
4. Does sustained local release of sodium nitrite (as an anti-thrombotic agent) and growth hormone (as a growth-inducing agent) from nanoliposomes incorporated into collagen coating enhance endothelialization of silicone by increasing the number of endothelial cells, as well as by decreasing platelet adhesion?
5. Is it possible to achieve enhanced bioavailability of anti-thrombotic agents released by surface coating or by endothelial cells under shear stress?
To seek answers to these questions, we started by surface modification of the inside of large diameter silicone tubes with the same chemical composition as silicone hollow fibers used in artificial lungs. In Chapter 2, silicone tubes with three different chemical functional groups, i.e. peroxide, carboxyl, and amine, but similar wettability, were compared to determine the surface chemical entity that allows strong collagen immobilization and improvement of endothelialization, cell stability, and anti-thrombotic functionality. Plasma pre-modification was performed to introduce peroxide groups acting as initiators for graft polymerization. Then silicone tubes containing peroxide groups were graft polymerized with acrylic acid (AAc) to introduce carboxyl groups, or with aminosilane (AmS) to introduce amine groups. Collagen was stably immobilized using carbodiimide bonds on silicone tubes with carboxyl or amine functional groups.
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