Page 26 - Improved endothelialization by silicone surface modification and fluid hydrodynamics modulation- Implications for oxygenator biocompatibility Nasim

A challenge to the successful development of biohybrid artificial lungs is to solve the problem of detachment of endothelial cells from the outside surface of hollow fibers when exposed to circulating blood flow. Although a stable collagen coating can be obtained by surface modification methods, cell retention on the outside surface of collagen-coated small diameter hollow fibers used in artificial lungs should be taken into account since cell detachment might leave parts of the thrombogenic collagen coating exposed to blood and subsequently induces platelet adhesion. In Chapter 3, flow preconditioning of endothelial cells seeded on collagen-immobilized AAc-grafted silicone hollow fibers is used to support the endothelial cell monolayer to withstand high fluid shear stress resulting from circulating blood flow. To examine the efficiency of collagen immobilization before cells were seeded, and flow preconditioning of cells after cells were seeded, on the stability and anti-thrombotic functionality of endothelial cells seeded on the outside surface of small diameter hollow fibers under shear stress, a parallel-plate flow chamber was designed and constructed. The precise shear stress distribution in the parallel-plate flow chamber was determined by COMSOL to gain a quantitative correlation between the shear stress and behavior of endothelial cells, e.g. cell detachment and anti-thrombotic function, under controlled experimental conditions.
Collagen is highly thrombogenic, and accelerates platelet aggregation in those areas of a material which are not fully covered by endothelial cells. NO is an important inhibitor of platelet adhesion. NO-releasing material coatings suppress thrombogenic problems in the absence of endothelial cells or in areas which are not fully covered by endothelial cells. As mentioned before, nitrite, the stable end- product of NO metabolism, may represent a potential source of NO in an acidic environment. Whether acidified nitrite indeed prevents platelet adhesion and increases endothelial cell growth has been assessed in Chapter 4. Sodium nitrite- collagen conjugate was immobilized on the inside surface of AAc-grafted large diameter silicone tubes and the effect of nitrite and acidified nitrite release on blood compatibility and endothelialization of silicone tubes was investigated.
A biomaterial surface simultaneously co-immobilized with different biolmolecules can possess the properties of each individual biomolecule. In addition, sustained release of biomolecules from nanoliposomes improves their biological effect. Therefore, in Chapter 5, it was hypothesized that co- immobilization of nanoliposomes possessing anti-thrombotic and growth-inducing properties improves both anticoagulation and endothelialization. Nanoliposomal sodium nitrite (as an anti-thrombotic agent) and nanoliposomal growth hormone (as a growth-inducing agent) were prepared, blended with collagen solution, and then co-immobilized on the inside surface of AAc-grafted large diameter silicone tubes. The amount of nitrite, acidified nitrite, and growth hormone released from surface- modified silicone tubes was determined. Sodium nitrite or growth hormone in the collagen conjugate at concentrations allowing improvement of endothelial cell
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