Nanoliposomal Growth Hormone and Sodium Nitrite Release from Silicone Fibers Reduces Thrombus Formation Under Flow.

Abstract

Biocompatibility of artificial lungs can be improved by endothelialization of hollow fibers. Bioavailability of growth-inducing and anti-thrombotic agents on the hollow fiber-blood interface inhibits thrombosis. We investigated if nanoliposomal growth-inducing growth hormone (nGH) and anti-thrombotic sodium nitrite (nNitrite) incorporation into collagen-coating on silicone hollow fibers improves blood biocompatibility by increasing endothelial cell growth and nitrite bioavailability under flow. Nitrite production rate was assessed under varying flow conditions. Finite element (FE) modeling was used to simulate nitrite transport within the parallel-plate flow chamber, and nitrite bioavailability on the fiber-blood interface at 1-30dyn/cm(2) shear stress. Endothelial cell number on fibers coated with nNitrite-nGH-collagen conjugate was 1.5-fold higher than on collagen-coated fibers. For collagen-coated fibers, nitrite production reached a maximum at 18dyn/cm(2) shear stress. When fibers were coated with nNitrite-nGH-collagen conjugate, nitrite production increased continuously by increasing shear stress. FE modeling revealed that nitrite concentrations at the fiber-blood interface were affected by shear stress-induced nitrite production, and diffusion/convection-induced nitrite removal. Highest nitrite concentrations and lowest thrombus deposition were observed on fibers coated with nNitrite-nGH-collagen conjugate exposed to 6-12dyn/cm(2) shear stress. In conclusion, our results suggest that nNitrite-nGH-Col conjugate coatings promote endothelialization of silicone hollow fibers in biohybrid artificial lungs.