Development of nitric oxide-eluting nanocomposite materials using nanoparticles for cardiovascular applications

Abstract

Purpose: To develop nitric oxide (NO)-eluting nanocomposite biomaterials using nanoparticles conjugated with NO donors, which induce anti-thrombogenic properties in the development of cardiovascular devices. Methods: NO-releasing fumed silica nanoparticles (FSNPs) were synthesised via the reaction of S-nitrosothiol NO donors on to the surface of FSNPs. FTIR, NMR, acid titration, and Ellman's tests confirmed the attachment of NO donors on to FSNPs. NO-FSNPs were dispersed in to polyhedral oligomeric silsesquioxane-poly(carbonateurea)urethane (POSS-PCU) nanocomposite polymer at 2, 4, and 8 wt% and bypass grafts were fabricated using extrusion phase inversion techniques. NO release from grafts was measured in a physiological pulsatile flow circuit using the amperometric technique, and their biocompatibility was evaluated in whole blood as a measure of thrombogenicity. Results: The results confirmed the functionalisation of FSNPs with NO donors and release profiles that could be controlled by changing the amount of FSNPs in the polymer matrix. All FSNPs dispersed in to POSS-PCU were capable of NO elution and the optimal release profile was evident with 2 wt% NO-FSNP at physiologically relevant concentrations of ~ 8×10−10 mol cm−2 min−1 over a 7-h period. NOeluting grafts enhanced anti-thrombogenic properties when compared with controls to confirm the protective roles of NO and attenuation of thrombosis. Conclusions: This study used POSS-PCU nanocomposite, already in used in human as tracheal and lacrimal duct conduits. NO-releasing FSNPs were incorporated in to POSS-PCU, and controlled release was confirmed in vitro. NO-eluting bypass grafts with anti-thrombogenic properties represent a newgeneration ofmaterials in the development of cardiovascular devices.