Attenuation of Thrombosis and Bacterial Infection using Dual Function Nitric Oxide Releasing Central Venous Catheters in a 9 day Rabbit Model

摘要

Two major problems with implanted catheters are clotting and infection. Nitric oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet adhesion/activation and an antimicrobial agent, and NO-releasing polymers are expected to have similar properties. Here, NO-releasing central venous catheters (CVCs) are fabricated using Elast-eon^™ E2As polymer with both diazeniumdiolated dibutylhexanediamine (DBHD/NONO) and poly(lactic-co-glycolic acid) (PLGA) additives, where the NO release can be modulated and optimized via the hydrolysis rate of the PLGA. It is observed that using a 10 % w/w additive of a PLGA with ester end group provides the most controlled NO release from the CVCs over a 14 d period. The optimized DBHD/NONO based catheters are non-hemolytic (hemolytic index of 0%) and noncytotoxic (grade 0). After 9 d of catheter implantation in the jugular veins of rabbits, the NO-releasing CVCs have a significantly reduced thrombus area (7 times smaller) and a 95% reduction in bacterial adhesion. These results show the promise of DBHD/NONO-based NO releasing materials as a solution to achieve extended NO release for longer term prevention of clotting and infection associated with intravascular catheters.