Catalyzed Nitric Oxide Release via Cu Nanoparticles Leads to an Increase in Antimicrobial Effects and Hemocompatibility for Short-Term Extracorporeal Circulation

Devices used for extracorporeal circulation are met with two major medical concerns: thrombosis and infection. A device that allows for anticoagulant-free circulation while reducing risk of infection has yet to be developed. We report the use of a copper nanoparticle (Cu NP) catalyst for the release of nitric oxide (NO) from the endogenous donor S-nitrosoglutathione (GSNO) in a coating applied to commercial Tygon S3^™ E-3603 poly(vinyl chloride) tubing in order to reduce adhered bacterial viability and the occurrence thrombosis for the first time in an animal model. Cu GSNO coated material demonstrated a nitric oxide (NO) release flux ranging from an initial flux of 6.3 ± 0.9 ×10^-10 mol cm^-2 min^-1 to 7.1 ± 0.4 ×10^-10 mol cm^-2 min^-1 after 4 h of release, while GSNO loops without Cu NPs only ranged from an initial flux of 1.1 ± 0.2 ×10^-10 mol cm^-2 min^-1 to 2.3 ± 0.2 ×10^-10 mol cm^-2 min^-1 after 4 h of release, indicating that the addition of Cu NPs can increase NO flux up to five times in the same 4 h period. Additionally, a 3-log reduction in S. aureus and 1-log reduction in P. aeruginosa was observed in viable bacterial adhesion over a 24 h period compared to control loops. A Cell Counting Kit-8 (CCK-8) assay was used to validate no overall cytotoxicity towards 3T3 mouse fibroblasts. Finally, extracorporeal circuits were coated and exposed to 4 h of blood flow under an in vivo rabbit model. The Cu GSNO combination was successful in maintaining 89.3% of baseline platelet counts, while the control loops were able to maintain 67.6% of the baseline. These results suggest that the combination of Cu NPs with GSNO increases hemocompatibility and antimicrobial properties of ECC loops without any cytotoxic effects towards mammalian cells.