Engineering multifunctional catheters with a nitric oxide-releasing ciprofloxacin conjugate to combat thrombosis and...

Indwelling medical devices, such as intravenous and urinary catheters, have significantly enhanced patient care and greatly improved treatment outcomes. Despite rapid advances in medical devices, infection and thrombosis continue to pose major challenges to device functionality and integrity. Given that current treatments often involve systemic administration of antibiotics and anticoagulants, there is an urgent need for medical devices that are inherently antibacterial and antithrombotic. We explore the chemical conjugation of the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) with the fluoroquinolone-based, broad-spectrum antibiotic Ciprofloxacin (CIP). The combination strategy integrates the directed antibacterial activity of CIP with the antithrombotic and antibiofilm properties of NO. Furthermore, the conjugate molecule (SNAP-CIP) was incorporated into silicone rubber (SR) for catheter fabrication (SR-SNAP-CIP). SR-SNAP-CIP demonstrated 14-day NO-release while remaining biocompatible. The NO release allowed SR-SNAP-CIP to reduce platelet adhesion in vitro by ∼45%. The dual-action material exhibited antibacterial properties when tested in vitro for bacterial adhesion (24 h and 14-day CDC bioreactor), planktonic viability, and biofilm biomass accumulation against S. aureus and E. coli. To assess bacterial migration across the skin barrier, an ex vivo skin translocation model was performed, which showed no bacterial migration on the SR-SNAP-CIP catheter. After the 14-day in vivo rabbit catheter model, SR-SNAP-CIP showed a significant reduction (∼84%) in thrombus area on the catheter and surrounding vein. Furthermore, SR-SNAP-CIP catheters showed a 92% reduction in adhered S. aureus. Overall, SR-SNAP-CIP demonstrated a combination of technologies, harnessing the antibacterial potential of CIP and the antibiofilm and antithrombotic properties of NO. STATEMENT OF SIGNIFICANCE: Despite advancements in biomaterial design, catheter-associated thrombosis and infection persist as primary drivers of device failure and patient morbidity, highlighting the critical need for dual-functioning anti-thrombogenic and antimicrobial interventions. Materials capable of addressing both challenges simultaneously are vital to the development of next-generation, hemocompatible catheter biomaterials. In this work, we present the incorporation of a nitric oxide (NO)-releasing Ciprofloxacin conjugate molecule into a polymer platform to achieve extended NO release and robust antiplatelet activity. The resulting platform demonstrated antibacterial performance in vitro, while remaining cyto- and hemo-compatible. Furthermore, these antibacterial and antithrombotic effects were sustained in a 14-day in vivo rabbit catheter model, indicating strong potential for clinical translation.