Thromboresistant/anti-biofilm catheters via electrochemically modulated nitric oxide release

Abstract

Inexpensive nitric oxide (NO) release strategies to prevent thrombosis and bacterial infections are desirable for implantable medical devices. Herein, we demonstrate the utility of electrochemically modulated NO release from a catheter model using an inner copper wire working electrode and an inorganic nitrite salt solution reservoir. These catheters generate NO surface fluxes of >1.0 × 10(-10)mol min(-1) cm(-2) for more than 60 h. Catheters with an NO flux of 1.1 × 10(-10)mol min(-1) cm(-2) are shown to significantly reduce surface thrombus formation when implanted in rabbit veins for 7h. Further, the ability of these catheters to exhibit anti-biofilm properties against bacterial species commonly causing bloodstream and urinary catheter infections is examined. Catheters releasing NO continuously during the 2d growth of Staphylococcus aureus exhibit a 6 log-unit reduction in viable surface bacteria. We also demonstrate that catheters generating NO for only 3h at a flux of 1.0 × 10(-10)mol min(-1) cm(-2) lower the live bacterial counts of both 2d and 4d pre-formed Escherichia coli biofilms by >99.9%. Overall, the new electrochemical NO-release devices could provide a cost-effective strategy to greatly enhance the biocompatibility and antimicrobial properties of intravascular and urinary catheters, as well as other implantable medical devices.

Keywords: Antimicrobial catheters; Copper electrode; Modulated NO release; Nitric oxide; Thromboresistant catheters.