title: 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.
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor, MI 48109-1055, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor, MI 48109-1055, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Colletta
authors.affiliation: Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR 97331-4003, USA.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Koley
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA.
authors.forename: Chuanwu
authors.initials: C
authors.lastname: Xi
authors.affiliation: Department of Surgery, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-5686, USA.
authors.forename: Terry C
authors.initials: TC
authors.lastname: Major
authors.affiliation: Department of Surgery, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-5686, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor, MI 48109-1055, USA. Electronic address: mmeyerho@umich.edu.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Meyerhoff
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D055499:Catheter-Related Infections / Q000517:prevention & control; D057785:Catheters / Q000382:microbiology*; D004563:Electrochemistry; D048168:Escherichia coli K12 / Q000502:physiology; D009569:Nitric Oxide / Q000737:chemistry*; D011817:Rabbits; D013211:Staphylococcus aureus / Q000502:physiology; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D009569:Nitric Oxide
keywords: Antimicrobial catheters; Copper electrode; Modulated NO release; Nitric oxide; Thromboresistant catheters