title: Improved Hemocompatibility of Multilumen Catheters via Nitric Oxide (NO) Release from S-Nitroso-N-acetylpenicillamine (SNAP) Composite Filled Lumen.
abstract: Blood-contacting devices, such as intravascular catheters, suffer from challenges related to thrombus formation and infection. Nitric oxide (NO) is an endogenous antiplatelet and antimicrobial agent. Exogenous release of NO from various polymer matrices has been shown to reduce thrombosis and infection of/on implantable medical devices. However, the clinical applications of such materials have been hindered due to factors such as NO donor leaching and thermal instability. In this study, a novel approach is demonstrated in which one lumen of commercial dual lumen catheters is dedicated to the NO release chemistry, allowing the other lumen to be available for clinical vascular access. A composite consisting of poly(ethylene glycol) (PEG) and S-nitroso-N-acetylpenicillamine (SNAP) is used to fill the NO-releasing lumen of commercial 7 French silicone catheters. Physiological levels of NO are released from the SNAP-PEG catheters for up to 14 d, as measured by chemiluminescence NO analyzer (in PBS buffer at 37 °C). PEG facilitates the NO release from SNAP within the lumen by increasing the water absorption and slowly dissolving the solid SNAP-PEG composite. In a CDC biofilm bioreactor, the SNAP-PEG catheters are found to reduce >97% bacterial adhesion as compared to the PEG controls for single bacterial species including E. coli and S. aureus. SNAP-PEG and PEG control catheters were implanted in rabbit veins for 7 h (single lumen) and 11 d (dual lumen) to evaluate their hemocompatibility properties. Significant reductions in thrombus formation on the SNAP-PEG vs PEG controls were observed, with ca. 85% reduction for 7 h single lumen catheters and ca. 55% reduction for 11 d dual lumen catheters.
authors.affiliation: Department of Surgery, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Brisbois
authors.affiliation: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Azmath
authors.initials: A
authors.lastname: Mohammed
authors.affiliation: Department of Surgery, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Terry C
authors.initials: TC
authors.lastname: Major
authors.affiliation: Department of Environmental Sciences, School of Public Health, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Brownstein
authors.affiliation: Department of Environmental Sciences, School of Public Health, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Chuanwu
authors.initials: C
authors.lastname: Xi
authors.affiliation: Department of Biological Engineering, University of Georgia , Athens, Georgia 30602, United States.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Handa
authors.affiliation: Department of Surgery, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
authors.affiliation: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Meyerhoff
mesh_terms: D000818:Animals; D004926:Escherichia coli; D009569:Nitric Oxide / Q000737:chemistry*; D020030:Nitric Oxide Donors; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D013211:Staphylococcus aureus
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine
keywords: S-nitrosothiols; antimicrobial; catheters; hemocompatibility; nitric oxide; poly(ethylene glycol)