Surface fouling is one of the leading causes of infection associated with implants, stents, catheters, and other medical devices. The surface chemistry of medical device coatings is important in controlling and/or preventing fouling. In this study, we have shown that a combination of nitric oxide releasing hydrophobic polymer with a hydrophilic polymer topcoat can significantly reduce protein attachment and subsequently reduce bacterial adhesion as a result of the synergistic effect. Nitric oxide (NO) is a well-known potent antibacterial agent due to its adverse reactions on microbial cell components. Owing to the surface chemistry of hydrophilic polymers, they are suitable as antifouling topcoats. In this study, four biomedical grade polymers were compared for protein adhesion and NO-release behavior: CarboSil 2080A, RTV, SP60D60, and SG80A. SP60D60 was found to resist protein adsorption up to 80% when compared to the other polymers while CarboSil 2080A maintained a steady NO flux even after 24 hours (~0.50 × 10−10 mol cm−2 min−1) of soaking in buffer solution with a loss of less than 3 wt% S-nitroso-N-acetylpenicillamine (SNAP), the NO donor molecule, in the leaching analysis. Therefore, CarboSil 2080A incorporated with SNAP and topcoated with SP60D60, was tested for antibacterial efficacy after exposure to fibrinogen, an abundantly found protein in blood. The NO-releasing CarboSil 2080A with SP60D60 topcoated polymer showed a 96% reduction in Staphylococcus aureus viable cell count compared to the control samples. Hence, the study demonstrated that a hydrophilic polymer topcoat, when applied to a polymer with sustained NO release from underlying SNAP incorporated hydrophobic polymer, can reduce bacterial adhesion and be used as a highly efficient antifouling, antibacterial polymer for biomedical applications.

The development of infection‐resistant materials is of substantial importance as seen with an increase in antibiotic resistance. In this project, the nitric oxide (NO)‐releasing polymer has an added topcoat of zinc oxide nanoparticle (ZnO‐NP) to improve NO‐release and match the endogenous NO flux (0.5–4 × 10−10 mol cm−2 min−1). The ZnO‐NP is incorporated to act as a catalyst and provide the additional benefit of acting synergistically with NO as an antimicrobial agent. The ZnO‐NP topcoat is applied on a polycarbonate‐based polyurethane (CarboSil) that contains blended NO donor, S‐nitroso‐N‐acetylpenicillamine (SNAP). This sample, SNAP‐ZnO, continuously sustained NO release above 0.5 × 10−10 mol cm−2 min−1 for 14 days while samples containing only SNAP dropped below physiological levels within 24 h. The ZnO‐NP topcoat improved NO release and reduced the amount of SNAP leached by 55% over a 7‐day period. ICP‐MS data observed negligible Zn ion release into the environment, suggesting longevity of the catalyst within the material. Compared to samples with no NO‐release, the SNAP‐ZnO films had a 99.03% killing efficacy against Staphylococcus aureus and 87.62% killing efficacy against Pseudomonas aeruginosa. A cell cytotoxicity study using mouse fibroblast 3T3 cells also noted no significant difference in viability between the controls and the SNAP‐ZnO material, indicating no toxicity toward mammalian cells. The studies indicate that the synergy of combining a metal ion catalyst with a NO‐releasing polymer significantly improved NO‐release kinetics and antimicrobial activity for device coating applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A: 000–000, 2019.

Attachment of a nitric oxide (NO) donor to an electrospun polymer has the potential to improve its proliferative and antimicrobial capabilities. This study presents the novel, covalent attachment of S-nitroso-N-acetylpenicillamine (SNAP) to polyacrylonitrile (PAN) fibers. By attaching the NO donor to the polymer, rather than blending it, leaching is reduced to maintain a NO flux within the physiologically relevant range for a longer duration, while limiting any cytotoxic effects. The synthesized fibers were characterized using a variety of techniques such as scanning electron microscopy, 1H NMR, and drop shape analysis. Due to the antimicrobial activity of NO, the SNAP-PAN fibers demonstrated a 2-log reduction of S. aureus adhesion. Furthermore, the extended zone of inhibition of S. aureus by SNAP-PAN demonstrates the ability of NO to impact the environment surrounding the material, in addition to the environment in direct contact with it. The combination of NO release, hydrophilicity of PAN, and the fibrous network led to increased fibroblast proliferation and attachment, potentially expanding the fibers as an improved cell scaffolding platform. The results from this study demonstrate a novel preparation and design of NO-releasing fibers to provide multiple benefits for a variety of biomedical applications.