More than 75% of hospital-acquired or nosocomial urinary tract infections are initiated by urinary catheters, which are used during the treatment of 15–25% of hospitalized patients. Among other purposes, urinary catheters are primarily used for draining urine after surgeries and for urinary incontinence. During catheter-associated urinary tract infections, bacteria travel up to the bladder and cause infection. A major cause of catheter-associated urinary tract infection is attributed to the use of non-ideal materials in the fabrication of urinary catheters. Such materials allow for the colonization of microorganisms, leading to bacteriuria and infection, depending on the severity of symptoms. The ideal urinary catheter is made out of materials that are biocompatible, antimicrobial, and antifouling. Although an abundance of research has been conducted over the last forty-five years on the subject, the ideal biomaterial, especially for long-term catheterization of more than a month, has yet to be developed. The aim of this review is to highlight the recent advances (over the past 10 years) in developing antimicrobial materials for urinary catheters and to outline future requirements and prospects that guide catheter materials selection and design.

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.

Devices used for extracorporeal circulation are met with two major medical concerns: thrombosis and infection. A device that allows for anticoagulant-free circulation while reducing the risk of infection has yet to be developed. We report the use of a copper nanoparticle (Cu NP) catalyst for the release of nitric oxide (NO) from the endogenous donor S-nitrosoglutathione (GSNO) in a coating applied to commercial Tygon S3 E-3603 poly­(vinyl chloride) tubing in order to reduce the adhered bacterial viability and the occurrence of thrombosis for the first time in an animal model. A Cu GSNO-coated material demonstrated a nitric oxide (NO) release flux ranging from an initial flux of 6.3 ± 0.9 × 10–10 mol cm–2 min–1 to 7.1 ± 0.4 × 10–10 mol cm–2 min–1 after 4 h of release, while GSNO loops without Cu NPs only ranged from an initial flux of 1.1 ± 0.2 × 10–10 mol cm–2 min–1 to 2.3 ± 0.2 × 10–10 mol cm–2 min–1 after 4 h of release, indicating that the addition of Cu NPs can increase NO flux up to five times in the same 4 h period. Additionally, a 3-log reduction in Staphylococcus aureus and 1-log reduction in Pseudomonas aeruginosa were observed in viable bacterial adhesion over a 24 h period compared to control loops. A Cell Counting Kit-8 (CCK-8) assay was used to validate no overall cytotoxicity toward 3T3 mouse fibroblasts. Finally, extracorporeal circuits were coated and exposed to 4 h of blood flow under an in vivo rabbit model. The Cu GSNO combination was successful in maintaining 89.3% of baseline platelet counts, while the control loops were able to maintain 67.6% of the baseline. These results suggest that the combination of Cu NPs with GSNO increases hemocompatibility and antimicrobial properties of ECC loops without any cytotoxic effects toward mammalian cells.

Medical device coatings that resist protein adhesion and bacterial contamination are highly desirable in the healthcare industry. In this work, an antifouling zwitterionic terpolymer, 2-methacryloyloxyethyl phosphorylcholine-co-butyl methacrylate-co-benzophenone (BPMPC), is covalently grafted to a nitric oxide (NO) releasing antimicrobial biomedical grade copolymer of silicone-polycarbonate-urethane, CarboSil, to significantly enhance the biocompatibility, nonspecific protein repulsion and infection-resistant properties. The NO donor embedded into CarboSil is S-nitroso-N-acetylpenicillamine (SNAP) and covalent grafting of the BPMPC is achieved through rapid UV-cross-linking, providing a stable, hydrophilic coating that has excellent durability over a period of several weeks under physiological conditions. The protein adsorption test results indicate a significant reduction (∼84-93%) of protein adhesion on the test samples compared to the control samples. Bacteria tests were also performed using the common nosocomial pathogen, Staphylococcus aureus. Test samples containing both NO donor and BPMPC show a 99.91 ± 0.06% reduction of viable bacteria when compared to control samples. This work demonstrates a synergistic combination of both antimicrobial and antifouling properties in medical devices using NO donors and zwitterionic copolymers that can be covalently grafted to any polymer surface.

Urinary catheterization is one of the most common medical procedures that makes a patient susceptible to infection due to biofilm formation on the urinary catheter. Catheter associated urinary tract infections (CAUTIs) are responsible for over 1 million cases in the United States alone and cost the healthcare industry more than $350 million every year. This work presents a liquid-infused nitric-oxide-releasing (LINORel) urinary catheter fabricated by incorporating the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and silicone oil into commercial silicone Foley catheters through a two-stage swelling process. This synergistic combination improves NO-releasing materials by providing minimal SNAP leaching and a more controlled release of NO while incorporating the nonfouling characteristics of liquid-infused materials. The LINORel urinary catheter was successful in sustaining a controlled NO release over a 60 day period under physiological conditions with minimal SNAP leaching during the initial 24 h period, 0.49 ± 0.0061%. The LINORel-UC proved successful in reducing bacterial adhesion and biofilm formation for Gram positive Staphylococcus aureus (98.49 ± 2.06%) over a 7 day period in a drip flow bioreactor environment. Overall, this study presents a desirable combination that incorporates the antifouling advantages of liquid-infused materials with the active release of a bactericidal agent, an uncharted territory in aiding to prevent the risk of CAUTIs.