Poster N18 - Antibacterial Ultra-Slippery Surfaces for Urological Catheter Applications with Nitric Oxide Release and Liquid-Infused Interface

Introduction: Bacterial colonization and biofilm formation on urinary catheter surfaces remain a significant threat leading to severe infections and device failure. Consequently, there's a growing interest in antimicrobial solutions to prevent microbial attachment and biofilm development, particularly for therapeutic applications. Nitric Oxide (NO) is recognized for its antimicrobial and anti-inflammatory properties, making it a valuable tool in combating medical device infections [1]. Polymers that release NO at physiological levels demonstrate broad-spectrum antimicrobial efficacy. Recent studies have demonstrated the compatibility of slippery, liquid-infused porous surfaces (SLIPs) with an ability to engender ultralow fouling surfaces that are impervious to protein adsorption and bacterial adhesion using Food & Drug Administration (FDA)-approved silicone oil (Si) [2]. Current clinical strategies to prevent catheter-associated infections face challenges such as antibiotic resistance and limited effectiveness of antibiotics and antiseptics, underscoring the need for broad-spectrum solutions compatible with the body. This project aims to develop long-term, cost-effective catheters that overcome these limitations by preventing infection and device fouling without frequent replacement. For this, the NO donor S-nitroso-N-acetylpenicillamine (SNAP) and Si oil were sequentially loaded into commercial Foley catheters. The resultant liquid-infused NO-releasing (LINORel) urinary catheters were investigated for swelling ratio, sliding angle, real-time NO release, SNAP leaching, protein adsorption, sterilization compatibility, cytocompatibility, and antibacterial properties, crucial for facilitating clinical translation.

Materials and

Methods: To generate LINORel catheters, commercial 18 Fr silicone Foley catheters (BARD) were modified via solvent-swelling. First, 1 cm segments of silicone Foley catheter were submerged into the NO donor SNAP-THF solution (125 mg/mL) for 24 h. Subsequently, samples were dried in a vacuum desiccator for another 24 h and then infused with 50 cSt Si oil to create SLIPs. The resulting LINORel catheters were dried and used for further analysis. To determine the real-time NO release, the LINORel catheters were submerged in 10 mM PBS with 100 µM EDTA at 37 °C and measured for the NO release up to 14 d using a chemiluminescence Nitric Oxide Analyzer 280i (Zysense, Frederick, CO). The SNAP leaching from catheters was investigated using UV-Vis spectroscopy at 340 nm wavelength. Further, the antifouling ability of catheters was assessed via Bovine Serum Albumin (BSA; 200 mg/L) adsorption for up to 24 h. Finally, the cytocompatibility and antibacterial activity of LINORel catheters were tested against 3T3 mouse fibroblast cells and P. mirabilis bacteria using a 14 d CDC bioreactor, respectively.

Results, Conclusions, and Discussions: The LINORel catheters exhibited a sliding angle of < 5° for at least 14 d and released NO at physiological levels, with minimal leaching of SNAP. The incorporation of SNAP and Si oil in the catheters resulted in a 56.5% decrease in protein adsorption. Furthermore, the LINORel catheters demonstrated > 70% cell viability and led to a 2-log reduction in P. mirabilis adhesion on the surface (Figure 1). The LINORel Foley catheters provide a multifaceted antimicrobial surface that is cost-effective, cytocompatible, and simple to produce. This study emphasizes the importance of integrating both active (SNAP) and passive (Si oil) components into a unified polymer system. Moreover, this approach can be seamlessly integrated into other indwelling medical devices such as insulin cannulas, endotracheal tubing, etc. that face similar challenges with bacteria and biofilm, enhancing their efficacy and safety.

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