Reduction in Foreign Body Response and Improved Antimicrobial Efficacy via Silicone-Oil-Infused Nitric-Oxide-Releasing Medical-Grade Cannulas

Abstract

Foreign body response and infection are two universal complications that occur with indwelling medical devices. In response, researchers have developed different antimicrobial and antifouling surface strategies to minimize bacterial colonization and fibrous encapsulation. In this study, the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and silicone oil were impregnated into silicone rubber cannulas (SR-SNAP-Si) using a solvent swelling method to improve the antimicrobial properties and decrease the foreign body response. The fabricated SR-SNAP-Si cannulas demonstrated a stable, prolonged NO release, exhibited minimal SNAP leaching, and maintained sliding angles < 15°for 21 days. SR-SNAP-Si cannulas displayed enhanced antimicrobial efficacy against Staphylococcus aureus in a 7-day biofilm bioreactor study, reducing the viability of adhered bacteria by 99.2 ± 0.2% compared to unmodified cannulas while remaining noncytotoxic toward human fibroblast cells. Finally, SR-SNAP-Si cannulas were evaluated for the first time in a 14-and 21-day subcutaneous mouse model, showing significantly enhanced biocompatibility compared to control cannulas by reducing the thickness of fibrous encapsulation by 60.9 ± 6.1 and a 60.8 ± 10.5% reduction in cell density around the implant site after 3 weeks. Thus, this work demonstrates that antifouling, NO-releasing surfaces can improve the lifetime and safety of indwelling medical devices.

Recent Developments in Multifunctional Antimicrobial Surfaces and Applications toward Advanced Nitric Oxide-Based Biomaterials

“…Moreover, the fabricated NO-releasing non-fouling surface was also found to be non-cytotoxic toward mammalian fibroblast cells. A similar methodology was reported with other SR-based medical devices for the use of urinary catheters and insulin cannula with long-term NO release and reduced SNAP leaching and protein fouling in addition to excellent antibacterial, antifouling, and biocompatible properties. ,, This is a simple and promising approach to generate a LINORel surfaces on prefabricated medical devices and therefore holds huge potential in clinical translation. Recently, a novel method to generate NO-releasing Si oil with proactive antibacterial properties was reported that involved covalent immobilization of the NO donor to Si oil or generation of NO-releasing Si oil by nitrosation of thiolated Si oils. , Such oils can be infused on the PDMS surfaces that are often used for biomedical device applications to create antibacterial interfaces.…”

“…(c) SR-SNAP-Si cannulas radically decreased the thickness of the fibrous encapsulation surrounding the implant in the mouse model after 21 days by 60.9 ± 6.1% relative to unmodified cannulas. Reproduced from ref . Copyright 2021 American Chemical Society.…”

“…NO-releasing medical devices made of silicone rubber polymer have shown promising ability to be infused with Si oil to create an antimicrobial and antifouling interface. ,,, Such surfaces can be impregnated with the NO donor SNAP and then later infused with Si oil to generate the antifouling surfaces (Figure B). Reports suggest that infusion with Si oil not only improved the controlled release of NO but also reduced the leaching of SNAP while maintaining the ultralow fouling property of the liquid-infused silicone tubing surface .…”

“…A similar methodology was reported with other SR-based medical devices for the use of urinary catheters and insulin cannula with long-term NO release and reduced SNAP leaching and protein fouling in addition to excellent antibacterial, antifouling, and biocompatible proper- ties. 25,201,207 This is a simple and promising approach to generate a LINORel surfaces on prefabricated medical devices and therefore holds huge potential in clinical translation.…”

Development and In Vitro Whole Blood Hemocompatibility Screening of Endothelium-Mimetic Multifunctional Coatings

“…The instantaneous surface flux of NO from the fabricated incubation vials was assessed before blood exposure following our previously reported methods for blood-contacting materials (see Supporting Methods). 30,31 Total SNAP loading into the PET blood incubation vials was determined by first deswelling circular samples of the SNAP-swollen vials (∼1.03 cm 2 ) in 40% v/v benzyl alcohol in chloroform (1 mL) for 24 h. This process removes SNAP from the polymer and allows detection based on its absorption maximum wavelength (λ max = 340 nm). Using a standard curve, the total mass of SNAP (mg) removed from PET samples after deswelling in solution for 24 h was determined and normalized to the total weight of the sample prior to SNAP removal (mg of SNAP/mg of vial × 100%).…”