Liquid-infused nitric oxide-releasing (LINORel) silicone for decreased fouling, thrombosis, and infection of medical devices

Abstract

Recent reports on liquid-infused materials have shown promise in creating ultra-low fouling surfaces, but are limited in their ability to prevent bacterial proliferation and prevent platelet activation in blood-contacting applications. In this work, a liquid-infused nitric oxide-releasing (LINORel) material is created by incorporating the nitric oxide (NO) donor S-nitroso-acetylpenicillamine (SNAP) and silicone oil in commercial medical grade silicone rubber tubing through a solvent swelling process. This combination provides several key advantages over previous NO-releasing materials, including decreased leaching of NO donor, controlled release of NO, and maintenance of ultra-low fouling property of liquid-infused materials. The LINORel tubing reduces protein adhesion as observed using fluorescence imaging, and platelet adhesion (81.7 ± 2.5%) in vitro over a 2 h period. The LINORel combination greatly reduces bacterial adhesion and biofilm formation of two most common pathogens responsible for hospital acquired infections: gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa (99.3 ± 1.9% and 88.5 ± 3.3% respectively) over a 7-day period in a CDC bioreactor environment. Overall, the LINORel approach provides a synergistic combination of active and passive non-fouling approaches to increase biocompatibility and reduce infection associated with medical devices.

Figure 1

(A) Swelling of silicone rubber tubing with silicone oil in control and SR tubing infused with SNAP. Error bars are on the order of data point size and therefore not shown. (B) Sliding angle of LI-SR and LINORel-SR tubing over 7 d when stored in phosphate buffered saline at 37 °C.

Figure 2

Leaching characteristics of SNAP from NORel-SR and LINORel-SR. Leaching was conducted at room temperature for oil swelling, and physiological conditions (PBS, 37 C). Samples were protected from light at all times.

Figure 3

(A) Average daily nitric oxide release measures from NORel-SR and LINORel-SR tubing over a 7-day period. Measurements were conducted at 37 °C using a Sievers Chemiluminescence Nitric Oxide Analyzer. (B) Cummulative release of NO from NORel-SR and LINORel at physiological conditions due to leaching and degredation of the NO donor.

Figure 4

Assessment of protein adhesion (FITC labeled fibrinogen) after 2 h incubation on (A) SR (B) LI-SR, (C) NOrel-SR, (D) LINORel-SR. Scale bar represents 250 µm.

Figure 5

Degree of platelet adhesion on various silicone tubing after 2 h exposure to porcine platelet rich plasma as measured using an LDH quantification assay.

Figure 6

Viable bacteria on various silicone tubing after 7 d bacteria exposure in a CDC bioreactor.

Figure 7

Cytocompatbility and cell growth support of various infused SR tubing towards mouse fibroblast cells in 24 h study.