G.H. Nguyen, M. Garren, M. Clary, V. Pinon, H. Handa, E.J. Brisbois.
University of Georgia,
United States
Keywords: gasotranmitter, antimicrobial, surface modification
Summary:
Current treatment strategies to combat infection, thrombosis, and biofouling, such as antibiotics, anticoagulants, and device replacement, often face limitations, such as bacterial resistance and excessive bleeding and unnecessary platelet consumption. Nitric oxide (NO)-releasing materials have emerged as a promising solution due to their dual bactericidal and platelet-modulating properties. NO inhibits bacterial growth and prevents platelet activation without inducing resistance but cannot prevent biofouling by debris accumulation. Conversely, passive antifouling strategies, such as slippery liquid-infused porous surfaces (SLIPS), effectively repel fouling agents but lack bioactive functionalities. Certain thiolated, aliphatic oils have previously been reported as potential NO donors for a facile solvent impregnation into silicone rubber. However, the antifouling potential presented by the impregnated material was not explored. In this work, the tertiary aliphatic oil tert-dodecylmercaptan (TDM) was nitrosated to yield a NO-releasing lubricant that was swelled into PDMS (TDM-NO) to provide prolonged antibacterial and antifouling efficacy. All samples were freshly prepared before experiments. TDM was initially nitrosated via acidified nitrite and diluted with n-hexadecane in different ratios. The diluted TDM-NO solutions were swelled into PDMS. The materials were characterized by sliding angle measurements, TDM-NO loading and leaching via UV spectroscopy, and NO release through chemiluminescence detection. Cytocompatibility, bactericidal activity, and hemocompatibility were determined by MTT, bacterial adhesion, and platelet adhesion assays, respectively. The initial sliding angle of TDM-NO was below 20° but rapidly increased above 20° after consecutive days of being incubated in 10 mM PBS with 100 μM EDTA under dynamic shaking conditions. It was hypothesized that the branched structure of the TDM prevented the oil from self-replenishing the surface of the substrate, thereby decreasing its slippery capability. Therefore, the nitrosated TDM was diluted with n-hexadecane in different ratios to preserve the slippery functionality. This linear aliphatic oil has been proven to be a slippery lubricant in previous literature and studies. All of the diluted samples also released physiological levels of NO (0.5 – 4 x 10-10 mol min^-1 cm^-2) for 3 to 14 d with TDM-NO-1 exhibiting the longest duration. None of the diluted samples exhibited cytotoxic tendencies towards human BJ fibroblast cells with a relative cell viability > 95% while also significantly reducing the number of adhered S. aureus and E. coli by about 1.70 log and 1.97 log, respectively, during the infection onset period. In addition to the diluted TDM-NO’s cytocompatibility, the material significantly reduced platelet adhesion and fibrinogen adsorption by 67.50% and 60.41%, respectively. This work introduced a slippery, NO-releasing platform that combined the NO-releasing stability of TDM-NO with the slippery behavior of lubricant infusion in one substrate. The PDMS infused with the diluted TDM-NO was able to maintain slippery behavior and physiological levels of NO for at least 7 d. The combination material remained cytocompatible with a relative cell viability greater than 70% while significantly reducing gram-positive S. aureus and gram-negative E. coli adhesion. The material also significantly reduced platelet adhesion and fibrinogen adsorption. Overall, the PDMS infused with diluted TDM-NO demonstrated promising results with potential to be applied in biomedical applications.