S-Nitrosoglutathione-Based Nitric Oxide-Releasing Nanofibers Exhibit Dual Antimicrobial and Antithrombotic Activity for Biomedical Applications.

Abstract

The novel use of nanofibers as a physical barrier between blood and medical devices has allowed for modifiable, innovative surface coatings on devices ordinarily plagued by thrombosis, delayed healing, and chronic infection. In this study, the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) is blended with the biodegradable polymers polyhydroxybutyrate (PHB) and polylactic acid (PLA) for the fabrication of hemocompatible, antibacterial nanofibers tailored for blood-contacting applications. Stress/strain behavior of different concentrations of PHB and PLA is recorded to optimize the mechanical properties of the nanofibers. Nanofibers incorporated with different concentrations of GSNO (10, 15, 20 wt%) are evaluated based on their NO-releasing kinetics. PLA/PHB + 20 wt% GSNO nanofibers display the greatest NO release over 72 h (0.4-1.5× 10-10 mol mg-1 min-1 ). NO-releasing fibers successfully reduce viable adhered bacterial counts by ≈80% after 24h of exposure to Staphylococcus aureus. NO-releasing nanofibers exposed to porcine plasma reduce platelet adhesion by 64.6% compared to control nanofibers. The nanofibers are found noncytotoxic (>95% viability) toward NIH/3T3 mouse fibroblasts, and 4',6-diamidino-2-phenylindole and phalloidin staining shows that fibroblasts cultured on NO-releasing fibers have improved cellular adhesion and functionality. Therefore, these novel NO-releasing nanofibers provide a safe antimicrobial and hemocompatible coating for blood-contacting medical devices.