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 24 h 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.

Optimized Silica-Binding Peptide-Mediated Delivery of Bactericidal Lysin Efficiently Prevents Staphylococcus aureus from Adhering to Device Surfaces

“…The current pipeline for new antibiotics is drying, which is even more vexatious for healthcare professionals. Currently, clinicians and researchers are forced to look for alternative agents to antibiotics, including bacteriophages and their lysins, antibacterial metal nanoparticles, phytochemicals, antimicrobial peptides, nitric oxide, and other secondary metabolites [36][37][38][39][40][41]. Lysins have gained much popularity because of their high bactericidal properties, rapid killing activity, low risk of resistance, and modular proteinaceous structure.…”

Advances in Polyhydroxyalkanoate Nanocarriers for Effective Drug Delivery: An Overview and Challenges

“…In a recent study, the incorporation of nitric oxide (NO) donor S-nitrosoglutathione (GSNO) onto PHB/PLA nanofibers exhibited dual antibacterial and anti-thrombotic activity [ 100 ]. The NO released from nanofibers was effective in reducing the number of attached S. aureus cells and platelet adhesion by approximately 80% and 65%, respectively [ 100 ]. Li et al developed a stimuli-triggered biocide-loaded PHA-based nanofiber with a core-shell structure [ 101 ].…”

Electrospinning nanofibers of microbial polyhydroxyalkanoates for applications in medical tissue engineering

“…And natural biopolyester materials can make drugs achieve controllable release in time and space, improving the bioavailability of drugs and do not need frequent administration, and can maintain the effective concentration of drugs in vivo for a long time. Furthermore, the selection of EPS materials is very flexible, so many drugs (antisepsis and anti-inflammation, 118,[120][121][122][123][124][125][126] chemotherapy drugs, 127 and others 129,130 ) can be added to the appropriate solution for EPS (Table 5). Analysis of the literature on EPS of natural bio-polyester materials for drug release has been found in recent 10 years, and found that the research and development of drug release are particularly active in the last 5 years.…”