ABSTRACT
Wound infection and excessive blood loss are the two major challenges associated with trauma injuries that account for 10% of annual deaths in the United States. Nitric oxide (NO) is a gasotransmitter cell signaling molecule that plays a crucial role in the natural wound healing process due to its antibacterial, anti-inflammatory, cell proliferation, and tissue remodeling abilities. Tranexamic acid (TXA), a prothrombotic agent, has been used topically and systemically to control blood loss in reported cases of epistaxis and combat-related trauma injuries. Its properties could be incorporated in wound dressings to induce immediate clot formation, which is a key factor in controlling excessive blood loss. This study introduces a novel, instant clot-forming NO-releasing dressing, and fabricated using a strategic bi-layer configuration. The layer adjacent to the wound was designed with TXA suspended on a resinous bed of propolis, which is a natural bioadhesive possessing antibacterial and anti-inflammatory properties. The base layer, located furthest away from the wound, has an NO donor, S-nitroso-N-acetylpenicillamine (SNAP), embedded in a polymeric bed of Carbosil®, a copolymer of polycarbonate urethane and silicone. Propolis was integrated with a uniform layer of TXA in variable concentrations: 2.5, 5.0, and 7.5 vol % of propolis. This design of the TXA-SNAP-propolis (T-SP) wound dressing allows TXA to form a more stable clot by preventing the lysis of fibrin. The lactate dehydrogenase-based platelet adhesion assay showed an increase in fibrin activation with 7.5% T-SP as compared with control within the first 15 min of its application. A scanning electron microscope (SEM) confirmed the presence of a dense fibrin network stabilizing the clot for fabricated dressing. The antibacterial activity of NO and propolis resulted in a 98.9 ± 1% and 99.4 ± 1% reduction in the colony-forming unit of Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii, respectively, which puts forward the fabricated dressing as an emergency first aid for traumatic injuries, preventing excessive blood loss and soil-borne infections.
ABSTRACT
Infection of indwelling catheters is a common healthcare problem, resulting in higher morbidity and mortality. The vulnerable population reliant on catheters post-surgery for food and fluid intake, blood transfusion, or urinary incontinence or retention is susceptible to hospital-acquired infection originating from the very catheter. Bacterial adhesion on catheters can take place during the insertion or over time when catheters are used for an extended period. Nitric oxide-releasing materials have shown promise in exhibiting antibacterial properties without the risk of antibacterial resistance which can be an issue with conventional antibiotics. In this study, 1, 5, and 10 wt % selenium (Se) and 10 wt % S-nitrosoglutathione (GSNO)-incorporated catheters were prepared through a layer-by-layer dip-coating method to demonstrate NO-releasing and NO-generating capability of the catheters. The presence of Se on the catheter interface resulted in a 5 times higher NO flux in 10% Se-GSNO catheter through catalytic NO generation. A physiological level of NO release was observed from 10% Se-GSNO catheters for 5 d, along with an enhanced NO generation via the catalytic activity as Se was able to increase NO availability. The catheters were also found to be compatible and stable when subjected to sterilization and storage, even at room temperature. Additionally, the catheters showed a 97.02% and 93.24% reduction in the adhesion of clinically relevant strains of Escherichia coli and Staphylococcus aureus, respectively. Cytocompatibility testing of the catheter with 3T3 mouse fibroblast cells supports the material's biocompatibility. These findings from the study establish the proposed catheter as a prospective antibacterial material that can be translated into a clinical setting to combat catheter-related infections.
