Biocompatibility and Safety Assessment of Combined Topical Ozone and Antibiotics for Treatment of Infected Wounds.

Wound infections with antibiotic-resistant bacteria, particularly the Gram-negative strains, pose a substantial health risk for patients with limited treatment options. Recently topical administration of gaseous ozone and its combination with antibiotics through portable systems has been demonstrated to be a promising approach to eradicate commonly found Gram-negative strains of bacteria in wound infections. However, despite the significant impact of ozone in treating the growing number of antibiotic-resistant infections, uncontrolled and high concentrations of ozone can cause damage to the surrounding tissue. Hence, before such treatments could advance into clinical usage, it is paramount to identify appropriate levels of topical ozone that are effective in treating bacterial infections and safe for use in topical administration. To address this concern, we have conducted a series of in vivo studies to evaluate the efficacy and safety of a portable and wearable adjunct ozone and antibiotic wound therapy system. The concurrent ozone and antibiotics are applied through a wound interfaced gas permeable dressing coated with water-soluble nanofibers containing vancomycin and linezolid (traditionally used to treat Gram-positive infections) and connected to a portable ozone delivery system. The bactericidal properties of the combination therapy were evaluated on an ex vivo wound model infected with Pseudomonas aeruginosa, a common Gram-negative strain of bacteria found in many skin infections with high resistance to a wide range of currently available antibiotics. The results indicated that the optimized combination delivery of ozone (4 mg h-1) and topical antibiotic (200 µg cm-2) provided complete bacteria eradication after 6 h of treatment while having minimum cytotoxicity to human fibroblast cells. Furthermore, in vivo local and systemic toxicity studies (e.g., skin monitoring, skin histopathology, and blood analysis) on pig models showed no signs of adverse effects of ozone and antibiotic combination therapy even after 5 days of continuous administration. The confirmed efficacy and biosafety profile of the adjunct ozone and antibiotic therapy places it as a strong candidate for treating wound infection with antimicrobial-resistant bacteria and further pursuing human clinical trials.

Low-Cost Flexible Glass-Based pH Sensor via Cold Atmospheric Plasma Deposition.

Many commercially available pH sensors are fabricated with a glass membrane as the sensing component because of several advantages of glass-based electrodes such as versatility, high accuracy, and excellent stability in various conditions. However, because of their bulkiness and poor mechanical properties, conventional glass-based sensors are not ideal for wearable or flexible applications. Here, we report for the first time the fabrication of a flexible glass-based pH sensor suitable for biomedical and environmental applications where flexibility and stability of the sensor are critical for long-term and real-time monitoring. The sensor was fabricated via a simple and facile approach using the cold atmospheric plasma technique in which a pH sensitive silica coating was deposited from a siloxane precursor onto a carbon electrode. In order to increase the sensitivity and stability of the sensor, we employed a postprocessing step which involves annealing of the silica coated electrode at elevated temperatures. This process was optimized to ensure that the crucial properties such as porosity and hydration functionality were balanced to obtain the best and most reliable sensitivity of the sensor. Our sensitivity test results indicated that these sensors exhibit excellent and stable sensitivity with a slope of about 48 mV/pH (r2 = 0.998) and selectivity across a pH range of 4 to 10 in the presence of various cations. The optimized sensor has shown stable sensitivity for a long period of time (30 h of immersion) and in different bending conditions. We demonstrate in this investigation that this flexible cost-effective pH sensor can withstand the sterilization process resulting from ultraviolet radiation and shows repeatable sensitivity with less than ±5 mV potential drift from the sensitivity values of the standard optimized sensor.