Smart Wearable Ozone Therapy System for Managing Multidrug-Resistant Wound Infections

Abstract

Multidrug-resistant (MDR) bacterial infections represent a critical challenge in wound care, leading to treatment failure, prolonged healing, and increased morbidity and mortality worldwide. Among MDR pathogens, Pseudomonas aeruginosa is particularly problematic due to its adaptive resistance mechanisms, underscoring the urgent need for alternative, non-antibiotic therapeutic strategies. Ozone has demonstrated potent antimicrobial efficacy while promoting wound healing and exhibiting a low propensity for resistance development; however, conventional ozone delivery systems are bulky, poorly suited for ambulatory use, and pose risks of environmental leakage and unintended exposure. To address these limitations, we have developed a smart wearable ozone therapy system capable of precise, localized ozone delivery directly to the wound bed. The platform integrates on-demand ozone generation, real-time sensing, and controlled air circulation within a compact, reusable unit, coupled to a disposable wound interface patch via double-lumen tubing. Embedded sensors continuously regulate ozone concentrations within therapeutic windows while detecting leakage and triggering automatic shutdown to ensure patient and environmental safety. System characterization demonstrated that localized low-level ozone exposure (75 ppm), when combined with Vancomycin (400 µg·mL⁻¹), eradicated planktonic bacterial cultures to undetectable levels within 4 h while maintaining minimal cytotoxicity toward mammalian cells. For the first time, this fully integrated wearable platform was validated in a Pseudomonas aeruginosa–infected porcine wound model, achieving approximately 90% bacterial reduction after four consecutive daily 6 h treatments and accelerating wound closure by nearly threefold compared with silver dressings or topical antibiotic treatment alone. These results establish a safe, effective, and translationally viable wearable ozone therapy system for the management of MDR-infected wounds.