Injectable and Self-Healing Probiotics-Loaded Hydrogel for Promoting Superbacteria-Infected Wound Healing

Abstract

Superbacteria-induced skin wound infections are huge health challenges, resulting in significant financial and medical costs due to notable morbidity and mortality worldwide. Probiotics are found in the skin and are effective in treating bacterial infection, moderating the microbial dysbiosis and inflammation induced by pathogens, regulating the immune system, as well as even promoting tissue repair. However, improving their colonization efficiency and viability remains a large obstacle for proper applications. Inspired by probiotic therapy and the natural extracellular matrix structure, hyaluronate-adipic dihydrazide/aldehyde-terminated Pluronic F127/fucoidan hydrogels loaded with <i>Lactobacillus rhamnosus</i> ([e-mail]) with unique (bio)physicochemical characteristics were developed through the dynamic Schiff-base reaction for superbacteria-infected trauma management. The developed [e-mail] exhibit a shortened gelation time, enhanced mechanical strength, and excellent self-healing and liquid-absorption abilities. Importantly, their anti-superbacteria (<i>Pseudomonas aeruginosa</i>) effect was greatly increased in a dose-dependent fashion. Additionally, <i>in vitro</i> evaluation shows that the prepared [e-mail] containing appropriate probiotic concentrations (less than 1 × 10⁷ CFU/mL) possess satisfactory cytocompatibility and blood compatibility. Further, compared to the HPF hydrogel, <i>in vivo</i> the hydrogel combined with probiotics significantly inhibits <i>P. aeruginosa</i> infection and inflammation, promotes the formation of re-epithelialization and collagen, and thus accelerates full-thickness superbacteria-infected wound repair, which is comparable to commercial Prontosan gel formulation. This work suggests that the combination of biomimicking hydrogels and probiotic therapy displays the great potential to manage superbug-infected trauma.