Injectable\nand Self-Healing Probiotics-Loaded Hydrogel\nfor Promoting Superbacteria-Infected Wound Healing

Abstract

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