Topical application of Clostridium butyricum by an anaerobic hydrogel for accelerated diabetic wound healing through selective bacteria inhibition and ROS scavenging.

Selective inhibition of harmful bacteria without affecting skin symbiotic probiotics and selective scavenging of highly toxic reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and peroxynitrite anions (ONOO-) are new requirements for more precise treatment of diabetic ulcer wounds. Achieving either is challenging, simultaneous achievement remains unreported. Clostridium butyricum (C. butyricum) inherently offers selective antibacterial action and produces hydrogen, specifically scavenging •OH and ONOO-, showing great potential for diabetic wound treatment. However, as an anaerobic bacterium, its anaerobic nature limits topical application in normoxic environments on the skin. To overcome this, we developed a novel hydrogel creating an internal anaerobic microenvironment via the oxygen-depleting reaction between vanillin and laccase. Serving as a carrier, this hydrogel ensures internalized C. butyricum maintains activity in normoxia, enabling effective dual functions: selective bacterial inhibition and selective ROS scavenging. In vivo studies demonstrate the significant efficacy of this C. butyricum-loaded hydrogel in promoting diabetic wound healing. This work pioneers the topical therapeutic use of C. butyricum for wound treatment.