A biodegradable antimicrobial oligomer-containing hydrogel for drug-resistant bacteria-infected skin wound treatment

Antibiotic resistance poses a serious global threat, contributing to severe clinical outcomes such as skin and soft tissue infections. Effective treatment of these infections requires both potent antimicrobial activity against resistant pathogens and wound dressings that can conform closely to the wound site. Degradable antimicrobial polymers offer a promising solution to this challenge. Unlike traditional antibiotic-loaded dressings, which often fail against multidrug-resistant (MDR) bacteria, antimicrobial polymers can effectively overcome resistance barriers. Moreover, these polymers can be easily incorporated into wound dressing materials-hydrogels being a particularly advantageous platform due to their biocompatibility and wound-conforming properties. In this study, we developed a modular strategy to integrate a biodegradable cationic antimicrobial oligomer, oligoamidine (<b>OA1</b>), into a thermo-responsive hydrogel. <b>OA1</b> exerts a triple antibacterial mechanism involving membrane disruption, DNA binding, and ROS generation. The resulting hydrogel system can be conveniently formulated by simple mixing and undergoes a solution-gel transition at body temperature, enabling easy application to infected skin wounds. Importantly, the hydrogel matrix does not impair the bactericidal efficacy of <b>OA1</b>, preserving its full antimicrobial potential. This synergistic system offers an effective and user-friendly approach for treating wounds infected with MDR pathogens.