Hydrogel effects rapid biofilm debridement with ex situ contact-kill to eliminate multidrug resistant bacteria in vivo

Abstract

Multi-drug resistance and the refractory character of bacterial biofilms are among the most difficult challenges in infection treatment. Current antimicrobial strategies typically are much more effective for prevention of biofilm formation than for eradication of established biofilms; these strategies also leave dead bacteria and endotoxin in the infection site, which impairs healing. We report a novel hydrogel that eradicates biofilm bacteria by non-leaching-based debridement followed by ex-situ contact-killing (DESCK) away from the infection site. The debridement effect is likely due to the high water swellability and microporosity of the crosslinked network which is made from polyethylene glycol dimethacrylate tethered with a dangling polyethylenimine (PEI) star copolymer. The large pore size of the hydrogel makes the cationic pore walls highly accessible to bacteria. The hydrogel also degrades in the presence of infection cells, releasing star cationic PEI into the infection site to contact-kill bacteria remaining there. DESCK hydrogel effectively kills (>99.9% reduction) biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CR-PA) and Acinetobacter baumannii (CR-AB) in a murine excisional wound infection model. Silver-based wound dressings (controls) showed almost no killing of CR-PA and MRSA biofilms. This DESCK hydrogel greatly reduces the bioburden and inflammation, and promotes wound healing. It has great potential for diverse infection treatment applications.