Bacterial enzyme-responsive hydrogels for triggered delivery of antibiotics to infected wounds

Wound infections are becoming increasingly difficult to treat due to rising antibiotic-resistant bacteria. β-Lactamase–producing bacteria are among the most common pathogens implicated in these infections. Here, we report a bacterial enzyme-responsive hydrogel formulated with a cephalosporin-derived, β-lactamase–cleavable crosslinker that undergoes selective degradation in the presence of bacterial β-lactamases. This degradation triggers the on-demand release of encapsulated ciprofloxacin-loaded liposomes, ensuring that antibiotic delivery occurs only at the site of infection. This selective degradation and release was demonstrated in both ex vivo and in vivo models of Pseudomonas aeruginosa wound infections. In a murine skin abrasion infection model, a single application of the hydrogel led to complete bacterial eradication and enhanced wound healing, outperforming a commercial silver-based hydrogel wound dressing. These responsive hydrogels did not induce ciprofloxacin resistance in non–β-lactamase–producing bacteria. These findings demonstrate that β-lactamase–responsive hydrogels provide a precise, infection-triggered antibiotic delivery platform that can improve the treatment of wound infections and mitigate antimicrobial resistance.