A Smart Hydrogel with Anti-Biofilm and Anti-Virulence Activities to Treat Pseudomonas aeruginosa Infections.

Biofilm is the main culprit of refractory infections and seriously threaten to the human health. Here, a smart hydrogel consisted of norspermidine, aminoglycosides, and oxidized polysaccharide is prepared via the formation of acid-labile imine linkage to treat Pseudomonas aeruginosa biofilm infections in several animal models. The increased acidity caused by bacterial infection triggers the release of norspermidine and aminoglycosides covalently bound with the polymer scaffold. The released norspermidine inhibits biofilm formation and virulence production by regulating the quorum sensing of P. aeruginosa, while the aminoglycoside antibiotics effectively kill the released bacteria. The gel thoroughly inhibits biofilm formation on various medical devices and decreases bacteria pathogenicity. It efficiently inhibits implantation-associated biofilm infections and chronic wound infections, and shows great promise to prevent and treat biofilm-induced refractory infection in clinics.