Lysozyme-Responsive\nHydrogels of Chitosan-Streptomycin\nConjugates for the On-Demand Release of Biofilm-Dispersing Enzymes\nfor the Efficient Eradication of Oral Biofilms

Hydrogels with controlled\ndegradation and sustained antibiofilm\nactivity are promising biomaterials for the treatment of oral infections\nsuch as periodontitis or caries. In this article, an <i>in situ</i> forming chitosan-streptomycin hydrogel is developed that can target\nestablished bacterial biofilms in response to lysozyme, an enzyme\nthat is overexpressed in saliva during oral infections. When the new\nhydrogel is applied to simulated oral biofilms, the overexpressed\nlysozyme degrades the hydrogel and releases chitosan-streptomycin\noligosaccharides that can eradicate the biofilm. This work has shown\nthat the coupling of chitosan and streptomycin can have a synergistic\neffect and that the new hydrogel based on chitosan-streptomycin conjugate\ncan effectively combat biofilms of E. coli, S. aureus, and P.\naeruginosa formed <i>in vitro</i> achieving\na significant reduction in the biomass of the biofilm and a substantial\nreduction in the population of viable bacteria in established biofilms.\nFinally, the CS-Str hydrogel loaded with biofilm-disrupting enzymes,\nin particular, DNase I and/or DspB, showed a significantly increased\nability to reduce the biofilm biomass of P. aeruginosa and S. aureus (by over 84% and up\nto 92%, respectively), resulting in a drastic reduction in cell viability,\nwhich fell below 4% for P. aeruginosa and below 5% for S. aureus.