Lysozyme-Responsive Hydrogels of Chitosan-Streptomycin Conjugates for the On-Demand Release of Biofilm-Dispersing Enzymes for the Efficient Eradication of Oral Biofilms

Hydrogels with controlled degradation and sustained antibiofilm activity are promising biomaterials for the treatment of oral infections such as periodontitis or caries. In this article, an in situ forming chitosan-streptomycin hydrogel is developed that can target established bacterial biofilms in response to lysozyme, an enzyme that is overexpressed in saliva during oral infections. When the new hydrogel is applied to simulated oral biofilms, the overexpressed lysozyme degrades the hydrogel and releases chitosan-streptomycin oligosaccharides that can eradicate the biofilm. This work has shown that the coupling of chitosan and streptomycin can have a synergistic effect and that the new hydrogel based on chitosan-streptomycin conjugate can effectively combat biofilms of E. coli, S. aureus, and P. aeruginosa formed in vitro achieving a significant reduction in the biomass of the biofilm and a substantial reduction in the population of viable bacteria in established biofilms. Finally, the CS-Str hydrogel loaded with biofilm-disrupting enzymes, in particular, DNase I and/or DspB, showed a significantly increased ability to reduce the biofilm biomass of P. aeruginosa and S. aureus (by over 84% and up to 92%, respectively), resulting in a drastic reduction in cell viability, which fell below 4% for P. aeruginosa and below 5% for S. aureus.