Time‐Responsive Activity of Engineered Bacteria for Local Sterilization and Biofilm Removal in Periodontitis

Periodontitis is a highly prevalent and common condition in people of all ages, however, existing drugs to treat periodontitis have difficulty penetrating complex biofilms. Here, we report a biofilm-penetrating probiotic hybrid strategy for the treatment of periodontitis. It consists of therapeutic probiotics of E. coli Nissle 1917, which can produce antimicrobial peptides and hydrogen, and is coated with D-amino acids that can penetrate biofilms. After the fusion of D-amino acids with the biofilm, EcN entered the plaque biofilm and produced antimicrobial peptides to kill porphyromonas gingivalis and eliminate periodontitis under the action of hydrogen. The efficacy of EcN@DA-D in biofilm penetration and treatment of periodontitis was demonstrated in a rat model of periodontitis. In addition, the clinical combination to construct a rat periodontitis model by using clinical tissue has a significant therapeutic effect. In conclusion, EcN@DA-D offers a promising topical treatment for periodontitis without developing detectable pathogen resistance and side effects.