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

Abstract 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.