Bacteriophage lysin-MOFs nanomaterials for treating apical periodontitis.

Enterococcus Faecalis (E. faecalis) infection is a leading cause of refractory apical periodontitis (RAP), where persistent inflammation and bone resorption contribute to poor healing outcomes. Traditional therapies often fail to effectively eradicate E. faecalis. In this study, we develop a novel nanozyme, LysPd138@ZIF-8, by synthesizing a ZIF-8 framework and encapsulated a bacteriophage lysin specific to E. faecalis. This nanozyme exhibits excellent biocompatibility, targeted antibacterial activity, and sustained drug release. Antibacterial assays demonstrate superior efficacy in eliminating E. faecalis, including biofilm-related bacteria. Alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining confirm that LysPd138@ZIF-8 promotes osteogenesis, while Quantitative PCR (qPCR) analysis show upregulation of osteogenesis-related genes in osteoblasts. Ex vivo tooth experiments further validate its antibacterial efficacy against E. faecalis within complex dental structures. In a mouse model of apical periodontitis, treatment with LysPd138@ZIF-8 effectively clear E. faecalis from the pulp, reduce bone resorption as observed via CT imaging, and significantly inhibit periapical inflammation as evidenced by histological staining. In conclusion, LysPd138@ZIF-8 represents a promising therapeutic strategy for refractory apical periodontitis, combining potent antibacterial efficacy against E. faecalis with osteogenic properties for enhanced clinical management of this challenging condition.