Maresin 1 Resolves Inflammation and Aids Bone Healing in Periapical Lesions

Chronic apical periodontitis (CAP) is a persistent inflammatory condition caused by microbial infections in the root canal system, leading to bone loss and tissue damage. In this study, we tested the hypothesis that maresin 1 (MaR1), a specialized proresolving mediator, facilitates inflammatory resolution and promotes bone healing in CAP. We developed a CAP model in mice through pulp exposure. Animals received intracanal administration of either MaR1 or a vehicle. Micro-computed tomography (micro-CT) was used to analyze lesion size and bone volume changes. Inflammatory cell infiltration was assessed in hematoxylin and eosin-stained sections, and microbial diversity was analyzed using next-generation sequencing. The role of regulatory T cells (Tregs) was further explored through diphtheria toxin-induced depletion of Tregs in Foxp3eGFP/IL17 transgenic mice. All statistical analyses were performed using parametric methods, as confirmed by the Shapiro-Wilk test for data normality. Analysis of variance with Tukey's post hoc and Bonferroni-corrected t tests was applied. P < 0.05 was considered significant. In 2-dimensional analyses, a significant difference was observed between the control and lesion groups, supporting the validity of the experimental model. MaR1 treatment significantly reduced lesion size (P < 0.0001). The bone volume/total volume ratio was significantly higher in the MaR1 group than in the vehicle group (P < 0.05). Bone mass was reduced in the lesion group, whereas MaR1 treatment significantly alleviated this loss (P < 0.05). The number of inflammatory cells was significantly lower in the MaR1 group compared to the vehicle group (P < 0.05). MaR1 also reduced Enterococcus faecalis, a key pathogen in persistent infections. This study highlights MaR1 as a promising treatment for chronic apical periodontitis, showing benefits in resolving inflammation, preserving bone, and reducing E. faecalis. Unlike conventional therapies, MaR1 supports immune modulation and tissue repair.