Polarized M2 macrophages induced by glycosylated nano‐hydroxyapatites activate bone regeneration in periodontitis therapy

Abstract Aim To investigate the association between periodontal macrophage polarization states and the alveolar bone levels, and to assess whether glycosylated nano‐hydroxyapatites (GHANPs) could improve bone regeneration in periodontitis by inducing macrophage M2 polarization. Materials and Methods The change of macrophage polarization state in inflammatory periodontal tissues (with bone loss) was examined using clinical gingival samples. The relationship between macrophage phenotype and bone level in periodontal bone loss and repair was evaluated using a mouse periodontitis model. The effect of GHANPs on macrophage polarization was assessed by the in vitro model of lipopolysaccharide (LPS)‐stimulated inflammation. The polarization‐related markers were detected by immunofluorescence staining, real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay analysis. The therapeutic effect of GHANPs on alveolar bone loss was explored in experimental periodontitis by histological staining and micro‐CT analysis. Results A lower macrophage M2/M1 ratio was observed in periodontitis‐affected human gingival tissues. The results of animal experiments demonstrated a positive correlation between a lower Arg‐1/iNOS ratio and accelerated alveolar bone loss; also, the proportion of Arg‐1‐positive macrophages increased during bone repair and regeneration. The administration of GHANPs partially restored M2 macrophage polarization after LPS stimulation. GHANPs increased alveolar bone repair and regeneration in experimental periodontitis induced by ligation, potentially related to their macrophage M2 transition regulation. Conclusions The findings of this study indicate that the induction of macrophage M2 polarization can be considered a viable approach for enhancing inflammatory bone repair. Additionally, GHANPs show potential in the clinical treatment of periodontitis.