Chitosan hydrogel incorporated with dental pulp stem cell-derived exosomes alleviates periodontitis in mice via a macrophage-dependent mechanism.

Periodontitis is caused by host immune-inflammatory response to bacterial insult. A high proportion of pro-inflammatory macrophages to anti-inflammatory macrophages leads to the pathogenesis of periodontitis. As stem cell-derived exosomes can modulate macrophage phenotype, dental pulp stem cell-derived exosomes (DPSC-Exo) can effectively treat periodontitis. In this study, we demonstrated that DPSC-Exo-incorporated chitosan hydrogel (DPSC-Exo/CS) can accelerate the healing of alveolar bone and the periodontal epithelium in mice with periodontitis. Gene Ontology (GO) term enrichment analysis showed that treatment with DPSC-Exo/CS ameliorated periodontal lesion by suppressing periodontal inflammation and modulating the immune response. Specifically, DPSC-Exo/CS facilitated macrophages to convert from a pro-inflammatory phenotype to an anti-inflammatory phenotype in the periodontium of mice with periodontitis, the mechanism of which could be associated with miR-1246 in DPSC-Exo. These results not only shed light on the therapeutic mechanism of DPSC-Exo/CS but also provide the basis for developing an effective therapeutic approach for periodontitis.