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

Zongshan Shen; Shuhong Kuang; Yong Zhang; Mingmei Yang; Wei Qin; Xuetao Shi; Zhengmei Lin

doi:10.1016/j.bioactmat.2020.07.002

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

Bioact Mater. 2020 Jul 16;5(4):1113-1126. doi: 10.1016/j.bioactmat.2020.07.002. eCollection 2020 Dec.

Authors

Zongshan Shen¹, Shuhong Kuang¹, Yong Zhang¹, Mingmei Yang¹, Wei Qin¹, Xuetao Shi², Zhengmei Lin¹

Affiliations

¹ Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
² National Engineering Research Centre for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, China.

Abstract

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.

Keywords: Chitosan hydrogel; Dental pulp stem cells; Exosomes; Macrophages; Periodontitis.