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

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.

Mussel-inspired agarose hydrogel scaffolds for skin tissue engineering

“…Over the past decade, the use of hydrogel in wound dressing has been widely studied. Hydrogel dressings can create a moist wound environment that is beneficial for skin tissue regeneration [ 12 , 13 ]. Most of the reported hydrogel dressings are based on synthetic polymers and natural polymers (such as polysaccharide and protein) [ [14] , [15] , [16] , [17] ].…”

An overview of chitosan and its application in infectious diseases

“…Chitosan has adhesive properties and is used to treat periodontitis. A faster healing rate of alveolar bone and periodontal epithelium in mice with periodontitis was observed [ 71 ]. The vector system can be attached to the tooth surface, tongue surface, and buccal cavity mucosa.…”

Mesenchymal stem cell‐derived small extracellular vesicles as cell‐free therapy: Perspectives in periodontal regeneration

“…MSC sEV do not express cell surface major histocompatibility complex (MHC‐I and MHC‐II) proteins and thereby present advantages of low immunogenic response, unlike sEV derived from antigen‐presenting cells 7,33,34 …”

“…However, there is some heterogeneity in the studies. Some use conditioned medium and others use sEV (called exosomes in four studies, sEV in one), most of which are derived from human cells and come from a variety of tissues (bone marrow MSC, 18,35,40,48 adipose MSC, 13 dental MSC 23,31,34,39 ). Two teams use rat MSC 13,48 .…”

“…Two teams use rat MSC 13,48 . Six studies use a rat model of periodontitis, 13,18,31,35,39,48 two use the mouse model, 23,34 and one uses the dog model 40 . Only one study showed results at eight weeks, 48 the others did not go beyond four weeks.…”