Periodontitis is a widespread disease characterized by inflammation‐induced progressive damage to the tooth‐supporting structures until tooth loss occurs. The regeneration of lost/damaged support tissue in the periodontium, including the alveolar bone, periodontal ligament, and cementum, is an ambitious purpose of periodontal regenerative therapy and might effectively reduce periodontitis‐caused tooth loss. The use of stem cells for periodontal regeneration is a hot field in translational research and an emerging potential treatment for periodontitis. This concise review summarizes the regenerative approaches using either culture‐expanded or host‐mobilized stem cells that are currently being investigated in the laboratory and with preclinical models for periodontal tissue regeneration and highlights the most recent evidence supporting their translational potential toward a widespread use in the clinic for combating highly prevalent periodontal disease. We conclude that in addition to in vitro cell‐biomaterial design and transplantation, the engineering of biomaterial devices to encourage the innate regenerative capabilities of the periodontium warrants further investigation. In comparison to cell‐based therapies, the use of biomaterials is comparatively simple and sufficiently reliable to support high levels of endogenous tissue regeneration. Thus, endogenous regenerative technology is a more economical and effective as well as safer method for the treatment of clinical patients. Stem Cells Translational Medicine 2019;8:392–403

Objective Although accumulating evidence indicates that macrophages are central players in the destructive and reparative phases of periodontal disease, their polarization states at different stages of periodontal inflammation remain unclear. Methods We collected gingival biopsies from patients with chronic periodontitis (P group), gingivitis (G group), or periodontally healthy individuals (H group). Polarized macrophages were identified through immunofluorescence. M1‐ and M2‐related cytokines were detected by immunohistochemistry. Results Compared with the H group, the P group had more M1 cells (higher M1/M2 ratio) and significantly higher TNF‐α, IFN‐γ, IL‐6, and IL‐12 levels. Although the G group also exhibited higher TNF‐α and IL‐12 levels than the H group, they had similar M1/M2 ratios. The M1/M2 ratio and IFN‐γ and IL‐6 levels were significantly higher in the P than the G group. Among M2‐related cytokines, IL‐4 levels were significantly higher in the G than the H group. The M1/M2 ratio was positively correlated with clinical probing depth (PD), and both were positively correlated with IFN‐γ and IL‐6. PD was negatively correlated with IL‐4. Conclusion Macrophage polarization in gingival tissue may be responsible for the development and progression of inflammation‐induced tissue destruction, and modulating macrophage function may be a potential strategy for periodontal disease management.

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Background: Although dental pulp stem cells (DPSCs) isolated from periodontally compromised teeth (P-DPSCs) have been demonstrated to retain pluripotency and regenerative potential, their use as therapeutics remains largely unexplored. In this study, we investigated the proangiogenic effects of extracellular vesicles (EVs) secreted by P-DPSCs using in vitro and in vivo testing models. Methods: Patient-matched DPSCs derived from periodontally healthy teeth (H-DPSCs) were used as the control for P-DPSCs. Conditioned media (CMs) derived from H-DPSCs and P-DPSCs (H-CM and P-CM), CMs derived from both cell types pretreated with the EV secretion blocker GW4869 (H-GW and P-GW), and EVs secreted by H-DPSCs and P-DPSCs (H-EVs and P-EVs) were prepared to test their proangiogenic effects on endothelial cells (ECs). Cell proliferation, migration, and tube formation were assessed using the Cell Counting Kit-8 (CCK-8), transwell/scratch wound healing, and Matrigel assays, respectively. Specifically, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analysis were used to examine the expression levels of angiogenesis-related genes/proteins in ECs in response to EV-based incubation. Finally, a full-thickness skin defect model was applied to test the effects of EVs on wound healing and new vessel formation.

The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes. First, faecal and salivary samples were collected from periodontally healthy participants (PH group, n = 16) and patients with severe periodontitis (SP group, n = 21) and analysed by 16S ribosomal RNA sequencing. Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups. Notably, more saliva-sourced microbes were observed in the faecal samples of the SP group. Then, the remaining salivary microbes were transplanted into C57BL6/J mice (the C-PH group and the C-SP group), and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group, with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group. In the colon, the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression. The mRNA expression levels of pro-inflammatory cytokines, chemokines and tight junction proteins were significantly higher in the C-SP group. To further investigate whether salivary bacteria could persist in the intestine, the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice. We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h. Thus, our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.