Diabetes-associated periodontitis (DP) aggravates diabetic complications and increases mortality from diabetes. DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult. In this study, we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to DP. Moreover, inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal inflammation. Furthermore, bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic periodontium. This finding provides a basis for the development of an effective therapeutic approach for treating DP.

Metformin is an old and widely accepted first-line drug for treating type 2 diabetes. Our previous studies demonstrate that metformin can stimulate the osteo/odontogenic differentiation of human-induced pluripotent stem cell-derived mesenchymal stem cells and human dental pulp cells (DPCs). Due to the rapid dilution of metformin from the defect area, the aim of this study was to develop a drug delivery system with controlled release of metformin to promote cell viability and odontogenic differentiation of DPCs favoring dentin regeneration. Calcium phosphate cement (CPC) containing chitosan and metformin as a scaffold was synthesized. DPCs were seeded onto the scaffold, and the viability and proliferation were evaluated at several time points. For osteogenic differentiation analysis, alkaline phosphatase (ALP) activity was tested, cells were stained with Alizarin Red, and the expression of odontogenic markers was evaluated by real-time polymerase chain reaction. DPCs remained viable and attached well to the CPC-chitosan composite scaffold. Moreover, the addition of metformin to the CPC-chitosan composite did not adversely affect cell proliferation, compared to that of CPC control. Our data further revealed that the novel CPC-chitosan-metformin composite enhanced the odontogenic differentiation of DPCs, as evidenced by higher ALP activity, elevated expression of odontoblastic markers, and strong mineral deposition. These results suggest that the new CPC-chitosan-metformin composite is a highly promising scaffold with the potential for tissue engineering applications including dentin regeneration.

Apical periodontitis (AP) is a chronic infection of endodontic origin accompanied with bone destruction around the apical region. Semaphorin3A (Sema3A) and neuropilin-1 (Nrp1) are regarded as a pair of immune regulators in bone metabolism. In this study, we firstly investigated the expression pattern of Sema3A/Nrp1 in apical periodontitis and its correlation with bone destruction. Using rat animal model, we analysed the level of mandibular bone destruction and the expression of Sema3A/Nrp1 on days 0, 7, 14, 21, 28, and 35 after pulp exposure. In addition, clinical samples from apical periodontitis patients were obtained to analyse the expression of Sema3A/Nrp1. These results indicated that the bone destruction level expanded from days 7 to 35. The number of positive cells and level of mRNA expression of Sema3A/Nrp1 were significantly decreased from days 7 to 35, with a negative correlation with bone destruction. Moreover, expression of Sema3A/Nrp1 in the AP group was reduced compared to the control group of clinical samples. In conclusion, decreased expression of Sema3A/Nrp1 was observed in periapical lesions and is potentially involved in the bone resorption of the periapical area, suggesting that Sema3A/Nrp1 may contribute to the pathological development of apical periodontitis.

Demineralized dentin matrix (DDM), derived from human teeth, is an excellent scaffold material with exciting bioactive properties to enhance bone and dental tissue engineering efficacy. In this article, first the nano-structure and bioactive components of the dentin matrix were reviewed. Then the preparation methods of DDM and the resulting properties were discussed. Next, the efficacy of DDM as a bone substitute with in vitro and in vivo properties were analyzed. In addition, the applications of DDM in tooth regeneration with promising results were described, and the drawbacks and future research needs were also discussed. With the extraction of growth factors from DDM and the nano-structural properties of DDM, previous studies also broadened the use of DDM as a bioactive carrier for growth factor delivery. In addition, due to its excellent physical and biological properties, DDM was also investigated for incorporation into other biomaterials design and fabrication, yielding great enhancements in hard tissue regeneration efficacy.