Calcium phosphate cement (CPC) is promising for bone and dentin repair and regeneration. However, there has been no report of biphasic CPC for inducing dentin regeneration. The aim of this study was to develop a novel biphasic CPC containing β-tricalcium phosphate (β-TCP) and investigate its effects on odontogenic differentiation of human dental pulp stem cells (hDPSCs) and macrophage polarization. New biphasic CPC was formulated with different ratios of β-TCP to an equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA). Mechanical properties, biocompatibility, and odontogenic differentiation induction ability of the cements and the inflammatory reaction to the cements were examined. A series of CPC containing β-TCP was developed. CPC with 20% β-TCP exhibited homogeneity and injectability, an acceptable setting time, and a 2-fold increase in compressive strength. Significant increases in hDPSCs’ ALP activity, mineral deposit, DMP1 and DSPP gene and protein expressions were obtained for 20% TCP–CPC, compared with traditional CPC (p<0.01). The addition of β-TCP did not promote macrophage polarization to the pro-inflammation phenotype. The addition of 10% and 20% β-TCP promoted macrophage polarization to the anti-inflammatory phenotype. In conclusion, a biphasic β-TCP-modified CPC was developed for the first time, demonstrating substantially increased dentin regeneration capability, while promoting macrophages to an anti-inflammation phenotype. The novel biphasic CPC is promising for tooth tissue engineering and dentin regeneration applications.

The immune system plays an important role in the skeletal system during bone repair and regeneration. The controlled release of biological factors from the immune system could facilitate and optimize the bone remodeling process through the regulation of the activities of bone cells. This study aimed to determine the effect of the controlled delivery of immunomodulatory biologicals on bone regeneration. Immunostimulatory cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) and glucosylxanthone Mangiferin (MAG)-embedded microbeads were incubated with P. gingivalis-challenged splenocytes, or co-cultured with RAW264.7 cells. The effect of CpG ODN/MAG-containing microbeads on bone regeneration was then tested in vivo in a mouse alveolar bone defect model. The results demonstrated that MAG significantly antagonized P. gingivalis proliferation and reduced the live/dead cell ratio. After the addition of CpG ODN + MAG microbeads, anti-inflammatory cytokines IL-10 and IL-4 were upregulated on day 2 but not day 4, whereas pro-inflammatory cytokine IL-1β responses showed no difference at both timepoints. RANKL production by splenocytes and TRAP+ cell formation of RAW264.7 cells were inhibited by the addition of CpG ODN + MAG microbeads. Alveolar bony defects, filled with CpG ODN + MAG microbeads, showed significantly increased new bone after 4 weeks. In summary, this study evaluated a new hydrogel-based regimen for the local delivery and controlled release of biologicals to repair and regenerate alveolar bony defects. The combined CpG ODN + MAG treatment may promote alveolar bone regeneration through the anti-microbial/anti-inflammatory effects and the inhibition of RANKL-mediated osteoclastogenesis.

Introduction: To guide deep overbite treatment, the effectiveness of clear aligners and the influence of maxillofacial characteristics were assessed in levelling the curve of Spee (COS). Methods: Forty-two patients underwent phased treatment using clear aligners. Digital dental models were created before and after treatment following which predicted outcomes, and dental cast measurements were conducted in addition to the analysis of lateral cephalometric and panoramic radiographs. The anticipated COS correction was compared with the actual correction achieved. Using multiple linear regression, associations between levelling effectiveness and clinical indicators were evaluated to establish prediction equations. P = 0.05 indicated statistical significance. Results: The levelling effectiveness was 71.8 ± 19.0%. The regression model accounted for 88.5% of the variance in levelling effectiveness ( F -value = 167.209, adjusted R ² = 0.885, Akaike information criterion [AIC] [E]=-146.94). The levelling effectiveness was related to the vertical skeletal pattern, the angulation of the mandibular incisors to the mandibular plane, the axial inclination of the mandibular anterior teeth, and the pre-treatment COS depth. Levelling effectiveness and other maxillofacial variables were not significantly related. Conclusion: Clear aligners effectively level the COS. Patients with a larger Frankfort-mandibular plane angle, a pre-treatment COS depth, and an incisor-mandibular plane angle, more easily achieved COS levelling using clear aligners. Those with smaller mandibular incisor parallelism still achieved effective levelling.