Dentigerous cysts are one of the most prevalent types of odontogenic cysts and are associated with the crown of an unerupted tooth, especially of the mandibular third molar. In this study, the characteristics of a dentigerous cyst developed around a mandibular third molar on panoramic radiographs were investigated. The panoramic images of 257 consecutive dentigerous cyst cases associated with a mandibular third molar were analyzed. The mean age of the patients was 45.9 ± 13.3 years. The size of the cyst did not significantly correlate to the age of the patient. The unilocular type (89.1%) and the crown side type (68.5%) were significant. The associated mandibular third molars had a high frequency of class III (64.6%) and position B (48.3%) in Pell and Gregory classification and of horizontal position (36.3%) in angulation. Dentigerous cysts were thought to originate and grow commonly around deeply impacted third molars. The associated third molar with dentigerous cyst tends to have a mesial inclination. Dentigerous cysts do not appear to develop gradually after the crown formation has finished, but arise at various periods randomly.

Macrophages play an important role in the regulation of inflammation and immune response as well as the pathogenesis of chronic inflammatory diseases and cancer. Therefore, targeted delivery of therapeutic reagents to macrophages is an effective method for treatment and diagnosis. We previously examined the therapeutic applications of polyrotaxanes (PRXs) comprised of multiple cyclodextrins (CDs) threaded on a polymer chain and capped with bulky stopper molecules. In the present study, we designed an α-d-mannose-modified α-CD/poly(ethylene glycol)-based PRX (Man-PRX). The intracellular uptake of Man-PRX through the interaction with macrophage mannose receptor (MMR) in macrophage-like RAW264.7 cells was examined. Intracellular Man-PRX uptake was observed in MMR-positive RAW264.7 cells but was negligible in MMR-negative NIH/3T3 cells. In addition, the intracellular Man-PRX uptake in RAW264.7 cells was significantly inhibited in the presence of free α-d-mannose and an anti-MMR antibody, which suggests that MMR is involved in the intracellular uptake of Man-PRX. Moreover, the polarization of RAW264.7 cells affected the Man-PRX internalization efficiency. These results indicate that Man-PRX is an effective candidate for selective targeting of macrophages through a specific interaction with the MMR.

Bone morphogenetic protein 2 (BMP-2) has received considerable attention because of its osteoinductivity, but its use is limited owing to its instability and adverse effects. To reduce the dose of BMP-2, complexation with heparin is a promising approach, because heparin enhances the osteoinductivity of BMP-2. However, the clinical use of heparin is restricted because of its anticoagulant activity. Herein, to explore alternative polymers that show heparin-like activity, four polycarboxylates, poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), poly(aspartic acid) (PAsp), and poly(glutamic acid) (PGlu), were selected and their capability to modulate the osteoinductivity of BMP-2 was evaluated. Dynamic light scattering indicated that these polycarboxylates formed polyelectrolyte complexes with BMP-2. The osteogenic differentiation efficiency of MC3T3-E1 cells treated with the polycarboxylate/BMP-2 complexes was investigated in comparison to that of the heparin/BMP-2 complex. As a result, PGlu/BMP-2 complex showed the highest activity of alkaline phosphatase, which is an early-stage marker of osteogenic differentiation, and rapid mineralization. Based on these observations, PGlu could serve as an alternative to heparin in the regenerative therapy of bone using BMP-2.

Oral tissue regeneration has received growing attention for improving the quality of life of patients. Regeneration of oral tissues such as alveolar bone and widely defected bone has been extensively investigated, including regenerative treatment of oral tissues using therapeutic cells and growth factors. Additionally, small-molecule drugs that promote bone formation have been identified and tested as new regenerative treatment. However, treatments need to progress to realize successful regeneration of oral functions. In this review, we describe recent progress in development of regenerative treatment of oral tissues. In particular, we focus on cyclodextrin (CD)-based pharmaceutics and polyelectrolyte complexation of growth factors to enhance their solubility, stability, and bioactivity. CDs can encapsulate hydrophobic small-molecule drugs into their cavities, resulting in inclusion complexes. The inclusion complexation of osteoinductive small-molecule drugs improves solubility of the drugs in aqueous solutions and increases in vitro osteogenic differentiation efficiency. Additionally, various anionic polymers such as heparin and its mimetic polymers have been developed to improve stability and bioactivity of growth factors. These polymers protect growth factors from deactivation and degradation by complex formation through electrostatic interaction, leading to potentiation of bone formation ability. These approaches using an inclusion complex and polyelectrolyte complexes have great potential in the regeneration of oral tissues.

Kang J, et al. J Periodontal Implant Sci. 2023 Jun;53:e22. https://doi.org/10.5051/jpis.2204660233

Gene silencing of noggin by small interfering RNA (siRNA) is a promising approach for the treatment of bone defects, because noggin deactivates bone morphogenetic protein-2 (BMP-2) and suppresses osteogenic differentiation. Here, we demonstrated the silencing of the noggin gene by siRNA polyplexes composed of noggin-targeted siRNA and biocleavable cationic polyrotaxanes (DMAE-SS-PRX). To improve the endosomal escape efficiencies of the DMAE-SS-PRX/siRNA polyplexes, anionic and fusogenic GALA peptides were integrated onto the DMAE-SS-PRX/siRNA polyplexes via simple electrostatic interactions. The formation of ternary complexes was confirmed by gel electrophoresis, dynamic light scattering, and zeta-potential measurements. Although the association of GALA peptides with the DMAE-SS-PRX/siRNA polyplexes did not remarkably affect the cellular uptake efficiency of siRNA, the endosomal escape efficiency was remarkably increased for GALA/DMAE-SS-PRX/siRNA ternary polyplexes because of the endosomal and lysosomal membrane destabilization by GALA peptides. Consequently, GALA/DMAE-SS-PRX/siRNA ternary polyplexes showed significantly higher gene silencing efficiency against noggin and enhanced the BMP-2-mediated osteogenic differentiation efficiency. Therefore, we concluded that GALA/DMAE-SS-PRX/siRNA ternary polyplexes can be effective siRNA carriers for suppressing the expression of specific endogenous genes. Consequently, we believe that a more practical approach in vivo will be the combined use of BMP-2 and GALA/DMAE-SS-PRX/siRNA ternary polyplexes, because it will improve the efficacy of bone regeneration therapy.