Mesenchymal stem cell-derived extracellular vesicles for treatment of bone loss within periodontitis in pre-clinical animal models: a meta-analysis.

BACKGROUND: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent an effective and promising strategy for periodontitis, although studies remain pre-clinical. Herein, a meta-analysis was conducted to assess the efficacy of MSC-EVs in animal models of periodontitis. METHODS: The PubMed, Web of Science, and Embase electronic databases were searched up to Dec 2022 to retrieve preclinical studies examining the use of MSC-EVs for periodontitis treatment. Meta-analyses and sub-group analyses were performed to assess the effect of MSC-EVs on Bone Volume/Total Volume (BV/TV) or the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) in pre-clinical animal models of periodontitis. RESULTS: 11 studies published from Mar 2019 to Oct 2022 met the inclusion criteria. Overall, MSC-EVs contributed to periodontal bone regeneration in the inflammatory bone loss area due to periodontitis, as represented by a weighted mean difference (WMD) of 14.07% (95% CI = 6.73, 21.41%, p < 0.001) for BV/TV and a WMD of -0.12 mm (95% CI= -0.14, -0.11 mm, p < 0.001) for CEJ-ABC. However, sub-analysis suggested that there was no significant difference in CEJ-ABC between studies with bioactive scaffolds and studies without bioactive scaffolds (p = 0.60). CONCLUSIONS: The present study suggests that MSC-EVs may represent an attractive therapy for the treatment of inflammatory bone loss within periodontitis.

Comparison of crown fit and operator preferences between tooth preparation with electric and air-turbine handpieces.

STATEMENT OF PROBLEM: Tooth preparations for ceramic crowns require precision and accuracy, which may be influenced by the choice of dental handpiece. However, comparisons of the accuracy of tooth preparations made with traditional air-turbine handpieces and electric handpieces are lacking. PURPOSE: The purpose of this in vitro study was to evaluate operator preferences and tooth preparation performance by using electric and air-turbine handpieces with self-reported preferences, sound levels, surface roughness, and the fit of the crown produced. MATERIAL AND METHODS: Twenty dentists were asked to use the air-turbine or the electric handpiece. Feedback on the noise, weight, feel of grip, flexibility, and tooth preparation in general was scored according to a visual analog scale (VAS). Additionally, the dentists were asked to complete a questionnaire on their handpiece preference. The noise of the 2 handpieces was measured by using a precision sound level meter. The surface roughness of 10 teeth was measured by using a profilometer. The other 18 teeth were prepared to measure the marginal and internal fit of ceramic crowns by the replica technique. The VAS scores of operator preferences were analyzed with the Wilcoxon signed ranks test. Decibel levels were analyzed with the Mann-Whitney U test. The McNemar test was used to compare the ratio of preferred handpiece. The surface roughness and marginal and internal fit were analyzed with the independent t test to determine significant differences (all α=.05). RESULTS: The electric handpiece was heavier, had a poorer grip feel, was less flexible (P<.001), produced lower noise and better feeling of the tooth preparation in general (P<.001), and was preferred in the finishing stage for its greater smoothness (P<.05). The noise produced by the electric handpiece was lower during both idling and tooth preparation at 15-cm, 30-cm, and 45-cm distances (P<.01). The electric handpiece produced surface roughness values (Sa) similar to those of the air-turbine handpiece (P>.05). No significant differences were noted for the marginal and internal crown fit between the air-turbine handpiece and electric handpiece groups (P>.05). CONCLUSIONS: Despite its heavier weight, poorer grip feel, and less flexibility, the electric handpiece emitted lower noise, produced better feeling of the tooth preparation in general, and was preferred in the finishing step of tooth preparation for its greater smoothness than the air-turbine handpiece. The surface roughness of the prepared teeth and the crown fit between the tooth and ceramic crown were not affected by the air-turbine or electric handpiece.

Knowledge of Infection Prevention and Attitudes Towards HIV/AIDS Among Chinese Dental Bachelor Interns: An Appeal for Educational Intervention.

PURPOSE: The present study aimed to assess the current situation of Chinese dental bachelor interns on HIV/AIDS-related knowledge and their attitudes towards HIV/AIDS patients. MATERIALS AND METHODS: A cross-sectional, paper-based survey involving 147 dental students from three Chinese dental schools was conducted. Students were recruited to complete the questionnaire regarding their knowledge, awareness and attitudes concerning HIV/AIDS anonymously and voluntarily. RESULTS: A total of 144 students responded to the study, generating a response rate of 98.0%. Although 97.0% of the dental students believed dentists were at high risk of HIV infection, 97.2% of students expressed no prejudice towards HIV/AIDS patients and stated their willingness to provide oral healthcare service for such patients. No statistically significant differences in the responses on attitudes and some basic knowledge were found between students who had received the relevant education about infection control and the students who had not. However, regarding most questions about oral manifestations in adult and paediatric patients living with AIDS, the students who received relevant education showed more knowledge than the students who did not (p <0.05). The cognitive level about respecting HIV/AIDS patients' autonomy and privacy was generally low in all the students. CONCLUSIONS: Most of the dental students in this survey held positive attitudes towards HIV/AIDS patients and good grasp of some basic knowledge about HIV/AIDS. On the other hand, the questionnaire results reflected gaps in education, such as respecting HIV/AIDS patients' privacy.

[Influence of preparation height and cement space on the fit and retention of computer aided design/computer aided manufacturing zirconia crown].

OBJECTIVE: To investigate the effects of preparation height and cement space on the fit and retention of computer aided design (CAD)/computer aided manufacturing (CAM) zirconia crown, and to provide reference for the clinical design and fabrication of CAD/CAM crowns. METHODS: 3D printing system was used to fabricate resin abutment teeth with convergence angle of 2° and height of 1-3 mm. The models' optical impressions were collected by the three-shape scanner. Then, the cement spaces were set by Cradle CAD/CAM system at 10-50 µm to create an all-ceramic zirconia crown. The fit of the crowns was measured by using silicone rubber interstitial impression method. The retention of the crowns was measured by pull-off test with uniaxial tensile force after the crown was bonded. The data were analyzed by SPSS 22.0 soft-ware. RESULTS: When the preparation height was fixed, the fitness values of different cement space groups have statistical difference (P<0.05), whereas the retention values of different cement space groups have no statistical difference (P>0.05). The fitness values of different preparation height groups have no statistical difference (P>0.05), and the retention values of different preparation height groups have statistical difference (P<0.05) when the cement space was fixed. No interaction was observed between the cement space and the preparation height (P>0.05). CONCLUSIONS: When cradle CAD/CAM system is used to create a full crown in the clinic, the preparation height should be set to more than 3 mm, and the cement space should be set at 30 µm.

Contribution of Mitophagy to Cell-Mediated Mineralization: Revisiting a 50-Year-Old Conundrum.

Biomineralization in vertebrates is initiated via amorphous calcium phosphate (ACP) precursors. These precursors infiltrate the extracellular collagen matrix where they undergo phase transformation into intrafibrillar carbonated apatite. Although it is well established that ACP precursors are released from intracellular vesicles through exocytosis, an unsolved enigma in this cell-mediated mineralization process is how ACP precursors, initially produced in the mitochondria, are translocated to the intracellular vesicles. The present study proposes that mitophagy provides the mechanism for transfer of ACP precursors from the dysfunctioned mitochondria to autophagosomes, which, upon fusion with lysosomes, become autolysosomes where the mitochondrial ACP precursors coalesce to form larger intravesicular granules, prior to their release into the extracellular matrix. Apart from endowing the mitochondria with the function of ACP delivery through mitophagy, the present results indicate that mitophagy, triggered upon intramitochondrial ACP accumulation in osteogenic lineage-committed mesenchymal stem cells, participates in the biomineralization process through the BMP/Smad signaling pathway.

Biodegradable mesoporous delivery system for biomineralization precursors.

Scaffold supplements such as nanoparticles, components of the extracellular matrix, or growth factors have been incorporated in conventional scaffold materials to produce smart scaffolds for tissue engineering of damaged hard tissues. Due to increasing concerns on the clinical side effects of using large doses of recombinant bone-morphogenetic protein-2 in bone surgery, it is desirable to develop an alternative nanoscale scaffold supplement that is not only osteoinductive, but is also multifunctional in that it can perform other significant bone regenerative roles apart from stimulation of osteogenic differentiation. Because both amorphous calcium phosphate (ACP) and silica are osteoinductive, a biodegradable, nonfunctionalized, expanded-pore mesoporous silica nanoparticle carrier was developed for loading, storage, and sustained release of a novel, biosilicification-inspired, polyamine-stabilized liquid precursor phase of ACP for collagen biomineralization and for release of orthosilicic acid, both of which are conducive to bone growth. Positively charged poly(allylamine)-stabilized ACP (PAH-ACP) could be effectively loaded and released from nonfunctionalized expanded-pore mesoporous silica nanoparticles (pMSN). The PAH-ACP released from loaded pMSN still retained its ability to infiltrate and mineralize collagen fibrils. Complete degradation of pMSN occurred following unloading of their PAH-ACP cargo. Because PAH-ACP loaded pMSN possesses relatively low cytotoxicity to human bone marrow-derived mesenchymal stem cells, these nanoparticles may be blended with any osteoconductive scaffold with macro- and microporosities as a versatile scaffold supplement to enhance bone regeneration.

Mineralogenic characteristics of osteogenic lineage-committed human dental pulp stem cells following their exposure to a discoloration-free calcium aluminosilicate cement.

OBJECTIVES: An experimental discoloration-free calcium aluminosilicate cement has been developed with the intention of maximizing the beneficial attributes of tricalcium silicate cements and calcium aluminate cements. The present study examined the effects of this experimental cement (Quick-Set2) on the mineralogenic characteristics of osteogenic lineage-committed human dental pulp stem cells (hDPSCs), by comparing the cellular responses with a commercially available tricalcium silicate cement (white mineral trioxide aggregate (ProRoot(®) MTA); WMTA). METHODS: The osteogenic potential of hDPSCs exposed to the cements was examined using qRT-PCR for osteogenic gene expressions, Western blot for osteogenic-related protein expressions, alkaline phosphatase enzyme activity, Alizarin red S staining, Fourier transform infrared spectroscopy and transmission electron microscopy of extracellular calcium deposits. RESULTS: Results of the six assays indicated that osteogenic differentiation of hDPSCs was significantly enhanced after exposure to the tricalcium silicate cement or the experimental calcium aluminosilicate cement, with the former demonstrating better mineralogenic stimulation capacity. SIGNIFICANCE: The better osteogenic stimulating effect of the tricalcium silicate cement on hDPSCs may be due to its relatively higher silicate content, or higher OH(-) and Ca(2+) release. Further investigations with the use of in vivo animal models are required to validate the potential augmenting osteogenic effects of the experimental discoloration-free calcium aluminosilicate cement.

Revival of nitrogen-containing bisphosphonate-induced inhibition of osteoclastogenesis and osteoclast function by water-soluble microfibrous borate glass.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious skeletal complication associated with the long-term oral or intravenous use of nitrogen-containing bisphosphonates (N-BPs). Here, we investigated the effects of an ionic cocktail prepared from water-soluble microfibrous borate glass on neutralizing the inhibitory effects of two heterocyclic N-BPs, risedronate or zoledronic acid, on osteoclastogenesis, apoptosis of differentiated osteoclasts and osteoclast function. Cell growth and proliferation assays were first performed on RAW 264.7 cells to optimize the concentrations of the ionic cocktail and N-BPs to be used for static cell culture. The pre-osteoclasts were then stimulated with RANKL to differentiate into osteoclasts. The effects of the ionic cocktail and N-BPs on osteoclast differentiation, apoptosis and function were subsequently examined using 3 series of experiments conducted at the gene, protein, morphological and functional levels. After concentration optimization, the ionic cocktail was found to partially reverse N-BP-induced inhibition of osteoclastogenesis, stimulation of osteoclasts apoptosis and reduction of osteoclast resorptive activity. Ultrastructural examination of osteoclasts that had been exposed to either N-BP identified classical features of late apoptosis and secondary necrosis, while osteoclasts exposed simultaneously to the concentration-optimized ionic cocktail and N-BPs exhibited only signs of early apoptosis that were possibly reversible. Taken together, the results of the 4 series of experiments indicate that the ionic cocktail produced from dissolution of borate glass dressings has the potential to rescue the adverse effects of heterocyclic N-BPs on osteoclast differentiation and function. These results warrant further confirmation using dynamic cell culture and small animal BRONJ models. STATEMENT OF SIGNIFICANCE: Long-term oral and intravenous use of nitrogen-containing bisphosphonates (N-BPs) may result in bisphosphonate-related osteonecrosis of the jaw (BRONJ) due to the suppression of normal bone turnover. There is no effective treatment for such a complication to date. This work reported the use of an ionic cocktail derived from water-soluble microfibrous borate glass to revert heterocyclic N-BP-induced inhibition of osteoclastogenesis, stimulation of osteoclasts apoptosis and reduction of osteoclasts resorption in static cell culture condition. This ionic cocktail may have the potential to be further developed into a new adjunctive treatment for BRONJ.

Cytotoxicity and osteogenic potential of silicate calcium cements as potential protective materials for pulpal revascularization.

OBJECTIVES: In pulpal revascularization, a protective material is placed coronal to the blood clot to prevent recontamination and to facilitate osteogenic differentiation of mesenchymal stem cells to produce new dental tissues. Although mineral trioxide aggregate (MTA) has been the material of choice for clot protection, it is easily displaced into the clot during condensation. The present study evaluated the effects of recently introduced calcium silicate cements (Biodentine and TheraCal LC) on the viability and osteogenic differentiation of human dental pulp stem cells (hDPSCs) by comparing with MTA Angelus. METHODS: Cell viability was assessed using XTT assay and flow cytometry. The osteogenic potential of hDPSCs exposed to calcium silicate cements was examined using qRT-PCR for osteogenic gene expressions, alkaline phosphatase enzyme activity, Alizarin red S staining and transmission electron microscopy of extracellular calcium deposits. Parametric statistical methods were employed for analyses of significant difference among groups, with α=0.05. RESULTS: The cytotoxic effects of Biodentine and TheraCal LC on hDPSCs were time- and concentration-dependent. Osteogenic differentiation of hDPSCs was enhanced after exposure to Biodentine that was depleted of its cytotoxic components. This effect was less readily observed in hDPSCs exposed to TheraCal LC, although both cements supported extracellular mineralization better than the positive control (zinc oxide-eugenol-based cement). SIGNIFICANCE: A favorable tissue response is anticipated to occur with the use of Biodentine as a blood clot-protecting material for pulpal revascularization. Further investigations with the use of in vivo animal models are required to validate the potential adverse biological effects of TheraCal LC on hDPSCs.

[Effect of a desensitizing polishing paste on bonding strength of two self-etching adhesives to dentin].

OBJECTIVE: To evaluate the effect of an 8% arginine-CaCO3 containing desensitizing polishing paste on bonding strength of two self-etching adhesives to dentin. METHODS: Thirty-six intact human premolars extracted for orthodontic reasons were collected within 1 month after extraction and randomly assigned into three groups using a table of random numbers (n = 12): specimens without any treatment served as control. In the polishing powder group specimens were polished with a slurry of pumice, and in the desensitizing polishing paste group dentin surfaces of the sample teeth were treated with 8% arginine-CaCO3 containing desensitizing polishing paste. Then each group was divided into two sub-groups using a table of random numbers in order to evaluate the bonding strength of two self-etching adhesive agents (G-Bond, GC; Fl-Bond II, Shofu). Microtensile bond strength test was conducted immediately and after 5000 thermocycling (n = 15). Scanning electron microscope (SEM) was used to evaluate the occluding effect of the desensitizing polishing paste. RESULTS: In the pre-thermocycling stage, there were no significant differences in Fl-Bond II bonding strength among the three groups [control: (30.34 ± 5.42) MPa, polishing powder group: (29.72 ± 5.16) MPa, desensitizing polishing paste group: (31.53 ± 4.86) MPa] (P > 0.05). However there were significant differences among the three groups in G-Bond bonding strength [control: (38.19 ± 4.42) MPa, polishing powder group: (36.47 ± 4.72) MPa, desensitizing polishing paste group: (46.88 ± 7.83) MPa] (P < 0.05). After thermocycling process, there were no significant differences in bonding strength among the three groups in both G-Bond groups and Fl-Bond II groups. SEM observation showed that the desensitizing polishing paste could occlude open dentinal tubules effectively, and the application of self-etching adhesives could re-open the dentinal tubular orifices. An even layer can be seen on the dentin surface treated with self-etching adhesive containing functional monomers. CONCLUSIONS: The 8% arginine-CaCO3 containing desensitizing polishing paste could effectively occlude dentinal tubules, thus may have potential benefits in preventing post-operative sensitivity. Additionally, it had no adverse effect on bonding strength of self-etching adhesives to dentin.

[Study on the micropermeability of resin-dentin bonding interfaces with ethanol-wet bonding technique].

OBJECTIVE: To evaluate the micropermeability on bonding hydrophobic adhesive to dentin with ethanol-wet bonding under simulated pulp pressure. METHODS: Twenty-four intact human third molars were used in the study. After the enamel of occlusal surfaces was removed, the molars were randomly divided into six groups. Adper Scotchbond Multi-Purpose was used in the control group; in the experimental groups, the dentin surfaces were saturated with ethanol for 20 s (group 1), 1 min (group 2), 2 min (group 3), 3 min (group 4) or with a series of increasing ethanol concentrations before application of hydrophobic adhesive (group 5). All the bonding procedures were done under simulated pulp pressure. After 24 hours, micro-tensile bond strength test were performed on the specimens. Bonding interfaces were observed under laser scanning confocal microscope (LSCM) after the pulp chamber were filled with a water-soluble fluoroprobe rhodamine B for 3 hours. RESULTS: Compared with the control group [(38.14 ± 4.97) MPa], bond strengths in group 1 [(21.02 ± 7.23) MPa] and group 2 [(29.64 ± 3.81) MPa] were statistically lower (P > 0.05), while bond strength in group 3 [(38.40 ± 5.03) MPa], group 4 [(37.26 ± 4.68) MPa] and group 5 [(40.12 ± 5.95) MPa] were similar to the control group (P < 0.05). The images taken by LSCM showed that with extension of ethanol-wet time, the deposition of fluorescent dye in hybrid layer and along the dentinal tubules decreased gradually. Especially in group 5, only spare fluorescent dye deposition could be detected in the hybrid layer. CONCLUSIONS: Dentin saturated with ethanol for more than 2 min before bonding hydrophobic adhesive to dentin could provide favorable bond strength and decreased the micropermeability of bonding interfaces under simulated pulp pressure.

Effects of ethanol-wet bonding technique on root dentine adhesion.

OBJECTIVE: To investigate the effects of ethanol-wet bonding on the adhesion of experimental hydrophobic and commercial hydrophilic adhesives to root dentine. METHODS: A total of 43 single-rooted integrated human premolars were selected and sectioned. Of the 86 initially obtained specimens, 66 were randomly and equally divided into water-wet bonding and ethanol-wet bonding groups (n = 33). The specimens of each group were subdivided into three subgroups (n = 11) based on different adhesives: two experimental hydrophobic adhesives (Bis-GMA/TEGDMA, BT; and UDMA/TEGDMA, UT) and one commercial hydrophilic adhesive (Adper™ Single Bond 2, SB). The root surfaces were ground, acid-etched and rinsed and resin composite applied. After storing in distilled water for 24 h at 37°C, the shear bond strength (SBS) of each specimen was measured. A sample from each subgroup was randomly selected and prepared for scanning electron microscopy (SEM) analysis. The remaining 20 specimens were used in the contact angle (CA) experiment, and the values of CA were measured. SBS was analysed with two-way ANOVA/Tukey's multiple comparison test and CA with independent sample t test. RESULTS: A significant increase in SBS to root dentine was observed in the ethanol-wet bonding group compared with the traditional water-wet bonding group. The experimental hydrophobic adhesives (UT group) with ethanol-wet bonding presented the highest SBS (22.44 ± 3.32 MPa). CA increased significantly after the dentine surfaces were dried, especially for the water-saturated group. CONCLUSION: The adhesion to root dentine surfaces with ethanol-wet bonding may be superior to water-wet bonding.