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AimTo create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis.MethodologyThe Gene Expression Omnibus (GEO) database, an international public repository of genomics data sets, was searched for human microarray datasets assessing pulpitis. An irreversible pulpitis gene expression signature was generated by differential expression analysis. The statistically significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. qPCR was used to validate novel pulpitis genes. An ex vivo pulpitis model was used to test the effects of the compounds identified, and the level of inflammatory cytokines was measured with qPCR, ELISA and multiplex array. Means were compared using the t-test or ANOVA with the level of significance set at p ≤ .05.ResultsPulpitis gene signatures were created using differential gene expression analysis at cutoff points p = .0001 and .000018. Top upregulated genes were selected as potential pulpitis biomarkers. Among these, IL8, IL6 and MMP9 were previously identified as pulpitis biomarkers. Novel upregulated genes, chemokine (C-C motif) ligand 21 (CCL21), metallothionein 1H (MT1H) and aquaporin 9 (AQP9) were validated in the pulp tissue of teeth clinically diagnosed with irreversible pulpitis using qPCR. ssCMap analysis identified fluvastatin (Statin) and dequalinium chloride (Quaternary ammonium) as compounds with the strongest correlation to the gene signatures (p = .0001). Fluvastatin reduced IL8, IL6, CCL21, AQP9 (p < .001) and MMP9 (p < .05) in the ex vivo pulpitis model, while dequalinium chloride reduced AQP9 (p < .001) but had no significant effect on the other biomarkers.ConclusionsAQP9, MT1H and CCL21 were identified and validated as novel biomarkers for pulpitis. Fluvastatin and dequalinium chloride identified by the ssCMap as potential therapeutics for pulpitis reduced selected pulpitis biomarkers in an ex vivo pulpitis model. In vivo testing of these licenced drugs is warranted.

International audience; The balance between periapical tissue inflammation and regeneration is pivotal in determining the success of endodontic treatment. This study was designed to investigate the effect of silicate-based root canal sealer BioRoot™ RCS (BRCS) on modulating the inflammatory response and early steps of regeneration initiated by human periodontal ligament (PDL) fibroblasts. Methods: Samples of BRCS and Pulp Canal Sealer (PCS) were incubated in culture medium to obtain material extracts. To simulate bacterial infection and endodontic sealer use, PDL fibroblasts were stimulated with lipopolysaccharides (LPS) and cultured with material extracts. Secretion of pro-inflammatory cytokine (IL-6) and growth factor (TGF-β1) were quantified by ELISA. Adhesion of inflammatory (THP-1) to endothelial cells (HUVEC) was studied using fluorescent THP-1, their migration using Boyden chambers and their activation using a cell adhesion assay. Proliferation of PDL fibroblasts was quantified by MTT assay. PDL stem cell migration was investigated using Boyden Chambers after immunofluorescence and RT-PCR characterization. Results: IL-6 secretion decreased with BRCS while it increased with PCS. TGF-β1 secretion significantly increased only with BRCS. The material extracts did not affect THP-1 adhesion to HUVECs but only BRCS inhibited their migration. Moreover, activation of THP-1 decreased with BRCS and to a lesser extent with PCS. Finally, BRCS increased PDL fibroblast proliferation without affecting PDL stem cell migration. By contrast, PCS decreased PDL cell proliferation and migration. Conclusions: These results report that the endodontic sealers inflammatory and regeneration modulation can be predicted in vitro. It demonstrates that BRCS, unlike PCS, has an anti-inflammatory effect and promotes regeneration.

Dental Mesenchymal Stem Cells (MSCs), including Dental Pulp Stem Cells (DPSCs), Stem Cells from Human Exfoliated Deciduous teeth (SHED), and Stem Cells From Apical Papilla (SCAP), have been extensively studied using highly sophisticated in vitro and in vivo systems, yielding substantially improved understanding of their intriguing biological properties. Their capacity to reconstitute various dental and nondental tissues and the inherent angiogenic, neurogenic, and immunomodulatory properties of their secretome have been a subject of meticulous and costly research by various groups over the past decade. Key milestone achievements have exemplified their clinical utility in Regenerative Dentistry, as surrogate therapeutic modules for conventional biomaterial-based approaches, offering regeneration of damaged oral tissues instead of simply “filling the gaps.” Thus, the essential next step to validate these immense advances is the implementation of well-designed clinical trials paving the way for exploiting these fascinating research achievements for patient well-being: the ultimate aim of this ground breaking technology. This review paper presents a concise overview of the major biological properties of the human dental MSCs, critical for the translational pathway “from bench to clinic.”

International audience; Purpose: 1) To evaluate the marginal sealing efficacy of Biodentine at the cervical margins of approximal cavities placed in molars; 2) to evaluate and compare the use of Biodentine in combination with resin-based adhesives and a resin composite, compared with a resin-modified glass-ionomer cement (Fuji II LC).Materials and Methods: Sixty approximal cavities were prepared on mesial and distal surfaces of 30 extracted human third molars. The teeth were randomly assigned into 6 groups of 10 cavities each: (G1) Biodentine, (G2) Fuji II LC as a filling material, (G3) Biodentine as a base + Optibond Solo Plus + silane + Filtek Z250, (G4) as in G3 without silane, (G5) Biodentine as a base + Septobond SE + Filtek Z250, (G6) Fuji II LC as a base + Optibond Solo Plus + Filtek Z250. The materials were applied according to the manufacturers' instructions. Biodentine required no dentin or enamel surface conditioning treatment. The teeth were thermocycled 2500x (5°C to 55°C). The specimens were then sealed with a 1-mm window around the marginal interface. Samples were immersed in a 50% w/v silver nitrate solution and exposed to a photodeveloping solution. The teeth were embedded in resin (Sody 33) and sectioned through the restorations. The silver penetration was directly measured using a light microscope. The results were expressed as ordinal scores from 0 to 3 at cervical, interfacial, and enamel margins. The data were analyzed with the nonparametric Kruskal-Wallis, Games Howell, and Wilcoxon signed rank tests (p < 0.05).Results: No statistically significant differences were found between the 6 groups, neither for the dentin cervical margins nor for cervical lining (Biodentine or Fuji II LC)/resin composite interfaces. Statistically significant differences were observed between G5 (median score = 2.0) and the other groups (median score = 1.0) for the enamel margins. Statistically significant differences were found between enamel and dentin cervical margins in G2 (enamel median score = 1.0; dentin median score = 1.5) and G5 (enamel median score = 2.0; dentin median score = 1.0).Conclusion: Within the limits of this in vitro study, Biodentine as dentin substitute in cervical lining restorations or as a restorative material in approximal cavities when the cervical extent is under the CEJ seems to perform well without any conditioning treatment. However, the operating time is longer than when a RMGIC (Fuji II LC) is used.

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Objectives Starting in 2020 pandemic of Covid-19 has made an impact on everyday clinical work and consequently medication prescribing for dental practitioners. During a 2-year time, measures have been modified, depending on each country's government decisions. In Croatia in 2020 stringency index was strong, while in 2021 index was very weak and in spring 2022 restriction measures were suspended. We investigated the impact of the pandemic and restriction measures on the dental prescribing pattern. Methods Data related to prescription practice were delivered by the Croatian Health Insurance Institute for the years of 2019. - 2021. The number of dentists’ prescriptions, the cost of medicines, and the number of packages prescribed have been included in the analysis. Results Changes in prescription patterns that could be attributed to the restriction's measures were seen in the results of this study in analgesic and antiseptic prescriptions. For the most of medications from these groups, the rise was great only while the measures were strict in the first year, while in the second year of the pandemic the increase significantly dropped. An exception from this behavior is seen for the ibuprofen, whose utilization is showing a continuous increase for the observed time period as well as for the 5 previous years. The most prescribed medications were antibiotics with no significant changes in their prescribing pattern for the pandemic period. Wide spectrum antibiotics utilization is showing a slow but continuous increase while narrow spectrum is in decrease. Pandemic has made an impact only on prescribing of azithromycin, whose utilization increased between years for 39, 4%, and 8, 7% respectively. The reason for this anomaly is to be investigated. Conclusions Restricted access to dental care due to COVID-19 resulted in changes to the prescription pattern of dental medications. The changes that could be attributed to the restriction measures are seen in pain relief medications, antiseptics, and wide-spectrum antibiotic azithromycin. Adaptation to the Covid- 19 pandemic setting in dentistry is now over, and observed abnormalities have to be corrected primarily through evidence-based dental prescribing protocols and guidelines, in order to ensure rationality in medication prescribing and good clinical practice.

Objectives To investigate the pulpal repair potential of an experimental zirconium-oxide containing tricalcium-silicate cement, referred to as ‘TCS 50’. Materials and methods The effect of TCS 50 on viability, proliferation, migration, and odontoblastic differentiation of human dental pulp cells (HDPCs) was assessed using XTT assay, in-vitro wound healing assay and RT-PCR, respectively. Additionally, the pulp-capping potential was evaluated using a vital human tooth model. Statistical analysis was performed using non-parametric Kruskal-Wallis test and post-hoc test (Mann-Whitney U test). The tests were performed at a significance level of α = 0.05. Results The effect of TCS 50 towards HDPCs was dose dependent. Undiluted TCS 50 extract showed no immediate adverse impact on cell viability (p > .05); however, it significantly inhibited proliferation and migration of HDPCs (p < .05). A 25% diluted TCS 50 extract showed no significant effect on cell viability, proliferation or migration (p > .05), and it significantly enhanced odontoblastic differentiation of HDPCs (p < .05). In pulps capped with TCS 50 for both 2 and 4 weeks, H&E staining revealed a normal morphology of pulp tissue; mineralized foci with cellular components entrapped in the matrix were formed underneath the exposure site. Collagen I expression was weak within the matrix of mineralized foci, while the expression of nestin was positive for entrapped cellular components within the mineralized foci, indicating that the formed mineralized foci corresponded to an initial form of reparative dentin formation. Conclusion TCS 50 is capable of generating an early pulp-healing reaction and therefore could serve as a promising pulp-capping agent. ispartof: Materials Science & Engineering C-Materials For Biological Applications vol:116 ispartof: location:Netherlands status: Published online