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Objectives: The aim of this systematic review was to demonstrate the efficacy of topical application of corticosteroids in remineralization of dental pulp tissues to preserve their vitality and function., Data, Sources and Study Selection: An electronic search was performed using MEDLINE by PubMed, EMBASE, Web of Science (WOS), and Scopus databases. The inclusion criteria were in vitro studies that employed dental pulp tissue obtained from extracted healthy permanent human teeth and were subjected to topical administration of corticosteroids and evaluated tissue remineralization by performing any mineralization assay. A total of 11 studies were selected for inclusion. PRISMA guidelines were followed, and the methodological quality and risk of bias of the included studies were evaluated using the RoBDEMAT guidelines. Also, tables were designed for data extraction, including tissue mineralization and osteogenic differentiation as primary and secondary outcomes, respectively., Conclusions: Alizarin Red S (ARS) has been able to demonstrate a possible mineralizing power of corticosteroids, applied at an adequate dose. The up-regulation of Alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OSP), sialophosphoprotein (DSPP), runt-related transcription factor 2 (RUNX2), collagen type 1 alpha 1(COL1α1) and dentin matrix protein 1 (DMP-1) induced the osteogenic/odontogenic differentiation of dental pulp stem cells (DPSCs)., Clinical Significance: Deep carious lesions treatment is still challenging in restorative dentistry. Some treatments have been focused on dental pulp tissue remineralization to maintain the function and vitality. After corticosteroids topical application, mineral deposition and osteogenic differentiation have been detected., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Lipoteichoic acid from Lactobacillus plantarum (L. plantarum) is a significant virulence factor that exacerbates pulp inflammation. Lipoteichoic acid plays a role in modulating the inflammatory to proliferative phase transition is crucial in determining the outcome of pulp healing or necrosis. This study explores the role of L. plantarum on lymphocytes and the expression of transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor A (VEGF-A) in a male rat model of acute dental pulp injury., Design: The acute dental pulp model was created in the upper molar of Rattus novergicus using a round bur. Then, the dental pulp was exposed to 10 µg/ml of the lipoteichoic acid of L. plantarum and filled with a temporary filling. In the next 24, 48, and 72 h, each animal was decapitated, and the expression of TGF-β1 and VEGF-A in dental pulp was analyzed using indirect immunohistochemistry, while the lymphocytes analyzed using hematoxyline-eosin staining., Result: Lipoteichoic acid of L. plantarum induced acute dental pulp by increasing the lymphocyte number after 48 and 72 h of exposure (p < 0.05). While, inhibiting TGF-β1 expression after 48 and 72 h of exposure (p < 0.05), and VEGF-A was inhibiting after 72 h of exposure (p < 0.05)., Conclusion: Exposure to lipoteichoic acid from L. plantarum significantly accelerates the inflammatory response in the dental pulp. However, this accelerated inflammation disrupts the proliferative phase, potentially leading to more extensive damage to the dental pulp., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Tertiary lymphoid structure (TLS) is associated with various pathologies, including those of cancers and chronic infections. Depending on the organ, multiple factors regulate the formation of TLS. However, the role of TLS in immune response and the molecules that drive its formation remain uncertain. The dental pulp, includes a few immune cells surrounded by rigid mineralized tissue, and opens to the outside through the apical foramen. Owing to this special organization, the dental pulp generates a directional immune response to bacterial infection. Considering this aspect, the dental pulp is an ideal model for comprehensively studying the TLS. In the present study, single-cell RNA sequencing of healthy and inflamed human dental pulp reveals known markers of TLS, including C-C motif chemokine ligand 19 (CCL19), lysosome-associated membrane glycoprotein 3 (LAMP3), CC chemokine receptor 7 (CCR7), and CD86, present in inflamed dental pulp. Compared with the healthy pulp, types and proportions of immune cells increase, along with enhanced cellular communication. Multiple immunofluorescence staining reveals that typical TLS emerges in dental pulp with pulpitis, consistent with the high expression of CC chemokine ligand 3 (CCL3), which may be a key driver of TLS formation. Moreover, TLS is also observed in a mouse model of pulpitis. These findings collectively offer insights into the formation and function of TLS in response to infection., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Vital pulp therapy (VPT) has recently been reported as an effective approach for preventing and treating carious pulp injury in permanent teeth. Compared with root canal treatment (RCT), which involves complete removal of the pulp tissue, VPT effectively maintains pulp vitality and retains the physiological functions of the pulp. In the research pool, large-scale randomized controlled trials evaluating the treatment outcome of VPT using calcium silicate cements and RCT in cariously exposed permanent teeth are lacking. Here, we present a monocentric clinical protocol to compare the effects of VPT using iRoot BP Plus (Innovative Bioceramix, Vancouver, BC, Canada) as a pulp-capping material with RCT., Methods: The proposed trial is an open-label, single-centre, randomized, controlled, noninferiority trial. In total, 462 patients will be included in this trial according to the following criteria: adult patients (18-50 years old), pulp exposure during the treatment of deep caries in mature permanent teeth, a diagnosis of reversible or partially irreversible pulpitis without apical translucency on X-ray, without periodontitis or systemic disease. Patients with signed informed consent forms will be enrolled and randomly divided into two groups (VPT and RCT) with a balanced treatment allocation (1:1). Clinical evaluations will be conducted at baseline and at 3, 6, 12, and 24 months after treatment, with the potential for extension. The primary outcome measure will be the duration of success. The secondary outcomes will include the success rate at the 1-year follow-up and any adverse reactions. The Kaplan‒Meier method and log-rank test will be used to compare the duration of success of both treatments. For other outcomes, the χ 2 test or Fisher's exact test will be used for categorical variables, and the t test or Mann‒Whitney U test will be used for continuous variables to assess the differences between groups., Discussion: The results of this trial will provide a clinical reference for selecting treatments for carious pulp injuries in permanent teeth., Trial Registration: ClinicalTrials.gov ChiCTR2100051369. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ). Registered on 21 September 2021., (© 2024. The Author(s).)

Background/objectives: This numerical analysis of stress distribution in the dental pulp and neuro-vascular bundle (NVB) of lower premolars assessed the ischemic and degenerative-resorptive risks generated by 2 and 4 N during orthodontic movements (rotation, translation, tipping, intrusion and extrusion) in intact periodontium., Methods: The numerical analysis was performed on nine intact periodontium 3D models of the second lower premolar of nine patients totaling 90 simulations., Results: In intact periodontium, both forces displayed a similar stress distribution for all five orthodontic movements but different amounts of stress (a doubling for 4 N when compared with 2 N), with the highest values displayed in NVB. In intact periodontium, 2 N and 4 N induced stresses lower than the maximum hydrostatic pressure (MHP) with no ischemic risks for healthy intact teeth. The rotation was seen as the most stressful movement, closely followed by intrusion and extrusion. Translation was quantitatively seen as the least stressful when compared with other movements., Conclusions: Larger orthodontic forces of 2 N and 4 N are safe (with any expected ischemic or resorptive risks) for the dental pulp and NVB of healthy intact teeth and in intact periodontium. Nevertheless, rotation and translation movements can induce localized circulatory disturbances in coronal pulp (i.e., vestibular and proximal sides) generating ischemic and resorptive risks on previously treated teeth (i.e., direct and indirect dental pulp capping). The intrusion and extrusion movements, due to the higher NVB-induced deformation when compared with the other three movements, could trigger circulatory disturbances followed by ischemia on previously traumatized teeth (i.e., occlusal trauma).

In the present study, nano-hydroxyapatite (n-HA) powder was extracted from carp bone waste to fabricate porous n-HA substrates by a molding and sintering process. Subsequently, the substrates were loaded with different amounts of sodium fluoride (NaF) through immersion in NaF suspensions for 10, 7.5, and 5 min. The NaF-loaded n-HA substrates were then examined for their structural and physical properties, chemical bonds, loading and release profile, pH changes, cytotoxicity, and osteogenic effect on dental pulp stem cells (DPSCs) at the level of RNA and protein expression. The results showed that the n-HA substrates were porous (> 40% porosity) and had rough surfaces. The NaF could be successfully loaded on the substrates, which was 6.43, 4.50, and 1.47 mg, respectively for n-HA substrates with immersion times of 10, 7.5, and 5 min in the NaF suspensions. It was observed that the NaF release rate was rather fast during the first 24 h in all groups (39.06%, 36.43%, and 39.57% for 10, 7.5, and 5 min, respectively), and decreased dramatically after that, indicating a slow detachment of NaF. Furthermore, the pH of the medium related to all materials was changed during the first 4 days of immersion (from 7.38 to pH of about 7.85, 7.84, 7.63, and 7.66 for C0, C5, C7.5, and C10, respectively). The pH of media associated with the C7.5, and C10 increased up to 4 days and remained relatively constant until day 14 (pH = 7.6). The results of the cytotoxicity assay rejected any toxicity of the fabricated NaF-loaded n-HA substrates on DPSCs, and the cells could adhere to their surfaces with enlarged morphology. The results showed no effect on the osteogenic differentiation at the protein level. Nevertheless, this effect was observed at the gene level., (© 2024. The Author(s).)

Background: An ideal aesthetic restorative material should be attached to the tooth tissues by adhesion, have a smooth surface as possible, should not cause toxic reactions in the pulp and discoloration and microleakage. This study aims at comparatively assess the cytotoxicity of current adhesive systems on human dental pulp cells., Materials and Methods: The adequate density of human pulp cells was observed from the ready cell line. The passaging was performed and the 3rd passage cells were selected. Adhesive systems and MTA were used on the cultures. Trypan blue staining was conducted on the cells at the 1st, 2nd, 3rd days and a count of live and dead cells using a light microscope. The dead cells whose membrane integrity was impaired by staining with trypan blue and the viability rate was determined using live and dead cell numbers. Data analysis was performed using IBM SPSS Statistics 22., Results: A significant difference in vialibity rates between adhesive systems was observed on the first day. No significant statistical differences were observed on the 2nd and 3rd days (p < 0.05)., Conclusion: Futurabond M showed similar biocompatibility with MTA on human pulp cells and it can be applied in cavities with 1-1.5 mm hard tissue between pulp and dentine., (© 2024. The Author(s).)

Purpose The posterior superior alveolar (PSA) block injection is one of many techniques used to provide profound anesthesia for invasive dental procedures. This technique has a high success rate but is not without complication risks. The purpose of this study was to determine if pulpal anesthesia of the maxillary second molar could be achieved using a reduced needle depth of 10mm or 5mm compared to the traditional needle depth of 16mm. Methods Sixty participants were asked to participate in three sessions. Each session started with a pre neural response test, followed by one randomized needle depth PSA injection, and ending with a post neural response test. The neural response test consisted of two parts, a cold refrigerant and a dental probe, on the buccal and interproximal surface of the maxillary second molar. After receiving a positive neural response, each participant received a posterior superior alveolar block injection using a short (21mm), 27-gauge dental needle with a randomized needle penetration depth of 16mm, 10mm, or 5mm. A post neural response test consisting of the same two parts as the pre-test was conducted on the maxillary second molar to evaluate for profound anesthesia. Results Positive neural responses were obtained from 100% of the participants (n=167) during the pre-tests. Study results demonstrated an 85% success rate at the traditional 16mm needle depth and a 93% and 92% success rates for the reduced needle depths of 10mm and 5mm, respectively. Pulpal anesthesia of the maxillary second molar had been achieved at all three needle depths with no statistically significant difference in the rate of success. Furthermore, there were no adverse events observed. Conclusion The reduced needle depth technique showed promise in achieving desired results of pulpal anesthesia with a reduced risk for complications associated with the PSA block injection. Additional studies are recommended to achieve evidence-based support for this reduced needle depth technique., (Copyright © 2024 The American Dental Hygienists’ Association.)

Parkinson's disease (PD) is a neurodegenerative condition characterized by the progressive and selective loss of dopaminergic (DAergic) neurons in the midbrain. The replacement of neuromelanin (NM)-containing DAergic neurons in the substantia nigra and the enhancement of NM concentration could offer a promising and safe approach to treating PD symptoms. The objective of this study was to investigate and compare the potential of human periapical-cysts mesenchymal stem cells (hPCy-MSCs) and dental pulp stem cells (DPSCs) to differentiate into DAergic NM-producing neurons and to generate functional 3-dimensional (3D) midbrain-like organoids in vitro. We assessed the changes in morphology and behavior of neuron-like cells (NLCs) as well as the expression of molecular markers characterizing the DAergic neurons. Furthermore, we observed electrically active and functionally mature DAergic neurons by means of electrophysiological assays, NM dosage assays, and the quantification of dopamine release by high-performance liquid chromatography. Our results demonstrate for the first time that both hPCy-MSCs and DPSCs are capable of differentiating into NLCs, further confirmed by the increase in lactate levels in the medium of cells exposed to neurogenic conditions. Importantly, we have induced such NLCs to further differentiate into functional DAergic NM-producing neurons. Finally, 3D midbrain-like organoids have been produced from oral stem cells: they appear as neurosphere-like structures diffusely expressing the neural marker β-III tubulin and containing NM-like granules. Our findings open up a novel and fascinating opportunity to rethink oral stem cells, and the derived 3D disease models, as a strategic and reliable tool for unveiling the neurodegenerative alterations., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The nature versus nurture debate has intrigued scientific circles for decades. Although extensive research has established a clear relationship between genetics and disease development, recent evidence has highlighted the insufficiency of attributing adverse health outcomes to genetic factors alone. In fact, it has been suggested that environmental influences, such as socioeconomic position (SEP), may play a much larger role in the development of disease than previously thought, with extensive research suggesting that low SEP is associated with adverse health conditions. In relation to oral health, a higher prevalence of caries (tooth decay) exists among those of low SEP. Although little is known about the biological mechanisms underlying this relationship, epigenetic modifications resulting from environmental influences have been suggested to play an important role. This review explores the intersection of health inequalities and epigenetics, the role of early-life social adversity and its long-term epigenetic impacts, and how those living within the lower hierarchies of the socioeconomic pyramid are indeed at higher risk of developing diseases, particularly in relation to oral health. A deeper understanding of these mechanisms could lead to the development of targeted interventions for individuals of low SEP to improve oral health or identify those who are at higher risk of developing oral disease., (© 2024. The Author(s).)

Although physical exercise is extremely important for health and a good lifestyle, it can trigger oxidative stress, inflammation, and muscle fatigue. The aim of this study was to determine changes in dental tissues and the mandible created by creatines monohydrate (CrM) supplementation together with low and high-intensity exercise (HIE). The study material comprised Balb/c male mices, which were separated into two groups for the application of low and HIE on a running band. CrM supplement was administered together with the exercise. At the end of the experiment period, dental tissue samples were surgically removed and examined histopathologically and immunohistochemically (TNF-α and lL-1β).As a result of the histopathological examinations, in the pulp, oedema, vascular congestion, and capillary dilatation were seen to be statistically significantly increased in the Group 3 mices that performed HIE compared to the control group (p = 0.001, p = 0.003, p = 0.001, respectively). A statistically significant increase was observed in periodontal ligament (PDL) degeneration, and disruption of the continuity and separation of collagen fibers in Group 3 compared to the control group (p = 0.001). In the immunohistochemical examination, TNF-α and IL-1β positivity was observed in Group 3, and this was significantly increased compared to the control group (p = 0.001, p = 0.000).Exposure of the mices to low and HIE caused histological and immunohistochemical changes in dental pulp and PDL, and it was determined that the use of CrM could have a protective effect against these changes. RESEARCH HIGHLIGHTS: The results of this study showed negative effects of HIE in the dental pulp and PDL, which play an important role in dental health. CrM was seen to be effective in preventing these negative effects., (© 2024 The Author(s). Microscopy Research and Technique published by Wiley Periodicals LLC.)

Background: Orthodontic tooth movement (OTM) is a biological process that can influence the function of the pulp, including its innervation. The excitability of the nerve fibres of the pulp may be altered by forces exerted on the nerve fibres or by reduced blood flow to the pulp. The aim of this clinical study was to evaluate the sensitivity of the dental pulp during levelling and during the phase of space closure, to assess the role of certain controlled risk factors., Methods: Twenty-two adolescent participants requiring orthodontic space closure in transcanine sector were enrolled in a prospective clinical study. Patients were observed before OTM, after levelling and 1 month during active space closure. The sensitivity threshold of the pulp was measured using the electric pulp test (EPT). Dental models were obtained using an intraoral scanner, allowing measurement of interdental distances and calculation of OTM speed. The teeth were categorized according to position and tooth type., Results: The EPT values increased significantly during orthodontic treatment (one-way RM-ANOVA, P = .014). There was a significant difference in EPT values between the tooth categories. Teeth with a single root adjacent to the residual space had the highest EPT thresholds (two-way RM-ANOVA, P < .001; Holm-Sidak, P < .05)., Conclusions: OTM reduced pulpal sensitivity. Pulpal sensitivity during active space closure was similar to sensitivity during the levelling phase. The pulpal sensitivity of molars was less affected by OTM than that of single-rooted teeth, while teeth closer to the gap had a significantly higher pulpal sensitivity threshold during active OTM., (© 2024 The Authors. Orthodontics & Craniofacial Research published by John Wiley & Sons Ltd.)

Objective: To investigate the outcomes and factors influencing the success of vital pulp treatment (VPT) in permanent teeth with carious pulp exposure and signs and symptoms of irreversible pulpitis (IP)., Materials and Methods: Dental records from 2016 to 2023 of patients who received VPT for carious pulp-exposed permanent teeth with IP symptoms were reviewed. Outcomes were assessed using clinical and radiographic criteria. Univariate and multivariate analyses were performed to identify factors affecting treatment success. The Kaplan-Meier estimator was used to compare survival probabilities., Results: The overall success and survival rates were 88.24% and 97.06%, respectively. Success rates for direct pulp capping, partial pulpotomy, and full pulpotomy were 87.7%, 92.0%, and 87.7%, respectively. Key factors influencing outcomes included the presence of periapical radiographic lesions, type of pulp dressing material, and quality of the final restoration. Full pulpotomy demonstrated the highest survival time, followed by partial pulpotomy and direct pulp capping., Conclusion: VPT in permanent teeth with carious pulp exposure and IP symptoms shows high success rates. Crucial factors include periapical radiographic findings, type of pulp dressing material, and quality of the final restoration. Full pulpotomy exhibited the longest survival time., Clinical Relevance: VPT in teeth with IP symptoms shows promising outcomes, highlighting the importance of certain clinical factors in treatment success., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study investigated the bioactive effects of retinoic acid and ascorbic acid on hSCAPs in vitro., Design: Cells were obtained from human third molars (n=4) and characterized for mesenchymal stem cell markers by flow cytometry. The experimental groups: control (α-MEM); vehicle control group (α-MEM + 0.17 % DMSO); retinoic acid 0.1, 1, and 10 µM; and ascorbic acid 3, 30, and 300 µM (n=8) were tested for cell viability (alamarBlue; 1, 3, and 7 days), total collagen synthesis (Sirius Red; 1 and 7 days), mineralized matrix formation (Alizarin red; 14 days), and the regulation of gene expression related to mineralization (ALPL and DSPP), cell migration (ITGAV and CXCL12) angiogenesis (VEGFA) and collagen synthesis (COL1A1 and COL3A1; RT-qPCR) on 1 and 7 days. ACTB and GAPDH were used as reference genes. Data were analyzed by ANOVA and complementary tests at a 5 % significance level., Results: Ascorbic acid 300 µM increased viability, and retinoic acid reduced it dose-dependently. Retinoic acid 0.1 µM and ascorbic acid 30 and 300 µM increased mineralized matrix formation and total collagen synthesis, and retinoic acid 10 µM decreased. On day 1, 0.1 µM retinoic acid upregulated the gene expression of COL1A1, COL3A1, VEGFA, CXCL12, ALPL, DSPP e ITGAV, and 300 µM ascorbic acid upregulated COL1A1, COL3A1 and DSPP. However, on day 7, retinoic acid downregulated ALPL, COL3A1, CXCL12, and VEGFA and downregulated ITGAV and VEGFA., Conclusion: Retinoic acid 0.1 µM and ascorbic acid 300 µM biostimulated hSCAPs to differentiate into pro-regenerative phenotypes with potential application for REPs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This clinical study assessed photobiomodulation (PBM) induced analgesic effects of diode lasers and an LED light source on the dental pulp. Baseline responses to electric pulp testing (EPT) were recorded in 93 healthy unrestored premolar teeth in 26 adults (age range 22-63 years) attending a private dental practice. The teeth were irradiated on buccal and lingual aspects of the crown, by placing the tips on the middle third of the crown of the teeth, on separate days for each of 4 different light sources (660, 808, or 904 nm diode lasers, or a novel multi-wavelength LED light source (700-1100 nm)) using comparable parameters (100 mW, 30 s, 6 J). EPT scores were measured after a further 1-, 2-, 5- and 20-min. Discomfort caused by PBM therapy was recorded using the Wong-Baker scale. EPT changes were tracked over time using repeated measures analysis of variance. Baseline EPT scores were very consistent between different days (linear regression r 2 0.9422-0.9648). All PBM devices caused a significant elevation in EPT at 5 min, with an earlier onset at 2 mins for 904 nm and LED. The LED was the only light source that elevated scores at 20 min. Across 2-20 min, when ranked by effectiveness, the greatest EPT elevations were seen for LED, followed by 904 nm, then 660 nm and finally 808 nm. Discomfort during PBM was most common with 904 nm, followed by 808 nm. No discomfort occurred from the LED. Among the light sources utilized, the LED multi-wavelength system demonstrated the largest increase in EPT readings, suggesting its potential as a non-pharmacological alternative for achieving dental analgesia compared to diode lasers., (© 2024. The Author(s).)

The objective of the study was to assess the indirect cytotoxicity of 600 ppm and 1500 ppm nano silver fluoride (NSF) compared to other commercial cariostatic agents. 56 dentin discs with 0.4 mm in thickness were obtained from intact human molars and adapted to artificial pulp chambers (APCs). The discs were divided into seven groups according to treatment (n = 8): no treatment (positive control-PC), 29% hydrogen peroxide (negative control-NC), 30% Cariestop (CS30), 38% Riva Star (RS38), 38% Advantage Arrest (AA38), 600 ppm NSF (NSF600), and 1500 ppm NSF (NSF1500). The cariostatic agents were applied on the occlusal surface of the dentin discs (facing upward), and the pulp surface (facing downward) remained in contact with the culture medium. Immediately after the treatments, the extracts (DMEM + cariostatic agent components diffused through the discs) were collected and applied to MDPC-23 cells, which were assessed for viability (CV-alamarBlue, live/dead), adhesion/spreading (F-actin), alkaline phosphatase (ALP) activity, and mineralization nodule (MN) formation. The data were statistically analyzed by ANOVA/Games-Howell (p = 0.05). CV and ALP activity in CS30, RS38, AA38, and NSF600 were similar to PC (p > 0.05). MN formation significantly decreased only in NC, CS30, RS38, and AA38 compared to PC (p < 0.001). Only NSF600 and NSF1500 did not differ from PC (p > 0.05) with mineralization nodules, and this specific cell activity significantly decreased in all other groups (p < 0.05). NSF solutions (600 ppm and 1500 ppm) did not cause transdentinal toxicity on MDPC-23 cells., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Introduction: This study explores a relatively unexplored aspect of multiple sclerosis (MS) by examining the sensitivity threshold of dental pulp as a potential indicator of neuropathy in MS patients. Building upon earlier research that focused on assessing the response to electrical pulp testing in MS patients who did not have a history of trigeminal neuralgia, this survey is aimed at delving into the relationship between MS duration and the threshold for stimulation in response to pulp sensitivity tests. Materials and Methods: This study encompassed a total of 124 maxillary central incisors from patients diagnosed with relapsing-remitting multiple sclerosis (RRMS). The participants were uniform in terms of age, falling within the 18-50 years range, and all had RRMS with no history of trigeminal neuralgia. The electric pulp sensitivity test was conducted on all samples, and the results of the electric pulp testing (EPT) were recorded according to the grade of the pulp tester that elicited a response. The threshold was considered reached when the patient first experienced a burning sensation after EPT application and the use of 1,1,1,2-tetrafluoroethane spray. Data analysis employed paired t -tests, Fisher's exact test, and Spearman correlation, with a significance level set at p < 0.05. Results: Based on the study's findings, the average response value to EPT was 2.69 ± 1.17, while the response time to the cold test was 2.61 ± 1.03 s. There was no statistically significant difference in the response to the cold test based on age ( p = 0.45). However, it was observed that the mean response time to the cold test was significantly longer among male participants ( p = 0.001). No significant differences were identified in the pulpal response to EPT or the cold test between patients with and without sensory-motor involvement ( p > 0.05). Furthermore, Spearman's analysis revealed a noteworthy positive correlation between the electrical pulp threshold and the time taken to respond to the cold test ( p = 0.025, r = 0.2). Conclusions: The utilization of the pulpal sensitivity test in MS patients holds promise for practical clinical use. Notably, individuals with a more extended duration of the disease exhibited a notably elevated threshold for both the EPT and the cold test conducted on their maxillary central incisors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Fatemeh Owlia et al.)

Background and Aims: Delayed implementation of new knowledge into clinical practice poses patient safety risks. This study investigates agreement on use of the dental caries interventions, sealing, and stepwise excavation., Methods: A cross-sectional questionnaire survey, based on 11 constructed cases with descriptions of patient symptoms, radiographic, and clinical findings. Interrater agreement on dental caries- and pulp diagnoses and interventions were measured with Cohen's and Light's κ . The data collection period was September 28 to November 5, 2021. To explore variations in use and knowledge factors, we examined Danish dentists' attitudes toward continuing education., Results: Based on 243 responses, moderate interrater agreement for dental caries and pulp diagnoses and weak agreement on interventions were seen. The agreement with the gold standard for caries was moderate. No agreement was found for dental pulp diagnosis, and for interventions the agreement was weak. No pattern in agreement with the gold standard was seen in relation to case difficulty level. The majority reported knowing of and using stepwise excavation, in conflict with findings that less than half chose stepwise excavation in cases, where considered appropriate. One in four (25%) reported to be unfamiliar with sealing, and half (50%) use sealing regularly. Better access to continuing education and for universities to offer continuing education as alternatives to one-sided private market were requested., Conclusion: Some patients may receive too radical treatment despite available less invasive evidence-based effective treatments. Dentists acknowledge the importance of continuing education. Easier access and perhaps more incentives for seeking out high-quality continuing education from trustworthy sources are needed., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Aim: This study aimed to evaluate the effectiveness of combining Channa striata extract with calcium hydroxide (Ca(OH)2) in reducing lymphocyte counts and interleukin (IL)-1β levels in inflamed pulp teeth., Materials and Methods: A laboratory experimental setup with a posttest control group (CG) design was employed. Thirty-two rat incisor teeth were divided into four groups: a positive CG (100% Ca(OH)2), treatment 1 (25% C. striata extract + 75% Ca(OH)2), treatment 2 (50% C. striata extract + 50% Ca(OH)2), and treatment 3 (75% C. striata extract + 25% Ca(OH)2). These test materials were applied to Class 1 cavities extending to the pulp roof, with samples collected on days 1, 3, 5, and 7. Data were analyzed using analysis of variance and post hoc least significant difference tests., Results: In all the groups, the highest levels of lymphocytes and IL-1β were observed on day 3, followed by a decline on days 5 and 7. The combination of C. striata extract with Ca(OH)2 significantly reduced inflammatory markers, particularly lymphocyte and IL-1β levels., Conclusion: The extract of C. striata holds significant potential as an innovative therapeutic approach for managing inflamed dental pulp., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Conservative Dentistry and Endodontics.)

Purpose: This study aimed to assess the performance of 2-dimensional (2D) imaging with microscopy coils in delineating teeth and periodontal tissues compared with conventional 3-dimensional (3D) imaging on a 3 T magnetic resonance imaging (MRI) unit., Materials and Methods: Twelve healthy participants (4 men and 8 women; mean age: 25.6 years; range: 20-52 years) with no dental symptoms were included. The left mandibular first molars and surrounding periodontal tissues were examined using the following 2 sequences: 2D proton density-weighted (PDw) images and 3D enhanced T1 high-resolution isotropic volume excitation (eTHRIVE) images. Two-dimensional MRI images were taken using a 3 T MRI unit and a 47 mm microscopy coil, while 3D MRI imaging used a 3 T MRI unit and head-neck coil. Oral radiologists assessed dental and periodontal structures using a 4-point Likert scale. Inter- and intra-observer agreement was determined using the weighted kappa coefficient. The Wilcoxon signed-rank test was used to compare 2D-PDw and 3D-eTHRIVE images., Results: Qualitative analysis showed significantly better visualization scores for 2D-PDw imaging than for 3D-eTHRIVE imaging (Wilcoxon signed-rank test). 2D-PDw images provided improved visibility of the tooth, root dental pulp, periodontal ligament, lamina dura, coronal dental pulp, gingiva, and nutrient tract. Inter-observer reliability ranged from moderate agreement to almost perfect agreement, and intra-observer agreement was in a similar range., Conclusion: Two-dimensional-PDw images acquired using a 3 T MRI unit and microscopy coil effectively visualized nearly all aspects of teeth and periodontal tissues., Competing Interests: Conflicts of Interest: None, (Copyright © 2024 by Korean Academy of Oral and Maxillofacial Radiology.)

The dental pulp is a highly innervated tissue transmitting pain-related sensations in the tooth. Consequently, understanding the intricacies of its innervation mechanism in odontogenesis is crucial for gaining insights into dental pain and developing dental pain-modulating agents. This study examined neuroregulatory molecules such as neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin-4 [NTF-4], and neurturin [NRTN]) and neuroinhibitory factors (slit2, ephrin isoforms and netrin-1) in developing rat teeth with follicles. NGF, BDNF and NRTN transcriptions showed time-dependent upregulation, particularly during the root formation stage. In contrast, NTF-4 mRNA was highly expressed at the cap stage, but became downregulated over time. Slit2 and ephrin-B2 expression was distinct at the cap stage and then downregulated in a time-dependent manner. Ephrin-A5 and netrin-1 expression did not significantly change. Immunofluorescence analysis revealed a robust expression of both ephrin-B2 and slit2 in the outer and inner dental epithelia of the enamel organ, a non-neurogenic tissue, during the cap stage of 3rd molar germs. In contrast, BDNF was predominantly localized in dental papilla cells and odontoblasts during the root formation stage. These results suggest that neuroregulatory molecules, such as BDNF, slit2 and ephrin-B2, may be important in identifying therapeutic targets for modulating dental pulp pain., (© 2024 The Author(s). Anatomia, Histologia, Embryologia published by Wiley‐VCH GmbH.)

Collagen X is an extracellular matrix protein, usually found in the hypertrophic cartilage destined to be mineralized. It is intimately associated with the mineralization process of the mammalian hard tissues, and particularly, regulating the compartmentalization of matrix components. Despite the fact that the dentine of the tooth is highly mineralized, there are no previous reports to indicate the presence of collagen X in this connective tissue. Here we report, for the first time, its presence in mammalian dentine based on micromorphological and immunohistochemical data. We hypothesize that the collagen X in dentine may in the long term arrest the progression of the mineralization front towards the soft tissue components of the pulp that are not destined to be mineralized., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Hypoxia is relevant to several physiological and pathological processes and this also applies for the tooth. The adaptive response to lowering oxygen concentration is mediated by hypoxia-inducible factors (HIFs). Since HIFs were shown to participate in the promotion of angiogenesis, stem cell survival, odontoblast differentiation and dentin formation, they may play a beneficial role in the tooth reparative processes. Although some data were generated in vitro, little is known about the in vivo context of HIFs in tooth development. In order to contribute to this field, the mouse mandibular first molar was used as a model.The expression and in situ localisation of HIFs were examined at postnatal (P) days P0, P7, P14, using RT-PCR and immunostaining. The expression pattern of a broad spectrum of hypoxia-related genes was monitored by customised PCR Arrays. Metabolic aspects were evaluated by determination of the lactate level and mRNA expression of the mitochondrial marker Nd1.The results show constant high mRNA expression of Hif1a, increasing expression of Hif2a, and very low expression of Hif3a during early postnatal molar development. In the examined period the localisation of HIFs in the nuclei of odontoblasts and the subodontoblastic layer identified their presence during odontoblastic differentiation. Additionally, the lower lactate level and higher expression of mitochondrial Nd1 in advanced development points to decreasing glycolysis during differentiation. Postnatal nuclear localisation of HIFs indicates a hypoxic state in specific areas of dental pulp as oxygen demands depend on physiological events such as crown and root dentin mineralization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Pulpitis is associated with tooth hypersensitivity and results in pulpal damage. Thermosensitive transient receptor potential (TRP) ion channels expressed in the dental pulp may be key transducers of inflammation and nociception. We aimed at investigating the expression and role of thermo-TRPs in primary human dental pulp cells (hDPCs) in normal and inflammatory conditions., Experimental Approach: Inflammatory conditions were induced in hDPC cultures by applying polyinosinic:polycytidylic acid (poly(I:C)). Gene expression and pro-inflammatory cytokine release were measured by RT-qPCR and ELISA. Functions of TRPA1 channels were investigated by monitoring changes in intracellular Ca 2+ concentration. Mitochondrial superoxide production was measured using a fluorescent substrate. Cellular viability was assessed by measuring the activity of mitochondrial dehydrogenases and cytoplasmic esterases. TRPA1 activity was modified by agonists, antagonists, and gene silencing., Key Results: Transcripts of TRPV1, TRPV2, TRPV4, TRPC5, and TRPA1 were highly expressed in control hDPCs, whereas TRPV3, TRPM2, and TRPM3 expressions were much lower, and TRPM8 was not detected. Poly(I:C) markedly up-regulated TRPA1 but not other thermo-TRPs. TRPA1 agonist-induced Ca 2+ signals were highly potentiated in inflammatory conditions. Poly(I:C)-treated cells displayed increased Ca 2+ responses to H 2 O 2 , which was abolished by TRPA1 antagonists. Inflammatory conditions induced oxidative stress, stimulated mitochondrial superoxide production, resulted in mitochondrial damage, and decreased cellular viability of hDPCs. This inflammatory cellular damage was partly prevented by the co-application of TRPA1 antagonist or TRPA1 silencing., Conclusion and Implications: Pharmacological blockade of TRPA1 channels may be a promising therapeutic approach to alleviate pulpitis and inflammation-associated pulpal damage., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases., Competing Interests: Declaration of Competing Interest The authors declare that there is no competing interests., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives: During caries progression, dental pulp is increasingly pathologically affected. Since the accurate assessment of pulp is of vital importance in clinical decision-making, this study aimed to evaluate pulpal condition in the early stages of caries via laser Doppler (LD) flowmetry and histologic analysis and determine their agreement., Methods: Fourteen patients with severe dental crowding were included. Prior to extractions and orthodontic treatment, dental pulp condition of 52 premolars was evaluated via LD flowmetry. Teeth were assessed for the presence of caries and lesions were graded according to the International Caries Detection and Assessment System (ICDAS). After extractions, teeth were split and histologically stained for endothelial cells with anti-von Willebrand factor and Movat pentachrome for collagen. Volume densities of vessels (V vasc ) and collagen were calculated., Results: There was a significant negative correlation between LD flow and V vasc of the dental pulp with ICDAS grade. Pulpal LD flow and V vasc in teeth with the initial lesion were increased, decreasing with progressing stages of caries. A significant positive correlation between the the pulpal LD flow and V vasc , and a negative correlation of LD flow with collagen fibre density were noted., Conclusions: Caries affects the physiology of the dental pulp, initially with increasing vascularity, and decreasing vascularity at later stges of caries progression. Collagen contents increase with grades of ICDAS. LD flow shows good agreement with the histologic constitution of the dental pulp. Use of clinical measurements of pulpal LD flow could provide a good noninvasive indication of pulpal vascular state and its health., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Estimating the post-mortem interval (PMI) of human remains based on the histomorphology of dental pulp parameters is promising, but available evidence is scarce and sometimes contradictory without a scientific model. The aim of the study is to characterise the histomorphological changes of dental pulp associated with the decomposition of human remains by a qualitative and quantitative approach. The main aim is to establish a correlation based on post-mortem (PM) dental pulp histomorphology and the PMI, and whether pulp degradation could be an available medico-legal tool for PMI estimation beyond the first week after death (late PMI). The eligible sample consisted of 27 sound teeth from 16 healthy patients aged 16 to 72 years due to orthodontic or oral surgery treatment, to create PMI's simulating the death of the subject as the time elapsed from tooth avulsion. Data collected from patients (sex, date of birth, tooth position, date and hour of the avulsion, date and hour of pulp extraction) were anonymised in accordance with the requirements of Faculty of Dental Medicine of the University of Lisbon. The sample was divided into 9 groups of 3 teeth according to different PMI sets from T0 (baseline) up to 2 weeks (T0, 7, 12, 24, 36, 48, and 72 hours, 1 and 2 weeks). All the dental samples were stored at room temperature up to the time of pulp extraction and then prepared with haematoxylin and eosin stain. High-resolution microscopy was performed to obtain histological images. An operator performed the qualitative evaluation of blood vessels, collagen fibres, and the extra-cellular matrix (ECM) in PM pulps and measured the variation in cells/nuclei density by counting 6 different ROIs (Regions of Interest) for each pulp manually and automatically (quantitative analysis). Qualitative results showed that the degeneration of dental pulp appears 7 hours after death but histological changes in vessels, fibres, and ECM in PM dental pulp are characterised by high variability, consequently it is not possible to generalise the results for early PMIs. Quantitative measurements proved that cell count cannot be standardised due to the presence of superimposed layers of cells and nuclei fragmentation. Odontoblasts did not demonstrate evidence of cellular or nuclear lysis up to 14 PM suggesting their applicability in late PMIs. Future research will focus on late PMIs and different techniques of tooth preparation., Competing Interests: The authors report no conflicts of interest in this work., (Copyright© 2024 IOFOS This work is published and licensed by International Organization for Forensic Odonto-Stomatology.)

Objective: Calcium silicate cements (CSCs) are often used in endodontics despite some limitations related to their physical properties and antibacterial efficacy. This study aimed to develop and demonstrate the viability of a series of CSCs that were produced by sol-gel method and further modified with mesoporous bioactive glass nanoparticles (MBGNs) and collagen, for endodontic therapy., Methods: Calcium silicate (CS) particles and MBGNs were synthesized by the sol-gel method, and their elemental, molecular, and physical microstructure was characterized. Three CSCs were developed by mixing the CS with distilled water (CS+H 2 O), 10 mg/mL collagen solution (CS+colH 2 O), and MBGNs (10 %) (CSmbgn+colH 2 O). The mixing (MT) and setting (ST) times of the CSCs were determined, while the setting reaction was monitored in real-time. Antibacterial efficacy against Enterococcus faecalis (E. faecalis) and regenerative potential on dental pulp stem cells (DPSCs) were also analyzed., Results: The CS+H 2 O displayed a ST comparable to commercial products, while CSmbgn+colH 2 O achieved the longest MT of 68 s and the shortest ST of 8 min. All the experimental CSCs inhibited the growth of E. faecalis. Additionally, compared to the control group, CSCs supported cell proliferation and spreading and mineralized matrix production, regardless of their composition., Significance: Tested CSCs presented potential as candidates for pulp therapy procedures. Future research should investigate the pulp regeneration mechanisms alongside rigorous antibacterial evaluations, preferably with multi-organism biofilms, executed over extended periods., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Histological techniques are essential for the microscopic study and investigation of the human dental pulp. The aim of this study was to evaluate the impact of decalcification-free technique by examining dental pulp morphology by histological staining with haematoxylin and eosin and immunohistochemistry., Materials and Methods: The sample consisted of 30 healthy third molars extracted for orthodontic indication, the pulp tissue was obtained by removing the mineralized tissues, separating the enamel and dentine and by marking with a flexible diamond disc on the coronal surface and longitudinal axis of the root. These guides made it possible to separate the fragments and obtain the pulp tissue for fixation and staining with H&E and subsequent immunohistochemistry with CD34 and S-100 antibodies., Results: The technique showed preservation of pulp morphology with adequate preservation of microscopic structures. No alterations in tissue viability were observed. The staining allowed an accurate assessment of vascular and nervous components by means of CD34 and S-100 markers, respectively., Conclusions: This technique allows preservation of pulp tissue, maintaining viable tissue for histological analysis and immunohistochemistry tests, as well as reducing sample processing time.

(1) Background: The aim of this study was to compare the cytotoxicity of selected resin-modified materials used in direct contact with the dental pulp (TheraCal LC, TheraCal PT, and ApaCal ART) with calcium silicate cement (Biodentine). (2) Methods: The mouse fibroblast Balb/3T3 cell line and the extracts of tested materials in four concentrations were used for the testing. An MTT assay was performed in three independent experiments with six replicates for each concentration of tested material. The cell viability (%) and cytotoxicity were expressed (cytotoxic effect is considered in cases where the cell viability is lower than 70%). The mean of the cell viability and the standard deviation were expressed for each material at all concentrations. ANOVA and Dunnet's post hoc tests were used for the statistical analysis. All of these tests were performed at the 0.05 significance level. (3) Results: At all concentrations, the cell viability was statistically significantly lower ( p ≤ 0.002) for all tested materials compared to Biodentine. ApaCal ART showed a high level of cytotoxicity at all concentrations (cell viability lower than 47.71%, p < 0.0001). The same result was found for TheraCal LC at concentrations of 100%, 50% and 25% and TheraCal PT at concentrations of 100% and 50%. TheraCal LC at a 10% concentration (cell viability 68.18%) and TheraCal PT at a 25% concentration (cell viability 60.63%) indicated potential cytotoxicity. TheraCal PT at a 10% concentration was not found to be cytotoxic (cell viability 79.18%, p = 0.095). (4) Conclusion: The resin-modified calcium silicate and calcium phosphate materials showed higher cytotoxic potential, so they should be used with caution when in direct contact with the dental pulp.

Objectives: The aim of this research was to assess the diffusion dynamics of silver and fluoride ions after 38% silver diamine fluoride (SDF) solution application on dentine of varying thicknesses over 24 weeks., Methods: Bovine dentine discs of 5.5 mm in diameter were prepared and separated into 3 groups with thicknesses of 0.5 mm (group 1), 1.0 mm (group 2), and 1.5 mm (group 3). The diameter and number of dentinal tubules of discs were assessed. Each disc received a topical application of 0.05 mL 38% SDF solution. The deionised water in the tube was collected weekly for 24 weeks. The silver and the fluoride ion concentrations in the collected deionised water were determined. Generalised estimating equations was used to explore the potential effects of the key factors on the silver/fluoride diffusion., Results: The amount of silver and fluoride ion diffusion through dentine almost levelled off after 4 weeks and showed a decline trend over 24 weeks. The mean (SD) 24-week cumulative ion diffusion through dentine in groups 1, 2, and 3 was as follows: 20 (4) μg, 10 (2) μg, and 5 (1) μg for silver (P < .05) and 18 (2) μg, 13 (2) μg, and 7 (1) μg for fluoride (P < .05), respectively., Conclusions: Silver and fluoride ion diffusion through dentine showed a decline trend over 24 weeks. The diameter and the number of dentinal tubules on dentine with different thicknesses affects the ion diffusion dynamics. This study provides indications on the pattern of silver/fluoride ions diffusion through dentine to pulp after 38% SDF application. An increased amount of silver/fluoride diffuses through dentine into the pulp with decreased remaining dentine thickness., Competing Interests: Conflict of interest The authors state that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine-phosphate-guanine (CpG) motifs (CpG-ODNs) are ligand molecules for Toll-like receptor 9 (TLR9), which is expressed by odontoblasts in vitro and dental pulp cells. This study determined the effects of CpG-ODNs on pulpal immunomodulatory response and repair following injury. Briefly, the upper right first molars of three-week-old mice were extracted, immersed in Type A (D35) or B (K3) CpG-ODN solutions (0.1 or 0.8 mM) for 30 min, and then replanted. Pulpal healing and immunomodulatory activity were assessed by hematoxylin-eosin and AZAN staining, as well as immunohistochemistry. One week following the operation, inflammatory reactions occurred in all of the experimental groups; however, re-revascularization and newly formed hard tissue deposition were observed in the pulp chamber of all groups at week 2. A positive trend in the expression of immune cell markers was observed toward the CpG-ODN groups at 0.1 mM. Our data suggest that synthetic CpG-ODN solutions at low concentrations may evoke a long-lasting macrophage-TLR9-mediated pro-inflammatory, rather than anti-inflammatory, response in the dental pulp to modulate the repair process and hard tissue formation. Further studies are needed to determine the effects of current immunomodulatory agents in vitro and in vivo and develop treatment strategies for dental tissue regeneration.

Dental pulp stem cells (DPSCs) originate from the neural crest and the present mesenchymal phenotype showed self-renewal capabilities and can differentiate into at least three lineages. DPSCs are easily isolated with minimal harm, no notable ethical constraints, and without general anesthesia to the donor individuals. Furthermore, cryopreservation of DPSCs provides this opportunity for autologous transplantation in future studies without fundamental changes in stemness, viability, proliferation, and differentiating features. Current approaches for pulp tissue regeneration include pulp revascularization, cell-homing-based regenerative endodontic treatment (RET), cell-transplantation-based regenerative endodontic treatment, and allogeneic transplantation. In recent years, a novel technology, organoid, provides a mimic physiological condition and tissue construct that can be applied for tissue engineering, genetic manipulation, disease modeling, single-cell high throughput analysis, living biobank, cryopreserving and maintaining cells, and therapeutic approaches based on personalized medicine. The organoids can be a reliable preclinical prediction model for evaluating cell behavior, monitoring drug response or resistance, and comparing healthy and pathological conditions for therapeutic and prognostic approaches. In the current review, we focused on the promising application of 3D organoid technology based on DPSCs in oral and maxillofacial tissue regeneration. We discussed encountering challenges and limitations, and found promising solutions to overcome obstacles., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The European Society of Endodontology published in 2023, the S3-level clinical practice guidelines, which supersede the Quality Guidelines for Endodontic Treatment published in 2006., Objectives: This review aims to summarize and compare the above guidelines to support their dissemination., Method: A narrative synthesis of the main differences alongside tabulation according to the main themes., Results: Three tables were prepared according to the following themes: diagnosis of pulpal and apical condition; treatment of pulpitis; and treatment of nonvital pulp and apical periodontitis., Conclusions: A compared and simplified message regarding the most recent clinical practice guidelines has been prepared., Registration: Not applicable as a narrative review., (© 2024 The Authors. International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)

Teeth are vulnerable to structural compromise, primarily attributed to carious lesions, in which microorganisms originating from the oral cavity deteriorate the mineralized structures of enamel and dentin, subsequently infiltrating the underlying soft connective tissue, known as the dental pulp. Nonetheless, dental pulp possesses the necessary capabilities to detect and defend against bacteria and their by-products, using a variety of intricate defense mechanisms. The pulp houses specialized cells known as odontoblasts, which encounter harmful substances produced by oral bacteria. These cells identify pathogens at an early stage and commence the immune system response. As bacteria approach the pulp, various cell types within the pulp, such as different immune cells, stem cells, fibroblasts, as well as neuronal and vascular networks, contribute a range of defense mechanisms. Therefore, the immune system is present in the healthy pulp to restrain the initial spread of pathogens, and then in the inflamed pulp, it prepares the conditions for necrosis or regeneration, so inflammatory response mechanisms play a critical role in maintaining tissue homeostasis. This review aims to consolidate the existing literature on the immune system in dental pulp, encompassing current knowledge on this topic that explains the diverse mechanisms of recognition and defense against pathogens exhibited by dental pulp cells, elucidates the mechanisms of innate and adaptive immunity in inflamed pulp, and highlights the difference between inflamed and normal pulp tissue.

Objective: To investigate the incidence of accessory canals and the variation in root canal morphology of permanent mandibular incisors and canines in Pakistani population using Cone Beam Computed Tomography (CBCT)., Methods: A cross-sectional study was conducted in University College of Dentistry, The University of Lahore, Pakistan after getting institutional ethical permission from January 2020 to September 2022. The data included records of 111 patients consisting of 444 permanent mandibular incisors and 222 permanent mandibular canines. Accessory root, root canals and Vertucci canal configuration for each tooth was recorded. Data analysis was done using SPSS v20. Descriptive statistics were calculated for each anatomical parameter. Chi-square test was applied to determine association of gender with the presence of accessory roots and root canals., Results: Among the 111 records evaluated, 48.6% were males and 51.4% were females. No accessory root was found in the central and lateral incisors. However, an accessory root was found in 4.9% of the canines. The incidence of accessory canals in the central incisors, lateral incisors and canines was 18.9%, 25.2% and 10.4% respectively. The most common canal configuration in teeth with accessory canals was Type-III, followed by Type-II and Type-V., Conclusion: None of the central or lateral incisor showed accessory root while it was detected in 4.9% canines. The frequency of accessory root canal was found to be 18.9%, 25.2% and 10.4% in central incisors, lateral incisors and canines respectively. The most common canal configuration was Type-I, followed by Type-III and Type-II. Type-V, VI and VII were less common., Competing Interests: Conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Aims: Dental pulp stem cells (DPSCs) contain a population of stem cells with a broad range of differentiation potentials, as well as more lineage-committed progenitors. Such heterogeneity is a significant obstacle to experimental and clinical applications. The aim of this study is to isolate and characterize a homogenous neuronal progenitor cell population from human DPSCs., Methodology: Polysialylated-neural cell adhesion molecule (PSA-NCAM+) neural progenitors were isolated from the dental pulp of three independent donors using magnetic-activated cell sorting (MACS) technology. Immunofluorescent staining with a panel of neural and non-neural markers was used to characterize the magnetically isolated PSA-NCAM+ fraction. PSA-NCAM+ cells were then cultured in Neurobasal A supplemented with neurotrophic factors: dibutyryl cyclic-AMP, neurotrophin-3, B27 and N2 supplements to induce neuronal differentiation. Both PSA-NCAM+ and differentiated PSA-NCAM+ cells were used in Ca 2+ imaging studies to assess the functionality of P2X3 receptors as well as membrane depolarization., Results: PSA-NCAM+ neural progenitors were isolated from a heterogeneous population of hDPSCs using magnetic-activated cell sorting and anti-PSA-NCAM MicroBeads. Flow cytometry analysis demonstrated that immunomagnetic sorting significantly increased the purity of PSA-NCAM+ cells. Immunofluorescent staining revealed expression of pan-neuronal and mature neuronal markers, PGP9.5 and MAP2, respectively, as well as weak expression of the mature sensory markers, peripherin and islet1. ATP-induced response was mediated predominately by P2X3 receptors in both undifferentiated and differentiated cells, with a greater magnitude observed in the latter. In addition, membrane depolarizations were also detected in cells before and after differentiation when loaded with fast-voltage-responding fluorescent molecule, FluoVolt™ in response to potassium chloride. Interestingly, only differentiated PSA-NCAM+ cells were capable of spontaneous membrane oscillations., Conclusions: In summary, DPSCs contain a population of neuronal progenitors with enhanced neural differentiation and functional neural-like properties that can be effectively isolated with magnetic-activated cell sorting (MACS)., (© 2024 The Authors. International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)

Background: Understanding the root canal morphology is essential for the success of root canal treatment. Therefore, this study aimed to evaluate and analyze the root canal configuration of maxillary premolars using Cone Beam Computed Tomography in the Pakistani subpopulation., Method: This cross-sectional study utilized CBCT scans from two distinct centres: Aga Khan University in Karachi and Jinnah MRI and Body Scans in Lahore. The CBCT images were visualized using GALAXIS version 1.9 (SICAT GmbH and Co. KG, Bonn, Germany), integrated within the Sirona Dental System (D-64625 Bensheim, Germany). The scanning parameters were standardized at 85 kV, 7 mA, with a 15-s exposure time and a voxel size of 0.16 mm. A total of 707 CBCT scans were collected, encompassing 2180 maxillary premolars. Root canal configurations were classified based on (Ahmed et al. Int Endod J. 2017;50(8):761-70). Statistical analyses were performed using SPSS version 26, employing the Chi-square test with a significance level set at p < 0.05., Results: The distribution of root canal morphologies varied significantly with age and gender. Among maxillary premolars, 50% exhibited the typical configuration of 2 MPMB 1 L 1 (two roots, single canal in each buccal and lingual root), while 26% of maxillary right second premolars displayed 1 MPM 1 (one root, one canal). Overall, 1 MPM 1 accounted for 27.4% of the total cases in the second premolars. There was no statistically significant relationship between age and root canal distribution in either first premolars (p = 0.338) or second premolars (p = 0.833). Regarding gender, a significant difference was observed in the distribution of right maxillary 1st premolars (p = 0.022*), with a higher prevalence among females., Conclusion: This study offers significant insights into the anatomical variations of root canals in maxillary premolars across diverse regional subpopulations in Pakistan. While specific root canal configurations were prevalent, the findings indicate no statistically significant correlation between age and root canal morphology in maxillary premolars. However, a notable gender disparity was observed in the distribution of the right maxillary first premolars., (© 2024. The Author(s).)

Objective: To evaluate histologically and radiographically the potential of dog's immature roots with apical periodontitis to regenerate after regenerative endodontic treatment using mesoporous silica nanoparticles (MSNs) with/without bone morphogenic protein (BMP-2) as scaffolds., Methods: In 4 mongrel dogs, 56 immature teeth with 96 roots were infected, resulting in necrotic pulps and periapical pathosis. According to the evaluation time (Group I = 30 days and Group II = 90 days), 90 roots were divided into two equal groups (45 roots each) and 6 roots used to replace any lost root during the procedure. The two main groups were further divided according to treatment protocol into 5 subgroups (9 roots each): blood clot (BC subgroup), mesoporous silica nanoparticles scaffold only (MSNs subgroup), mesoporous silica nanoparticles impregnated with BMP2 (MSNs + BMP2 subgroup), infected teeth without treatment (+ ve control subgroup) and normal untouched teeth (-ve control subgroup). All teeth surfaces were coated with Tincture iodine and calcium hydroxide was applied prior to treatment protocols. Then, teeth were restored with glass ionomer filling to seal the remaining part of the access cavity. Radiography evaluation of the increase in root length, root thickness and occurrence of apical closure were performed. Following the sacrifice of the two dogs at each time of evaluation, histopathological analysis was performed and included the inflammatory cells count, bone resorption, tissue ingrowth, deposition of hard tissue, and closure of the apical part. All data were statistically analyzed., Results: Compared to BC subgroup, MSNs and MSNs + BMP-2 subgroups exhibited significant higher increase in root length and thickness as well as higher vital tissue in-growth and new hard tissue formation in group II (P < 0.05). MSNs + BMP-2 subgroup had significant higher increase in root length and thickness as well as significant lower inflammatory cell count than MSNs subgroup in both groups (P < 0.05). There were no significant differences between MSNs and MSNs + BMP-2 subgroups regarding new hard tissue formation in both groups and apical closure in group I (P > 0.05)., Conclusion: MSNs with/without BMP-2 scaffolds enabled the continuing growth of roots in immature teeth with necrotic pulps and periapical pathosis. Addition of BMP-2 to MSNs scaffold improved its outcome in regenerative endodontics., Clinical Relevance: MSNs with/without BMP-2 scaffolds may alternate blood clot for regenerative endodontic treatment of immature teeth with necrotic pulps., (© 2024. The Author(s).)

Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Han et al.)

Objectives: This study aimed to investigate the endodontic characteristics of mandibular premolars with dens evaginatus (DE) that require endodontic treatment., Materials and Methods: Patients who underwent endodontic treatment were enrolled. The inclusion criteria were patients who underwent root canal treatment in the lower permanent teeth with DE and were followed up for at least 1 year. Preoperative clinical and radiographic variables were obtained. The frequency distribution of the preoperative variables was compared using the χ 2 or Fisher's exact tests. The significance of the change in periapical health index (PAI) and root development stages before and after treatment was examined using the Wilcoxon signed-rank test., Results: A total of 150 teeth of 134 patients with an average age of 15.3 years were included. The percentage distribution comparison of the preoperative variables and obturation techniques revealed significant differences in pulpal and periapical diagnosis, and percussion, and especially regarding age, root development stage, and PAI. Age was the only statistically significant preoperative variable associated with root growth ( p < 0.05)., Conclusions: Approximately, 60% of DEs requiring endodontic treatment had immature roots. Age being the most significant predisposing factor, early treatment provides the greatest opportunity for full root development., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. The Korean Academy of Conservative Dentistry.)

Introduction: Root dentin formation is an important process in tooth development. We tried to identify potential genes that regulate root dentin formation which could be potentially used for the regeneration and repair of defective or damaged dental roots. Methods: Tissues harvested from the labial and lingual sides of mouse incisors were used for microarray analysis. Gene ontology (GO) analysis of differentially expressed genes indicated the critical role of extracellular matrix in the discrepancy of dentin formation between root and crown, for which hemicentin-1 ( Hmcn1 ) was selected as the target gene. Single-cell RNA sequencing analysis the expression pattern of Hmcn1 at different developmental stages in mouse molars. The spatiotemporal expression of HMCN1 in mouse incisors and molars was detected by immunohistochemical staining. The functions of HMCN1 in human dental pulp cells, including proliferation, differentiation and migration, were examined in vitro by CCK8 assay, BrdU assay, wound-healing assay, ALP staining and alizarin red staining, respectively. Results: It was showed that HMCN1 expression was more pronounced in papilla-pulp on the root than crown side in mouse incisors and molars. In vitro experiments presented inhibited dentinogenesis and migration after HMCN1 -knockdown in human dental pulp cells, while there was no significant difference in proliferation between the HMCN1 -knockdown group and control group. Discussion: These results indicated that HMCN1 plays an important role in dentinogenesis and migration of pulp cells, contributing to root dentin formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cui, Li, Wang, Li, Xie, Zhou, Zhang and Sun.)

Introduction: Vital pulp therapy (VPT) is performed to preserve dental pulp. However, the biocompatibility of the existing materials is of concern. Therefore, novel materials that can induce pulp healing without adverse effects need to be developed. Resolvin D2 (RvD2), one of specialized pro-resolving mediators, can resolve inflammation and promote the healing of periapical lesions. Therefore, RvD2 may be suitable for use in VPT. In the present study, we evaluated the efficacy of RvD2 against VPT using in vivo and in vitro models., Methods: First molars of eight-week-old male Sprague-Dawley rats were used for pulpotomy. They were then divided into three treatment groups: RvD2, phosphate-buffered saline, and calcium hydroxide groups. Treatment results were assessed using radiological, histological, and immunohistochemical (GPR18, TNF-α, Ki67, VEGF, TGF-β, CD44, CD90, and TRPA1) analyses. Dental pulp-derived cells were treated with RvD2 in vitro and analyzed using cell-proliferation and cell-migration assays, real-time PCR ( Gpr18 , Tnf-α , Il-1β , Tgf-β , Vegf , Nanog , and Trpa1 ), ELISA (VEGF and TGF-β), immunocytochemistry (TRPA1), and flow cytometry (dental pulp stem cells: DPSCs)., Results: The formation of calcified tissue in the pulp was observed in the RvD2 and calcium hydroxide groups. RvD2 inhibited inflammation in dental pulp cells. RvD2 promoted cell proliferation and migration and the expression of TGF-β and VEGF in vitro and in vivo . RvD2 increased the number of DPSCs. In addition, RvD2 suppressed TRPA1 expression as a pain receptor., Conclusion: RvD2 induced the formation of reparative dentin, anti-inflammatory effects, and decreased pain, along with the proliferation of DPSCs via the expression of VEGF and TGF-β, on the pulp surface in pulpotomy models., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zulema Arias reports financial support was provided by 10.13039/501100001691Japan Society for the Promotion of Science. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Hyaluronic acid (HA), known for diverse properties, was investigated for its potential in dental pulp therapy. This study investigated the potential of HA in dental pulp therapy by examining the physical properties and effects of zinc oxide eugenol (ZOE) pulpotomy materials containing varying HA concentrations on rat molar teeth. In vitro tests assessed compressive strength and hardness of ZOE materials blended with HA (0.5%, 1%, 3%) and HA gels (0.54%, 0.8%). 120 samples, encompassing the control group, underwent compressive strength testing, while 60 samples were designated for hardness assessment. In vivo experiments on rat molars studied histological effects of HA-containing ZOE on dental pulp over 1 week and 1 month. Gels with HA concentrations of 0.5%, 1%, and 0.54% were used in pulpotomy on 22 rats. Each rat underwent the procedure on four teeth, with one tooth serving as a control, totaling 88 teeth subjected to the intervention. In the analyses, SPSS 22.0 was used and the significance level was set at P = 0.05. Findings showed that HA at 0.5% maintained compressive strength, but higher concentrations decreased mechanical properties significantly (P = 0.001). Histological assessments indicated better outcomes with lower HA concentrations in terms of odontoblast layer continuity (P = 0.005 at 1 month) and pulp vitality (P = 0.001 at 1 week and P = 0.018 at 1 month). The study suggests HA holds promise for pulpotomy and regenerative endodontic treatments, but further research is needed to understand long-term clinical implications., (© 2024. The Author(s).)

Objective: To systematically evaluate the clinical performance of deep margin elevation (DME) technique in terms of pulpal and periodontal health of teeth., Methods and Materials: An exploratory search was performed in PubMed, Scopus, Embase, Web of Science, and Google Scholar up to September 2023 by two authors independently. This systematic review was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Systematic Reviews (PRISMA-SR) and registered with PROSPERO-CRD42022382082. A custom-designed spreadsheet was used to extract the data. The quality of each study was evaluated by means of the Joanna Briggs Institute (JBI) risk of bias (ROB) tool specific for each study design., Results: A total of 5363 articles was obtained through an electronic database search, the grey literature, and a hand search. 2814 duplicates were removed, and an additional 2535 articles were also removed, as they did not meet the eligibility criteria. Following the screening of titles and abstracts, 16 articles were selected for full text reading, from which 10 articles were included for final qualitative analysis. DME was predominantly done with resin-based composite or glass ionomer cement (GIC). Parameters like periodontal pocket depth and bleeding on probing were within normal limits in all teeth with DME. Only one study checked the histological outcome and concluded that DME had no negative effect on the periodontium. Most of the studies used indirect restoration (composite/lithium disilicate/Emax) over the DME layer. The follow-up period ranged between 6 months and 12 years., Conclusion: The level of evidence of this review is low, but DME was successful in all teeth, without any deleterious effect on pulp and periodontium., (©Operative Dentistry, 2024.)

Objectives: The inner mechanism of how diabetes affects dental pulp of patients with periodontitis has seldom been reported. We collected clinical samples and explored the influence of diabetes and periodontitis on the pathological change of dental pulp., Methods: Dental pulp from healthy individuals and patients with periodontitis with or without diabetes were collected based on strict inclusion and exclusion criteria. Dental pulp was morphologically observed; advanced glycation end products (AGEs) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX1) were examined. Oxidative stress (OS), inflammatory indices, and apoptotic levels were assessed., Results: Morphologically, fibrous structure in the dental pulp of patients with diabetic periodontitis (DP) group was sparse and disordered, and the blood vessel wall was thickened. Diabetes related indexes as AGEs and LOX1 were upregulated. Superoxide dismutase 2 expression was decreased, and OS level was increased. Matrix metalloproteinase 3 and other relevant proinflammatory cytokines levels were increased. The elevated OS and inflammation contributed to upregulation of apoptotic levels in DP group., Conclusions: Diabetes aggravates the pathological changes in the dental pulp of periodontitis patients possibly due to upregulated AGEs and LOX1. Our results highlight the importance of early oral intervention in patients with DP., (© 2023 Wiley Periodicals LLC.)

Background: Antibiotic pastes used as intracanal medication in cases of revascularization therapy might cause negative effects on tooth properties, such as a reduction in dentin microhardness. This in vitro study investigated dentin microhardness in three different locations distancing from the canal lumen after 20 days of treatment with a tri-antibiotic paste (ciprofloxacin, metronidazole, and minocycline), and with a double-antibiotic paste (ciprofloxacin and metronidazole), with calcium hydroxide [Ca(OH) 2 ] Ultracal TM XS-treated dentin as comparison. Material and Methods: Human mandibular premolars (n = 48) had the root canals cleaned and shaped and were used to produce dentin slices. Dentin slices remained immersed in the medications for 20 days. The Knoop microhardness (KHN) test was performed before (baseline/Day-0) and after treatment (Day-20) with the medications. Indentations were made at 25 µm, 50 µm, and 100 µm distances from the root canal lumen. The KHN was compared intra-group using Wilcoxon's test. Independent groups were compared using Mann-Whitney's and Kruskal-Wallis' tests, at α = 5%. Results: The microhardness in all the tested groups was reduced at Day-20 in comparison with Day-0 ( p < 0.001) (intra-group comparison/same distances). The Day-0 values were similar, and the Day-20 values were higher for the Ca(OH) 2 group ( p < 0.05) (comparison between groups/same distances). Conclusions: Calcium hydroxide for 20 days would be preferred rather than antibiotic pastes to minimize the expected reduction in dentin microhardness during regenerative procedures.

Regenerative endodontic procedures (REP) aim at reestablishing tooth vitality by replacing the irreversibly damaged dental pulp removed by the dental practitioner with a new functional one. The current treatment of advanced caries relies on the replacement of the inflamed or necrosed dental pulp with an inert filling material. This leads to a functional but non-vital tooth, which lacks the ability to sense dental tissue damage, and to protect from further bacterial attack. Therapeutic strategies inspired by tissue engineering called REP propose to regenerate a fully functional dental pulp directly in the canal space. Promising results were obtained using dental pulp mesenchymal stem cells (DP-MSCs) in combination with bio-inspired artificial and temporary 3D hydrogels made of extracellular matrix molecules such as collagen and fibrin biomacromolecules. However, the uncontrolled mechanisms of DP regeneration from DP-MSCs in 3D biomacromolecules fail to regenerate a fully functional DP and can induce fibrotic scarring or mineralized tissue formation to a non-negligible extent. The lack of knowledge regarding the early molecular mechanisms initiated by DP-MSCs seeded in ECM-made hydrogels is a scientific lock for REP. In this study, we investigated the early DP-MSC-response in a 3D fibrin hydrogel. DP-MSCs isolated from human third molars were cultured for 24 h in the fibrin hydrogel. The differential transcript levels of extracellular and cell surface genes were screened with 84-gene PCR array. Out of the 84 genes screened, 9 were found to be overexpressed, including those coding for the integrin alpha 2 subunit, the collagenase MMP1 and stromelysins MMP3, MMP10 and MMP12. Over-expression of ITGA2 was confirmed by RT-qPCR. The expression of alpha 2 integrin subunit protein was assessed over time by immunoblot and immunofluorescence staining. The increase in the transcript level of MMP1, MMP3, MM10 and MMP12 was confirmed by RT-qPCR. The overexpression of MMP1 and 3 at the protein level was assessed by immunoblot. MMP3 expression by DP-MSCs was observed by immunofluorescence staining. This work demonstrates overexpression of ITGA2 and of MMP1, 3, 10 and 12 by DP-MSCs cultured in a fibrin hydrogel. The main preliminary extracellular and cell surface response of the DP-MSCs to fibrin hydrogel seems to rely on a ITGA2/MMP3 axis. Further investigations are needed to precisely decipher the role of this axis in dental pulp tissue building. Nevertheless, this work identifies extracellular and cell surface molecules that could be potential checkpoints to be targeted to guide proper dental pulp tissue regeneration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Aim: The European Society of Endodontology outlines best practices for the management of deep caries and the pulp. Despite evidence supporting vital pulp treatments (VPTs) as predictable alternatives to conventional endodontic treatment, studies have shown they are not widely adopted in the UK. This study aimed to explore the barriers to implementation of VPTs by primary care general dental practitioners (GDPs)., Methodology: Qualitative one-to-one semi-structured online interviews were conducted with purposively sampled UK GDPs. Interview transcripts were analysed using reflexive thematic analysis. Recurring themes were iteratively refined as additional transcripts were reviewed., Results: Eleven participants were interviewed. A range of barriers to the provision of VPTs were identified, which aligned with two core themes: 'Motivational barriers to service provision' and 'Educational access & opportunities'. Sub-themes included lack of access to materials and equipment, deficiencies in knowledge of treatment (including protocols, outcomes and prognosis), lack of confidence (in treatment efficacy and clinical ability), time constraints and public dental service funding and remuneration., Conclusions: This study identifies barriers to the widespread adoption of VPTs among primary care GDPs in public and private settings. Economic constraints, practitioner confidence, time limitations and educational gaps are key challenges. Addressing these may require systemic changes such as policy interventions, education and improved resource allocation., (© 2024 The Author(s). International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)