AIM:Endodontic infections can spread, leading to life-threatening systemic infections. However, the available literature is limited concerning factors associated with a higher risk. This study aimed to characterize patients hospitalized with a severe endodontic infection spread and explore the course of endodontic infection and treatment prior to hospitalization. METHODOLOGY:This retrospective cohort study included patients hospitalized with a severe odontogenic infection (SOI) of endodontic origin at the Department of Oral & Maxillofacial Surgery, Copenhagen University Hospital, between the 1st of November 2012 and the 31st of December 2019. Hospital records (demographic, anamnestic, and radiographic data) and dental records (preoperative, intraoperative, and radiographic data) were analyzed with descriptive statistics, chi-square test of homogeneity, Fisher's exact test, independent sample t-test, Welch's ANOVA, and, if indicated, post hoc test (level of statistical significance: p < 0.05). RESULTS:Out of 384 patient cases hospitalized with SOI, 229 (59.6%) were considered to have endodontic aetiology. Among these, apical periodontitis (AP) was related to root-filled (RF) teeth in 44 cases (19.2%), teeth with ongoing endodontic treatment in 44 cases (19.2%), endodontically untreated teeth in 121 cases (52.8%), and unknown endodontic treatment status in 20 cases (8.7%). Men were more often hospitalized with endodontically untreated teeth (56.2%) compared to RF teeth (34.1%) (p = 0.023). Patients hospitalized with endodontically untreated teeth had a higher mean age (46.5 [±20.1] years), more diseases (48.7%), and consumed more medications (53.7%) compared to those with ongoing endodontic treatment (38.9 [±13.5] years, 19.5% and 27.3%, respectively) (p = 0.025, p = 0.005, and p = 0.011, respectively). In total, 85% of the root fillings were assessed as insufficient regarding length and seal. From dental records, it was documented that 34% received systemic antibiotics (ABs) for their AP without initiating operative endodontic treatment. CONCLUSIONS:Endodontic infections, especially from endodontically untreated teeth, were the most frequent cause of SOIs leading to hospitalization. The quality of root fillings was generally insufficient, and numerous patients were prescribed systemic ABs prior to hospitalization without concomitant operative endodontic treatment. This indicates the importance of well-performed operative dental treatments to decrease the risk of severe infection spread.
AIM:Pulpitis is a common and painful disease characterised by complex and dynamic immune responses and may lead to irreversible tissue damage or tooth loss. Macrophages act as key sentinels that exhibit differential metabolic reprogramming, tightly orchestrating the immune microenvironment. However, the specific metabolic mechanisms governing macrophage-driven inflammatory activation in pulpitis remain unclear. Here, we reveal a specific lipid metabolism-driven immune pathway within macrophages in pulpitis. METHODOLOGY:An integrative analysis of single-cell RNA sequencing (scRNA-seq), lipidomics and bulk RNA sequencing (RNA-seq) was employed to characterise macrophage subpopulations and metabolic alterations in pulpitis. Western blot and immunofluorescence staining were performed to validate the expression of phospholipase A2 group VII (PLA2G7) in human pulp tissues. In vitro, an inflammatory THP-1 macrophage model was established to investigate the effects of PLA2G7 inhibition and lysophosphatidylcholine (LPC) supplementation, and macrophage inflammatory activation was assessed by RT-qPCR, Western blot, ELISA and immunofluorescence staining. Bioinformatic analyses and fluorescence recovery after photobleaching (FRAP) experiments were conducted to identify the upstream transcriptional regulator of PLA2G7 and explore its regulatory mechanism. A murine pulpitis model treated with the PLA2G7 inhibitor darapladib was used to evaluate the anti-inflammatory effects by ELISA, immunohistochemical and immunofluorescence staining. RESULTS:ScRNA-seq, lipidomics and RNA-seq analyses identified a distinct lipid-associated macrophage subset with high PLA2G7 expression in pulpitis. The abundance of this subset increased with inflammatory severity. Immunofluorescence and Western blot validated increased PLA2G7 expression in lipid-associated macrophages in pulpitis tissues. In vitro, inhibition of PLA2G7 significantly suppressed inflammatory responses, whereas supplementation with LPC attenuated this anti-inflammatory effect. In vivo, darapladib-mediated inhibition of PLA2G7 significantly attenuated pulpitis progression and reduced macrophage activation in mice. Mechanistically, integrative bioinformatic analysis identified JunD proto-oncogene (JUND) as a transcriptional regulator of PLA2G7, potentially via liquid-liquid phase separation (LLPS)-mediated transcriptional condensates. CONCLUSIONS:These findings identify PLA2G7 as a potential biomarker for pulpitis and reveal a JUND-PLA2G7-LPC signalling axis linking lipid metabolism to macrophage-mediated inflammatory responses, providing a novel perspective for preserving dental pulp vitality.
AIM:Pulp-dentine complex repair following injury is fundamental to preserving tooth vitality and function. Despite advances in understanding reparative dentinogenesis, the molecular mechanisms orchestrating odontogenic differentiation of human dental pulp stem cells (hDPSCs) remain fragmented, lacking systematic integration across transcriptomic, proteomic and metabolomic levels. This study employs integrated multi-omics approaches to identify key regulatory pathways during odontogenic differentiation and elucidate the underlying mechanisms controlling pulp-dentine complex repair. METHODOLOGY:Single-cell RNA sequencing was performed on human carious and healthy pulp tissues. Temporal proteomic and metabolomic profiling was conducted during hDPSCs' odontogenic differentiation. Based on multi-omics integration revealing glutathione metabolism as a central regulatory node, hDPSCs were treated with L-buthionine-sulfoximine (BSO) or exogenous glutathione (GSH). Intracellular reactive oxygen species (ROS), GSH levels, mitochondrial membrane potential and mitophagy markers (PINK1/Parkin) were quantified. siRNA-mediated PINK1 knockdown was performed to assess the involvement of PINK1 in GSH-regulated odontogenic differentiation. A mouse molar injury model evaluated GSH effects on tertiary dentine formation in vivo. RESULTS:Single-cell transcriptomic analysis revealed enrichment of oxidative stress response pathways in mesenchymal stem cells from injured pulp. Multi-omics integration identified glutathione metabolism as a central regulatory pathway, with glutamate-cysteine ligase catalytic subunit (GCLC) progressively upregulated during differentiation. BSO treatment depleted intracellular GSH, elevated ROS levels, suppressed PINK1/Parkin-mediated mitophagy and impaired odontogenic differentiation. GSH supplementation restored mitophagy activity and rescued differentiation capacity in vitro. PINK1 depletion impaired odontogenic differentiation and markedly attenuated the pro-differentiation effects of exogenous GSH. In vivo, GSH administration enhanced tertiary dentine formation and activated mitophagy pathways in injured dental pulp. CONCLUSIONS:Our findings establish that the GCLC-mediated GSH antioxidant system orchestrates the odontogenic differentiation of dental pulp cells and pulp-dentine complex repair via the PINK1/Parkin-mitophagy axis, revealing a novel metabolic-oxideative signalling circuit as a potential therapeutic target for regenerative endodontics.
BACKGROUND:Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are critical intracellular pattern recognition receptors that orchestrate innate and adaptive immune responses. Their dysregulated activation is mechanistically linked to the pathogenesis of numerous inflammatory diseases. In endodontics, pulpitis and apical periodontitis represent highly prevalent inflammatory conditions, primarily caused by bacterial invasion, which significantly impact patients' quality of life. Current studies demonstrate that NLR-mediated immunity plays a significant role in driving pulpal inflammation and periapical bone resorption. OBJECTIVES:This review aims to systematically synthesize current knowledge on the expression, regulatory mechanisms and functional roles of NLRs in dental pulp and periapical tissues. Furthermore, it seeks to critically evaluate the therapeutic potential of targeting NLR pathways for the management of endodontic diseases. METHOD:This narrative review employed a systematic search strategy. A comprehensive literature search was conducted across MEDLINE/PubMed and Scopus databases from inception to January 2026. Search terms combined concepts related to NLRs (covering all subfamilies and members, e.g., 'NOD-like receptors', 'NLRP3', 'NLRP6', 'NLRP12', 'NOD1', 'NOD2') and endodontics ('pulpitis', 'apical periodontitis', 'endodontic disease'). Relevant original research articles in English were included for narrative synthesis. RESULTS:The review delineates the structural characteristics and signalling pathways of NLRs, citing 48 articles. It details their specific expression patterns and functional roles within the specialized microenvironments of the dental pulp and periapical tissues. The analysis also surveys a promising landscape of NLR-targeted therapeutic strategies, including small-molecule inhibitors, biologics, nanotechnology-based delivery systems and genetic engineering. CONCLUSION:NLRs are pivotal regulators of the host immune response in endodontic diseases. A deeper understanding of their expression and mechanisms offers novel insights into disease pathogenesis. Modulating NLR pathways presents a promising, though challenging, therapeutic frontier for developing more effective treatments for pulpitis and apical periodontitis.
BACKGROUND:Root canal treatment (RCT) is recommended for compromised teeth in patients with radiation therapy (RT) for head and neck cancer (HNC), to minimise extraction-related osteoradionecrosis (ORN). However, literature on endodontic outcomes in irradiated patients is scarce. This retrospective clinical study aimed to investigate healing outcome, survival, and their associated prognostic factors in teeth that received non-surgical RCT in irradiated HNC patients. METHODS:Patients who underwent RT for HNC and subsequently received RCT between 2011 and 2022 were identified from electronic clinical records. Healing outcome and tooth survival were assessed from clinical and radiographic data. Radiation dose to each tooth and its periapical region was quantified by delineating these structures on RT planning CT scans. Healing was classified as healed/healing or diseased using predefined clinical and radiographic criteria. Associations between prognostic factors and healing or survival were analysed using mixed-effects logistic and Cox regression models, respectively. RESULTS:A total of 170 teeth in 82 patients were included. Among teeth reviewed at 1-4 years, 82.4% (108/131) were classified as healed/healing. Estimated survival was 85.8% (95% CI: 78.1%-94.3%) at 7 years, declining to 55.7% (95% CI: 37.4%-55.7%) at a maximum follow-up of 132 months. Pre-operative mobility significantly predicted both poorer healing (OR = 10.0; 95% CI: 1.47-68.5) and increased extraction risk (HR = 44.5; 95% CI: 6.38-310). Increasing age at RCT initiation was also associated with tooth loss (HR = 1.09 per year; 95% CI: 1.01-1.17). Radiation dose to the tooth or periapical region was not associated with healing or survival, and no cases of ORN were observed. CONCLUSIONS:Healing and survival of endodontically treated teeth in irradiated HNC patients were favourable. Pre-operative tooth mobility was associated with poorer healing and increased risk of tooth loss and should be considered during pre-radiotherapy dental assessment. In contrast, no statistically significant association was detected between radiation dose to the tooth or periapical region and healing or survival outcomes in this cohort. These findings support endodontic treatment as a means of preserving compromised teeth in irradiated jaws and reducing the risk of extraction-related ORN.
AIM:To characterize the translational pathway of endodontic technology from patent filing to clinical availability, with four objectives: (i) determine the grant rate and jurisdictional distribution; (ii) characterize temporal dynamics of the grant process; (iii) map distribution across technology categories; and (iv) evaluate maturity and regulatory status in a strategic subset. METHODOLOGY:A retrospective cohort of 201 patent families was identified from European Patent Office Espacenet (Cooperative Patent Classification class A61C5*), priority years 2012-2014. Variables included technology category, jurisdiction, granted status in the USA, Europe, and Japan, time until first grant, and patent status at 31 December 2025. A strategic subset (n = 20), defined as families with identifiable regulatory or commercial signals, was further analysed using a Technology Maturity Index (TMI, 1-5) and regulatory signals (Food and Drug Administration (FDA) clearance, Conformité Européenne (CE) marking, clinical evidence). Kaplan-Meier analysis modelled time to first grant, and translational attrition was mapped across the translation process. RESULTS:Of 201 endodontic patent families, 112 (55.7%) were granted in at least one major market. Median time until the first patent was granted was 1652 days (Interquartile Range (IQR) 1290-2043). Instrumentation dominated (80.1%), and energy-based devices showed a numerically higher grant rate (66.7%), although this difference was not statistically significant. Twenty families (10.0%) carried identifiable regulatory or commercial signals; 16 (80.0%) reached near-commercial maturity (TMI ≥ 4) and 15 achieved TMI = 5, representing 7.5% of the original cohort. CONCLUSIONS:Endodontic technology translation is prolonged and highly selective, showing progressive narrowing from filing to commercial realization, with only 7.5% (15/201) of the families reaching confirmed full market availability. These findings provide a descriptive framework for interpreting emerging technologies and highlight the need to consider both time and attrition when evaluating innovation in endodontics.
BACKGROUND:Obtaining an accurate preoperative diagnosis ascertaining the level of pulpal inflammation is fundamental to selecting subsequent endodontic care. Conventional diagnostic methods, including thermal and electric pulp testing, percussion and radiographic assessment, rely largely on subjective patient responses and indirect indicators of pulpal health, resulting only in limited discrimination between pulp necrosis and vitality. These limitations often hinder reliable differentiation between levels of pulpitis such as reversible and irreversible pulpitis, which may result in either under-treatment or over-treatment. Advances in the understanding of pulpal pathophysiology and the success of vital pulp treatment techniques have highlighted the need for objective, accurate, biologically relevant, molecular-based point-of-care diagnostic approaches. OBJECTIVES:This narrative review aimed to synthesise current evidence on the biological basis of pulpal inflammation, critically evaluate the limitations of conventional diagnostic methods, while exploring the potential role of molecular biomarkers and preoperatively/intraoperatively sourced biological fluids in the objective assessment of pulpitis. METHODS:A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus and Web of Science databases. Relevant peer-reviewed original research articles, narrative and systematic reviews and experimental and clinical studies related to pulpitis, caries-induced pulpal inflammation, diagnostic methods, biomarkers and biological fluids were included. The selected literature was qualitatively synthesised to identify prevailing themes. RESULTS:The findings indicate that pulpitis is characterised by complex immune and vascular responses that are inadequately captured by traditional diagnostic tests. Biomarkers associated with inflammatory activity, tissue breakdown and immune regulation potentially offer objective measures of disease presence, severity and progression. Among preoperative biological fluids, gingival crevicular fluid (GCF) demonstrates superior site-specificity and biological relevance compared with saliva and systemic blood, despite limitations related to sample volume and standardisation. In addition, intraoperative biological sources such as dentinal fluid and pulpal blood provide direct, site-specific information reflective of the pulpal microenvironment, with potential to enhance diagnostic accuracy during clinical treatments. CONCLUSION:GCF-based molecular diagnostics are biologically plausible tools to assist preoperative diagnosis having shown encouraging preliminary findings for objective pulpal assessment. However, their clinical utility requires validation through prospective biomarker-outcome studies, standardised diagnostic thresholds and strong analytical validation before considering routine endodontic application.
AIM:To prospectively compare treatment outcomes for orthograde canal obturation using Ortho MTA III (OMTA) with the continuous wave of compaction (CWC) using gutta-percha (GP) and AH Plus sealer, and to identify associated predictive factors. METHODOLOGY:Informed consent was obtained (110 patients), and single- or two-rooted permanent teeth (n = 120) diagnosed with pulp necrosis (or previously treated) and asymptomatic apical periodontitis or chronic apical abscess (periapical index, PAI ≥ 3) were randomly assigned to two groups (n = 60/group). The canals were prepared to a minimal apical size #40 (ISO) based on their initial file size, disinfected and obturated by either CWC or OMTA using an enhanced disinfection protocol (GP disinfected, new gloves after each intraoperative radiograph and before starting obturation). Clinical and periapical radiographic examinations were conducted by two calibrated, independent endodontists during follow-up periods of at least 12 months. Success rates and associated predictive factors (tooth-, operator- and patient-related) were analysed statistically using binary and multiple logistic regression (p < 0.05). RESULTS:The median recall period was 30 months (14-48 months), and 104 teeth were finally analysed (recall rate: 86.67%). No significant differences in success rate were observed between the groups (p > 0.05) under both loose (OMTA: 88.24%, CWC: 83.02%) and strict criteria (OMTA: 64.71%, CWC: 58.49%). Multivariate analysis revealed that age (OR = 5.735, 95% CI: 1.286-25.577, p = 0.022), periapical lesion size (OR = 6.596, 95% CI: 1.397-31.138, p = 0.017) and PAI score (OR = 2.081, 95% CI: 1.047-4.136, p = 0.036) were significant predictors of treatment failure. CONCLUSIONS:Orthograde obturation of infected canals with Ortho MTA III demonstrated comparable success and treatment outcomes to those filled with GP and sealer by CWC, supporting its potential as a clinically viable alternative for the obturation of infected root canals. TRIAL REGISTRATION:cris.nih.go.kr registration number: KCT00099939.
AIM:To evaluate the outcome of pulpectomy, root canal treatment (RCT) and orthograde retreatment in permanent teeth performed by undergraduate dental students and to assess the influence of various variables. METHODOLOGY:Electronic dental health records at the Department of Odontology, University of Copenhagen, Denmark were analysed covering pulpectomy, RCT and orthograde retreatment performed by dental students 2012-2022 and follow-ups until 2025. Patient-, tooth- and treatment-related variables and follow-up periods were monitored. Effective treatment outcome was defined as absence of pain, no or reduced periapical radiolucency. Chi-square was used for comparisons and uni- and multi-variable logistic regression analyses to assess outcome-related factors. Odds ratio (OR) estimates were presented with 95% confidence interval (CI). RESULTS:One thousand four hundred and sixty-six teeth in 1304 individuals were included. Median follow-up was 14.5 months (interquartile range: 7.6-31.7 months). The overall proportion of effective treatment outcome was 89% (92% for pulpectomy, 87% for RCT and 81% for orthograde retreatment). Using RCT as the reference, pulpectomy was associated with lower odds of non-effective outcome (OR:0.61/CI:0.42-0.88). In multivariable analysis, non-smoking, younger age, premolar teeth and longer follow-up periods had lower odds of non-effective treatment (p < 0.05). Indirect compared to direct restoration was associated with lower odds of non-effective treatment (OR:0.29/CI:0.18-0.47), p < 0.001. CONCLUSIONS:Non-surgical endodontic treatments performed by undergraduate dental students showed a high rate of effective treatment outcome. Pulpectomy showed better outcome compared with RCT and orthograde retreatment. Smoking, older age, non-premolar teeth, shorter follow-up periods and direct restorations were associated with higher odds of non-effective treatment. Awareness of these factors may help improve the predictability of endodontic treatment in an undergraduate clinical setting. Taking the retrospective design and study limitations into account, the results should be interpreted with caution.
BACKGROUND:Major advances in pulp biology, biomaterials, and tissue engineering have fuelled the development of regenerative strategies aimed at preserving or restoring pulp vitality. Despite this progress, the clinical translation of these discoveries remains limited or absent. AIMS:Although there is a global agenda to reduce and replace animal use in medical research, we believe that a critical missing link in the translational pipeline of regenerative endodontics innovations is the lack of rigorously validated, clinically relevant preclinical models to use in advancing promising in vitro findings through regulatory processes to human application. METHODS:While novel alternative methodologies (NAMs), including microfluidics, organoids, and organ-on-chip systems, offer human-relevant in vitro models and are rapidly transforming early-stage screening and mechanistic studies, they are currently insufficient to replicate the complex systemic elements provided by animal models, which are essential for demonstrating in vivo efficacy of regenerative therapies. Regulatory approval of devices, drugs, and biologics continues to require robust preclinical evidence generated in whole-organism systems, particularly when complex interactions involving immunity, vascularisation, innervation, and aging are central to therapeutic success. RESULTS:In this perspective article, we discuss key scientific, methodological, and logistical considerations for the systematic development and validation of orthotopic animal models in regenerative endodontics research. We place particular emphasis on vital pulp treatment as a biologically and clinically relevant framework for studying pulp repair and in demonstrating the efficacy of novel therapies. We highlight the challenges that have hindered consensus in model selection and standardisation, and emphasise the need for coordinated transdisciplinary efforts to overcome these barriers. CONCLUSION:We argue that prioritising standardised orthotopic vital pulp treatment models, in combination with evolving NAMs, represents a critical step to bridge the gap between mechanistic discoveries and clinical translation in regenerative endodontics.
Root canal therapy (RCT) is the primary treatment modality for pulpal and periapical diseases. Although the fundamental objective of RCT has remained unchanged for over a century, its technical details have been continuously refined and transformed. Preoperative diagnostic approaches have evolved from two-dimensional imaging to three-dimensional volumetric reconstructions and, more recently, to artificial intelligence-assisted analytical frameworks. Treatment modalities have progressed from manual instrumentation to motor-driven systems and guided or robotic-assisted interventions. Disinfection strategies have also begun to shift from passive chemical irrigation towards actively guided nano-enabled systems. Moreover, obturation materials have advanced from inert substances to bioactive compounds and, prospectively, to adaptive trends. These transitions reflect not only technological progress but also the continuing efforts of endodontists to improve precision, safety, efficiency, and biological outcomes. However, the primary goal of RCT remains the effective elimination of infection and the prevention of reinfection. In this review, the term 'Smart RCT' is used as a conceptual framework that integrates digital intelligence, engineering-based operative assistance, and material-based biological functions. We systematically synthesise contemporary evidence on the development and application of smart technologies across the major stages of RCT. By critically evaluating both the potential and current limitations of these technologies, this review aims to provide an evidence-based perspective on the integration of intelligent advances into contemporary endodontic decision-making and clinical practice.
AIM:This case report presents the 24-month outcomes of regenerative endodontic procedures (REPs) combined with apical microsurgery in a mature permanent tooth with a blunderbuss open apex and chronic apical periodontitis. A multimodal assessment protocol integrating laser Doppler flowmetry (LDF), magnetic resonance imaging (MRI) and cone beam computed tomography (CBCT) volumetric analysis was employed to comprehensively evaluate the therapeutic efficacy of this combined approach. SUMMARY:A 25-year-old female patient presented with a mandibular right canine diagnosed with pulp necrosis, a blunderbuss open apex and a large periapical radiolucency. Despite multiple sessions of chemomechanical disinfection, persistent sanguopurulent intracanal exudate was observed, indicating an extraradicular infection. Apical microsurgery was therefore performed to eradicate the extraradicular biofilm, after which autologous CGF was compacted into both the pulp space and the apical surgical site, followed by coronal sealing with iRoot BP Plus. This combined approach aimed to promote tissue regeneration within the canal and concurrently facilitate periapical bone healing. Over a 24-month follow-up period, complete periapical osseous healing was confirmed at 12 months. At 18 and 24 months, LDF demonstrated that blood perfusion in the treated tooth was comparable to that of the contralateral healthy tooth, and MRI revealed continuous homogeneous pulp-like signal within the intraradicular tissue. The tooth also regained positive responses to cold and electric pulp testing from 6 months postoperatively, indicating recovery of sensory nerve fibre function rather than definitive pulp vitality. Concurrent CBCT volumetric analysis documented a progressive reduction in pulp space volume of 9.88% over 24 months, suggesting hard tissue deposition; however, the histological nature of this tissue remains undetermined.
BACKGROUND:The bioactive molecules released from dentine are key to stem-cell recruitment, proliferation and differentiation in regenerative endodontics. However, there is limited and conflicting information regarding current and potential agents for releasing dentine bioactive molecules for regenerative endodontic procedures. OBJECTIVES:To answer a focused and PICOS-designed question: are there any available experimental agents [Intervention (I)] comparable to EDTA [Comparison/Control (C)] in releasing bioactive molecules [Outcome (O)] from dentine [Population (P)] for regenerative endodontic procedures? METHOD:A systematic search was conducted (PubMed, Web of Science, Scopus, Medline [Ovid], Embase [Ovid], ProQuest Central, Google Scholar and citation searching: backwards and forwards), from inception until August 2025. The selection process followed the PICOS model to define inclusion and exclusion criteria. Original studies investigating experimental agents for the release of bioactive molecules from the dentine, compared with EDTA, were included. The risk of bias was strictly assessed using the QUIN tool for in vitro dental studies. Qualitative analysis was performed, while meta-analysis was not possible. RESULTS:Out of the 1364 studies screened, 32 were included. These studies from 2000 to 2025 investigated 23 experimental agents in comparison with EDTA. All were in vitro; of the studies, two had a low risk of bias, 25 had a moderate risk (11 with the minimum score) and five had a high risk of bias. A lack of methodological rigour was identified in approximately 80% of the included studies, including omissions of pH measurements for experimental groups, deficiencies in data assessment or normalisation to account for potential inter-sample variability and deficiencies in validation against detection limits. The qualitative analysis indicated that 9% etidronic acid (known as HEBP), 1% phytic acid, chitosan and 10% citric acid released TGF-β1 and/or VEGF levels as effectively as both 10% and 17% EDTA. CONCLUSION:Qualitative analysis suggested that 9% etidronic acid (HEBP), 1% phytic acid, chitosan and 10% citric acid might serve as alternatives to 17% EDTA use for releasing bioactive molecules from dentine. However, the methodological issues and lack of robust evidence limit the strength and comparability of the findings, highlighting the need for further well-designed and rigorous studies before clinical translation. REGISTRATION:Open Science Framework (OSF) registries: 10.17605/OSF.IO/SPDUQ (Registration DOI: https://doi.org/10.17605/OSF.IO/SPDUQ).
AIM:This multicenter cross-sectional study evaluated the prevalence and variables statistically associated with primary and post-treatment apical periodontitis (AP) in subjects from eight Hispanic American countries. METHODOLOGY:Digital panoramic radiographs from subjects living in Argentina, Colombia, Ecuador, Guatemala, Mexico, Dominican Republic, Uruguay and Venezuela were analyzed. Teeth were evaluated for diverse factors, including the periapical status and presence of root canal treatment, caries, coronal restoration, intraradicular post, root resorption and periodontal involvement. Quality of root canal treatment and coronal restorations was also recorded. Associations between these diverse variables and AP were evaluated using chi-square tests and multivariable mixed-effects logistic regression with a random intercept for patient to account for within-patient clustering of teeth. RESULTS:Overall, 11 850 subjects (294 662 teeth) were included; 51.5% of the subjects and 5.5% of the examined teeth had AP. Ecuador (62%) and Argentina (61%) had the highest AP prevalence per subject, whereas Mexico had the lowest (37%). Intermediate values were observed in Venezuela (57%), Guatemala (57%), Colombia (47%), Dominican Republic (46%) and Uruguay (45%). In general, 43% of the subjects had at least one root canal-treated tooth. Primary and post-treatment AP were observed in 3% and 42% of the teeth, respectively. Of the teeth with primary AP, 51% showed coronal restorations, and 32% had caries. Post-treatment AP was significantly associated with inadequate root canal fillings, inadequate coronal restorations and inadequate intraradicular posts (p < 0.05). CONCLUSIONS:The prevalence of AP in the Hispanic American countries evaluated was high, affecting nearly half of the population. Post-treatment AP was highly prevalent and predominantly linked to inadequate root canal fillings, deficient or absent coronal restorations and intraradicular posts. These findings emphasize the importance of strengthening caries prevention strategies and improving the quality of endodontic and restorative care to reduce the burden of apical periodontitis in these regions.
BACKGROUND:Calcium silicate sealers (CSS) have become the dominant approach to root canal obturation in many specialist practices, yet evidence on their performance in nonsurgical retreatment is sparse and CBCT-based assessment remains uncommon. The behaviour of a CSS-based retreatment protocol under three-dimensional assessment is therefore poorly characterised. AIM:To evaluate the clinical and radiographic outcomes of nonsurgical retreatment with a calcium silicate sealer using both periapical (PAI) and CBCT (CBCT-PAI) indices, and to identify factors associated with CBCT-assessed success. METHODOLOGY:One hundred and thirty-six previously root canal treated teeth in 97 patients were enrolled at Jaber Al-Ahmed Dental Center, Kuwait, between March 2023 and December 2024. A single endodontist performed retreatment using a standardised sealer-based obturation protocol with a calcium silicate sealer (CeraSeal). Teeth were re-examined clinically at 12-24 months. Two calibrated specialists independently scored periapical radiographs (PAI) and small-field-of-view CBCT (CBCT-PAI), classifying each tooth as Healed, Healing or Diseased under both systems to yield four endpoints (PAI-loose, PAI-strict, CBCT-loose, CBCT-strict). The CBCT endpoints were primary and PAI endpoints descriptive. Multivariable analysis used Hosmer-Lemeshow purposeful selection with generalised estimating equations (CBCT-strict) and Firth's penalised logistic regression (CBCT-loose). RESULTS:Of 136 enrolled teeth, 118 in 80 patients were re-examined (tooth-level recall 86.8%, patient-level recall 82.5%, mean follow-up 13.9 months). Success rates were 93.2% (PAI-loose), 89.0% (CBCT-loose), 83.1% (PAI-strict) and 64.4% (CBCT-strict). Each one-point increase in pre-operative CBCT-PAI reduced the adjusted odds of CBCT-strict success (adjusted OR 0.57, 95% CI 0.41-0.81, p = 0.001). Non-molar teeth had higher odds of CBCT-loose success than molars (OR 4.69, 95% CI 1.30-25.01, p = 0.017). A pre-specified sensitivity analysis recoding pre-operative CBCT-PAI as absence (≤ 1) versus presence (≥ 2) of periapical radiolucency confirmed the CBCT-strict finding. CONCLUSIONS:In a cohort weighted toward large pre-operative lesions (65% at CBCT-PAI ≥ 4), nonsurgical retreatment with a calcium silicate sealer produced outcomes at the upper end of the pooled retreatment literature under both PAI- and CBCT-based assessment at 12 to 24 months. Pre-operative lesion size was the dominant predictor of complete healing (CBCT-strict), while tooth type was the only independent predictor of CBCT-loose success. TRIAL REGISTRATION:This study was registered on ClinicalTrials.gov (identifier NCT05714384).
OBJECTIVES:Mechanical and/or microbial stimuli can prompt extracellular ATP release in many cell types, where it acts as an inflammatory mediator to amplify pain signals and inflammation. This study aimed to investigate the synergistic effects of microbial and/or mechanical stimulation on ATP and cytokine release from dental pulp cells (DPCs) and to determine if the inflammatory signalling identified was dependent on ATP acting via the purinergic receptor, P2X3. METHODS:DPCs were prepared from sound third molars using explant culture method. P2X3 protein expression and functionality in DPCs were investigated by immunostaining and calcium mobilisation assays using the P2X3 agonist αβmeATP and antagonist AF-353. ATP or interleukin-6 (IL-6) release from DPCs treated with lipoteichoic acid (LTA) and fluid shear stress or stretch was measured using the ATPlite luciferase assay (PerkinElmer) or ELISA (R&D Systems), respectively. To assess the role of P2X3 activation in IL-6 release, the P2X3 antagonist AF-353 was included in ELISA experiments. Data were checked for normality and analysed by Mann-Whitney test for two-group comparisons and Kruskal-Wallis or ANOVA test with Dunn's or Dunnett's multiple comparisons test where appropriate for multiple-group comparisons. RESULTS:The DPCs expressed functional P2X3 receptors. The cells' response to αβmeATP was significantly inhibited by AF-353 (p < 0.0001). Increased ATP and IL-6 release were observed following co-stimulation with LTA and fluid shear stress (p < 0.01, p < 0.05) or LTA and stretch (p < 0.05). The addition of AF-353 reduced IL-6 release by 34% and 36% (p < 0.05) in DPCs co-stimulated with LTA and fluid shear stress or stretch, respectively. CONCLUSION:This study demonstrates that the combined bacterial mimetic and mechanical stimulation of DPCs significantly enhances ATP and IL-6 release. The inhibition of IL-6 release by the P2X3 antagonist AF-353 indicates the importance of P2X3 receptor activation in this process. These findings offer insights into the molecular mechanisms of dental pulp inflammation and potential therapeutic targets.
AIM:To introduce the concept of segmental intentional replantation (SIR) and to evaluate its clinical feasibility in the management of large periapical cystic lesions. SUMMARY:This retrospective case series evaluated eight teeth in seven patients (3 males and 4 females; mean age, 53.0 ± 14.6 years) presenting with persistent large periapical cystic lesions that were managed using the SIR procedure. All teeth were successfully replanted with a mean extraoral time of 16 min and 50 s. Following the procedure, all replanted tooth-bone complexes were clinically retained without major complications, maintaining stable probing depths of ≤ 3 mm. Clinical stability assessments using Periotest values (PTVs) and Implant Stability Values (ISVs) indicated functional stability of the replanted teeth without clinical or radiographic signs of ankylosis. Furthermore, radiographic analyses using periapical radiographs and cone-beam computed tomography (CBCT) demonstrated minimal horizontal bone-width alteration and stable marginal bone levels, showing a mean marginal bone-level change of 0.02 mm during the follow-up period.
AIM:To evaluate CD68 and F4/80 glycoproteins in the worsening of apical periodontitis (AP) and liver fibrosis (LF) in Wistar rats. METHODOLOGY:Thirty-two Wistar rats were distributed in the following groups (n = 8): C-control; AP-apical periodontitis; LF-liver fibrosis; APLF-AP and LF. LF was induced by carbon tetrachloride administration for 8 weeks and surgical bile duct ligation; AP was induced by the exposure of the dental pulp to the oral environment for 30 days. Mandibles and livers were removed after euthanasia. The histological and immunohistochemical analysis of CD68 and F4/80 glycoproteins were performed. Two-way ANOVA test was used for statistical analysis (p < 0.05). RESULTS:The livers of the LF and APLF groups showed generalised portal inflammatory infiltrate and collagen fibres, confirming the presence of LF. The immunohistochemical analysis in the liver revealed a greater number of CD68 and F4/80 in the APLF group when compared with AP (p < 0.05). Histopathological analysis in the mandibles of the AP and APLF groups showed areas of necrosis comprising the entire dental pulp and periapical tissue surrounded by inflammatory infiltrate. Immunohistochemical analysis showed greater immunolabelling for CD68 and F4/80 in the APLF group than in the AP group (p < 0.05). CONCLUSION:CD68 and F4/80 glycoproteins exhibit inflammatory synergy between apical periodontitis and liver fibrosis, increasing macrophage numbers in the inflammatory processes of both diseases.
AIM:To compare four rotary nickel-titanium (NiTi) file systems (Endostar E3 Azure, Endostar E3, VDW.ROTATE, and Mtwo) using a multimethod approach to evaluate their mechanical and metallurgical properties. MATERIALS AND METHODS:Endostar E3 Azure, Endostar E3, VDW.ROTATE, and Mtwo (all size 25/0.06 with an S-shaped cross-section; 52 instruments per system) were evaluated. Mechanical performance was assessed through static and dynamic cyclic fatigue tests (each treated as a separate and independent test model) together with torsional resistance, bending and buckling tests; the number of cycles to fracture (NCF) was used to compare cyclic fatigue resistance across systems operated at different rotational speeds. Metallurgical characterisation included scanning electron microscopy (SEM) for fractographic and surface analysis, energy-dispersive X-ray spectroscopy (EDS) for surface elemental composition, and differential scanning calorimetry (DSC) for phase-transformation temperatures. RESULTS:Endostar E3 Azure and VDW.ROTATE recorded the highest cyclic fatigue resistance and did not differ from each other within the fatigue models; both surpassed the conventional-alloy instruments (p < 0.05). In the static model, Endostar E3 and Mtwo did not differ from each other (p > 0.05). Endostar E3 yielded the highest maximum torque (0.63 ± 0.01 Ncm), bending force (13.84 ± 1.79 gF) and buckling load (14.37 ± 4.13 gF; p < 0.05), whereas VDW.ROTATE showed the greatest angular deflection (577.03° ± 98.59°; p < 0.05). DSC revealed R-phase-mediated multi-step transformations in the heat-treated files, with austenite finish (Af) temperatures near body temperature; the conventional-alloy files exhibited a single low-intensity peak consistent with a wholly austenitic state. EDS detected surface oxygen on the thermomechanically processed files, indicating the presence of a TiO2 layer. CONCLUSIONS:Thermomechanically processed systems exhibited greater flexibility and longer fatigue life, whereas conventional NiTi instruments demonstrated higher rigidity and torque capacity. DSC-based phase characterisation was consistent with the divergent mechanical outcomes observed among groups and offered a plausible metallurgical explanation, although the contributions of alloy processing and instrument design could not be separated within the present study design.
