WP Front Range Dental http://feed.informer.com/digests/RP4HYZUCRE/feeder WP Front Range Dental Respective post owners and feed distributors Tue, 17 May 2016 00:58:54 -0700 Feed Informer http://feed.informer.com/ Restoration's Longevity in Endodontically Treated Teeth: A Machine Learning Survival Analysis From Randomised Clinical Trials https://onlinelibrary.wiley.com/doi/10.1111/iej.70048?af=R International Endodontic Journal urn:uuid:48e55a4f-3b14-c787-1485-2ac16135c5ae Wed, 15 Oct 2025 08:51:41 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This prognostic study aims to develop a machine learning (ML) survival model for estimating the longevity (success and survival rate) of restorations in endodontically treated teeth (ETT).</p> <h2>Methodology</h2> <p>Data were consolidated from four controlled clinical trials conducted in the Netherlands and Brazil, involving 424 patients and 618 restorations with up to 17 years of follow-up. The evaluated predictive models included Gradient Boosting Survival, Random Survival Forests and Survival Support Vector Machine. The dataset was split into 70% for training and 30% for testing. Hyperparameter tuning was optimised via 10-fold cross-validation with 50 iterations using hyperopt. Performance was assessed through the time-dependent area under the ROC curve (AUC), concordance index (C-index), inverse probability of censoring weights (IPCW C-index) and time-dependent Brier score.</p> <h2>Results</h2> <p>The Gradient Boosting Survival model achieved the highest AUC mean (0.83, 95% confidence interval [CI], 0.81–0.78), C-index (0.80), IPCW C-index (0.78) and Brier score (0.06) for survival rate predictions, maintaining predictive stability over time. For success rate, the Random Survival Forest model outperformed others (AUC = 0.73, 95% CI [0.70–0.75]), C-index (0.66), IPCW C-index (0.64) and Brier score (0.14). SHAP analysis identified patient age and tooth type as having the highest variable importance for survival, while the dentist's experience was critical for success outcomes. Fairness analysis revealed performance disparities across sexes and countries in the models.</p> <h2>Conclusions</h2> <p>The models demonstrated high predictive performance, mainly in survival rate prediction. ML models show promise for developing a robust, data-driven framework to evaluate success and survival outcomes in ETT.</p> Minimally Invasive Vertical Incision Subperiosteal Tunnelling Technique for Targeted Endodontic Surgery: Technical Overview and a Case Report https://onlinelibrary.wiley.com/doi/10.1111/iej.70014?af=R International Endodontic Journal urn:uuid:f3ffea6f-e6f4-fb45-8a6d-59fc2a8ec2c4 Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1799-1805, November 2025. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This technical review and case report describes the Minimally Invasive Vertical Incision Subperiosteal Technique (MIVIST) for use in specific targeted endodontic surgical cases.</p> <h2>Summary</h2> <p>The proposed MIVIST technique includes a vertical incision along with auxiliary vertical release incisions to enhance soft tissue healing during targeted endodontic surgery for teeth with small periapical lesions. The technique is described in a case report where a patient presented with persistent periapical periodontitis associated with a previously root canal treated tooth (#15). Based on the preoperative intraoral scan and cone beam computed tomography (CBCT) three-dimensional surgical guides were printed. A vertical main incision and additional release incisions were placed in the buccal mucosa of tooth 15 over healthy bone, with subperiosteal tunnelling then being performed to provide adequate access to the lesion and root apex. A guided osteotomy was carried out using the surgical template, followed by root-end cavity preparation and filling. The patient was followed up over 24 months, when excellent soft tissue healing as well as radiographic healing was apparent.</p> Issue Information https://onlinelibrary.wiley.com/doi/10.1111/iej.14095?af=R International Endodontic Journal urn:uuid:aa077e9a-e60e-b616-eb94-f91039d43710 Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1669-1669, November 2025. Efficacy of Combined Versus Supplementary Injection Techniques With Inferior Alveolar Nerve Block for Mandibular Molars With Symptomatic Irreversible Pulpitis: A Systematic Review and Network Meta‐Analysis https://onlinelibrary.wiley.com/doi/10.1111/iej.70007?af=R International Endodontic Journal urn:uuid:d5eff1f3-c8ac-d974-5ee4-3768b8372b2e Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1681-1710, November 2025. <h2>ABSTRACT</h2> <h2>Background</h2> <p>Achieving effective anaesthesia in mandibular molars with symptomatic irreversible pulpitis is challenging. Various strategies involving the inferior alveolar nerve block (IANB) have been investigated, such as supplementing with additional injections after IANB failure (SUPP) or combining injections with IANB as primary injections (COMB). However, studies directly comparing SUPP and COMB are still lacking.</p> <h2>Objectives</h2> <p>This study aims to assess and compare the anaesthetic effectiveness of different IANB strategies—SUPP and COMB—in mandibular posterior teeth with symptomatic irreversible pulpitis using a systematic review and network meta-analysis.</p> <h2>Method</h2> <p>A comprehensive search was conducted in the PubMed, Embase, Cochrane Library, CINAHL and Scopus databases to identify relevant studies up to October 2024. Eligible randomised clinical trials (RCTs) were analysed using pairwise meta-analysis and network meta-analysis with a random-effects model to estimate treatment effects. Results were reported as risk ratios (RRs) with 95% confidence intervals (CIs) and surface under the cumulative ranking curve (SUCRA) values. The quality of the evidence was assessed using the CINeMA (Confidence in network meta-analysis) software (University of Bern, Bern, Switzerland).</p> <h2>Results</h2> <p>A total of 28 studies involving five interventions were identified. Compared with IANB alone, both SUPP (RR = 2.02; 95% CI: 1.55–2.30; SUCRA: 85.1%) and COMB (RR = 1.86; 95% CI: 1.50–2.30; SUCRA: 64.9%) significantly improved anaesthetic success. However, there was no significant difference in effectiveness between SUPP and COMB.</p> <h2>Conclusion</h2> <p>The quality of evidence ranging from low to high suggests that both SUPP and COMB are comparable in anaesthetic efficacy during endodontic treatment of mandibular molars with symptomatic irreversible pulpitis. However, both SUPP and COMB strategies showed significantly superior effectiveness compared to IANB alone.</p> Impact of Endodontic Disease on Oral Health‐Related Quality of Life in the Elderly https://onlinelibrary.wiley.com/doi/10.1111/iej.70008?af=R International Endodontic Journal urn:uuid:904f0471-a351-050b-3499-093d6501bbe9 Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1711-1724, November 2025. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>The silver tsunami poses a global healthcare challenge, and this study aimed to assess the impact of endodontic disease on oral health-related quality of life (OHRQOL) in an elderly population who received non-surgical root canal treatment (NSRCT). The appropriateness of the Oral Health Impact Profile (OHIP-17) and General Oral Health Assessment Index (GOHAI) as OHRQOL assessment tools for this population was also assessed.</p> <h2>Methodology</h2> <p>Patients aged ≥ 65 years who received NSRCT were recruited. OHRQOL assessments were conducted using OHIP-17, GOHAI and an oral health perception questionnaire. The severity of impact was assessed by summing the numeric response codes for all questions, producing a total score for each participant potentially ranging from 0 to 68 for OHIP-17 and 0 to 48 for GOHAI, with higher scores indicating poorer OHRQOL. Potential influencing factors for OHRQOL scores were investigated. Internal consistency, concurrent validity and discriminant validity of both tools were evaluated.</p> <h2>Results</h2> <p>One hundred and twenty-two patients were recruited. The mean total OHIP-17 and GOHAI scores were 16.35 ± 11.81 (maximum possible score = 68) and 16.85 ± 7.04 (maximum possible score = 48) respectively. The percentage of patients reporting no impact was lower with GOHAI (0.8%) than OHIP-17 (9.8%). Multivariate analyses showed that higher OHRQOL scores were significantly associated with higher levels of education, full/part-time employment and more teeth that received NSRCT. Internal consistency was high for both tools. Concurrent validity assessment demonstrated a significant association of satisfaction with oral health for GOHAI, and perceived importance of keeping one's own teeth and perceived oral health for both OHIP-17 and GOHAI. Neither tool significantly correlated patient-reported impact with clinicians' assessment of oral health.</p> <h2>Conclusions</h2> <p>In elderly patients who received NSRCT, OHRQOL is negatively associated with higher education level, being employed, and more teeth that received NSRCT. GOHAI appears more successful than OHIP-17 in detecting the impact of endodontic disease on OHRQOL.</p> Progranulin (PGRN) Facilitates Anti‐Inflammation and Pulpitis Repair In Vivo and In Vitro Through TNFR2/14‐3‐3ε Signalling Complex https://onlinelibrary.wiley.com/doi/10.1111/iej.70000?af=R International Endodontic Journal urn:uuid:53e2bcda-513a-5138-b3f9-f8b268511f2c Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1725-1737, November 2025. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To investigate the role and mechanism of progranulin (PGRN) in reparative dentinogenesis and inflammation control for rat pulpitis and inflammatory human dental pulp stem cells (hDPSCs).</p> <h2>Methodology</h2> <p>Eight-week-old male Wistar rats with irreversible pulpitis were treated with pulpotomy and divided into five groups: No treatment; Control; iRoot BP plus (BP); GelMA and recombinant human PGRN (rhPGRN) + GelMA (rhPGRN). Micro-computed tomography (Micro-CT) scans and histological and immunohistochemical staining were conducted to evaluate rhPGRN' anti-inflammation and pro-healing properties. The effects of rhPGRN on hDPSC inflammatory response, proliferation and dentinogenic differentiation and potential signalling pathways were assessed through CCK-8, alkaline phosphatase (ALP) staining, alizarin red staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and western blotting.</p> <h2>Results</h2> <p>In vivo, PGRN expression obviously increased in both the Control and GelMA groups compared to healthy pulp (<i>p</i> &lt; 0.05). The BP and rhPGRN groups showed a significant decrease in inflammatory scores and expression of M1 macrophage markers CD86 and tumour necrosis factor alpha (TNF-α) while increasing M2 markers CD206 and interleukin 10 (IL-10) compared with the controls (<i>p</i> &lt; 0.05). Enhanced dentine bridge formation and dentine sialophosphoprotein (DSPP) expression were observed in the BP and rhPGRN groups versus the controls (<i>p</i> &lt; 0.05). Moreover, the rhPGRN group presented higher expressions of CD206, IL-10 and DSPP than the BP group (<i>p</i> &lt; 0.05). In vitro, PGRN expression significantly increased in lipopolysaccharide (LPS)-stimulated hDPSCs (<i>p</i> &lt; 0.05). rhPGRN significantly reduced the release of TNF-α, interleukin 1 beta (IL-1β) and IL-6 in LPS-stimulated hDPSCs and enhanced ALP activity, mineralized nodule formation and expression of ALP, Runt-related transcription factor 2 (RUNX2) and DSPP in LPS-stimulated or unstimulated hDPSCs (<i>p</i> &lt; 0.05). Mechanistically, co-immunoprecipitation showed that PGRN bound to tumour necrosis factor receptor-2 (TNFR2), interacting with 14-3-3 epsilon (14-3-3ε) in hDPSCs. PGRN significantly inhibited LPS-activated phosphorylation of NF-κB/p65 and its nuclear translocation, and the use of a TNFR2 neutralising antibody or the 14-3-3 protein inhibitor R18 reversed these effects (<i>p</i> &lt; 0.05).</p> <h2>Conclusion</h2> <p>These findings suggest that PGRN plays a crucial role in anti-inflammation, immunomodulation and reparative dentinogenesis in rat pulpitis via the TNFR2/14-3-3ε-NF-κB pathway, highlighting its potential as a strategy for vital pulp therapy.</p> Endoplasmic Reticulum Stress Inhibits the Neuronal Differentiation of Human Stem Cells From Apical Papillae by Attenuating the Activity of ERK–IRE1α Axis In Vitro https://onlinelibrary.wiley.com/doi/10.1111/iej.70003?af=R International Endodontic Journal urn:uuid:302b818d-f7a8-ce6e-90a0-33c2f1551c77 Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1738-1750, November 2025. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>Stem cells from apical papillae (SCAPs) are promising seed cells for angiogenesis, neurogenesis and dental pulp regeneration, which are contingent upon endoplasmic reticulum (ER) homeostasis. Due to the narrow anatomical structure of the root canal system and slow ingrowth of vasculatures, the presence of hypoxia and nutrient-deficient microenvironment within the sterilised root canal space may induce ER stress in the transplanted cells and affect their differentiation into neural lineages. This study aimed to investigate the role of ER stress in the neuronal differentiation of human SCAPs and its underlying mechanisms.</p> <h2>Methodology</h2> <p>Thapsigargin (TG) was employed to induce ER stress in SCAPs. ER Ca<sup>2+</sup> level was quantified by Mag-Fluo 4 AM. Quantitative real-time PCR (qRT-PCR) and western blot were conducted to detect ER stress markers. SCAPs, with or without ER stress, were guided towards neuronal differentiation. We measured the expression of neuronal markers and the activation of the extracellular signal-regulated kinase (ERK1/2) and the unfolded protein response (UPR) signalling. Immunofluorescence staining was applied to observe SCAP-derived neuron-like cells. The kinetic Ca<sup>2+</sup> influx of SCAP-derived neuron-like cells was monitored using a fluorescence microscope. SCH772984 and MKC8866 were used to selectively inhibit ERK1/2 and inositol-requiring enzyme 1α (IRE1α) activation, respectively. Statistical analyses were conducted using the GraphPad Prism 10 software.</p> <h2>Results</h2> <p>After TG stimulation, ER Ca<sup>2+</sup> levels in all TG-treated SCAP groups were markedly reduced, the ER stress markers were significantly upregulated and UPR activation was found. Following neuronal induction, ER stress induced by 20 nM TG did not inhibit SCAP neuronal differentiation. However, ER stress induced by 40 or 80 nM TG significantly inhibited neuronal marker expression, neurite outgrowth and Ca<sup>2+</sup> influx in SCAP-derived neuron-like cells. The phosphorylated ERK1/2 decreased during neuronal differentiation, along with the reduction of phosphorylated-IRE1α (p-IRE1α). Inhibition of ERK1/2 activation led to neuronal marker protein reduction, neurite outgrowth restraint and p-IRE1α decrease. Selective inhibition of IRE1α activity suppressed NeuN expression and neurite outgrowth.</p> <h2>Conclusion</h2> <p>Severe ER stress inhibits the neuronal differentiation of SCAPs via decreasing ERK1/2 and IRE1α activity, whereas ER stress at an appropriate level is essential for the neuronal differentiation of SCAPs.</p> Mechanical and Metallurgical In Vitro Evaluation of Electropolished Versus Non‐Electropolished Rotary and Reciprocating Instruments https://onlinelibrary.wiley.com/doi/10.1111/iej.70009?af=R International Endodontic Journal urn:uuid:e344bf63-7616-02c8-f6a3-d17b2e5c89e9 Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1774-1782, November 2025. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To evaluate the effect of electropolishing on the mechanical properties of One RECI and One Curve mini nickel-titanium (NiTi) instruments by comparing electropolished and non-electropolished versions of each instrument type.</p> <h2>Methodology</h2> <p>Electropolished and non-electropolished One RECI (reciprocating) and One Curve mini (rotary) NiTi instruments, all manufactured with identical geometry and heat treatment, were evaluated. Instrument design was analysed by light microscopy and scanning electron microscopy, while metallurgical characterisation was performed using energy-dispersive X-ray spectroscopy (EDS) and differential scanning calorimetry (DSC). Mechanical performance was assessed through torsional resistance, bending and buckling load, surface microhardness, and cutting efficiency. Statistical comparisons were performed using the independent samples t-test or the Mann–Whitney <i>U</i>-test, with significance set at <i>p</i> &lt; 0.05.</p> <h2>Results</h2> <p>Design and metallurgical analyses confirmed that electropolished and non-electropolished instruments within each group were equivalent in terms of geometry, cross-sectional design, tip configuration, elemental composition, and phase transformation temperatures. Electropolishing significantly enhanced flexibility in both instrument types, as indicated by reduced bending loads and lower buckling resistance (<i>p</i> &lt; 0.05). However, torsional strength was significantly reduced in the electropolished One RECI instruments, reflected by lower maximum torque and angle of rotation prior to fracture (<i>p</i> &lt; 0.05). No significant torsional differences were observed in the One Curve mini group (<i>p</i> &gt; 0.05). Surface microhardness and cutting efficiency remained unaffected by electropolishing in both systems (<i>p</i> &gt; 0.05).</p> <h2>Conclusions</h2> <p>Electropolishing improved the flexibility of both One RECI and One Curve mini NiTi instruments without compromising their surface microhardness or cutting efficiency. However, its impact on torsional resistance was system-dependent, resulting in reduced strength only in the reciprocating One RECI instruments.</p> Characterising 12 NiTi Reciprocating Systems: An Integrative Laboratorial Analysis of Design, Mechanics, Metallurgy, Fluid Dynamics and Finite Element Analysis https://onlinelibrary.wiley.com/doi/10.1111/iej.70010?af=R International Endodontic Journal urn:uuid:56aee48c-7cdb-29c1-1b6a-b206d5e87ded Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1783-1798, November 2025. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To comprehensively compare 12 nickel–titanium (NiTi) reciprocating single-file systems from eight manufacturers by integrating geometric, mechanical, metallurgical and <i>in silico</i> analyses.</p> <h2>Methodology</h2> <p>A total of 276 NiTi reciprocating instruments, representing 12 types across 8 brands, were selected, including Easy-File Flex Regular 25, EdgeOne Fire Primary, Flash 25.06vt, One Files R25 and Blue R25, One RECI N25, Perfect RC R25 (Blue, Gold and Silver), Reciproc R25 (Blue and M-Wire) and WaveOne Gold Primary. They were evaluated using stereomicroscopy, scanning electron microscopy, 3D optical scanning, energy-dispersive X-ray spectroscopy and differential scanning calorimetry to assess design and metallurgical properties. Mechanical performance was tested via buckling resistance and microhardness. A micro-CT-based premolar model was virtually prepared for each instrument to simulate canal shaping. Computational fluid dynamics (CFD) assessed irrigant penetration, wall shear stress and apical pressure. Finite element analysis (FEA) evaluated stress distribution in prepared roots. Data were analysed using the Shapiro–Wilk test for normality and the Kruskal–Wallis test for group comparisons (<i>p</i> &lt; 0.05).</p> <h2>Results</h2> <p>The systems differed considerably in spiral density, cross-sectional design, size, volume and phase transformation temperatures. Instruments with larger apical cores (One Files and Reciproc M-Wire) and austenitic-phase dominance (Perfect RC Silver and One Files) showed greater buckling strength. Files with martensitic phases (Perfect RC Gold, WaveOne Gold and One Files Blue) or hybrid cross-sections (One RECI and Flash) were more flexible. CFD revealed that conservative shaping (Easy-File Flex, EdgeOne Fire, One RECI, WaveOne Gold) increased wall shear stress but reduced apical irrigant exchange. FEA showed similar stress patterns across all groups, with lower stress in restored roots.</p> <h2>Conclusions</h2> <p>Substantial variation exists among current NiTi reciprocating systems in terms of design, mechanics, fluid dynamics and metallurgy. Instruments with large cores and austenitic-phase structure provide superior buckling resistance. Conservative shaping improves shear stress but limits apical cleaning. Root stress remained consistent across systems. These findings highlight the importance of optimising instrument design and clinical protocols to balance shaping efficacy and irrigant delivery.</p> Multispecies Biofilms Treated With Endodontic Sealers or Calcium Hydroxide: Antimicrobial Activity and Changes in Community Composition https://onlinelibrary.wiley.com/doi/10.1111/iej.70015?af=R International Endodontic Journal urn:uuid:9afe2954-c086-0239-55ed-6eb6690526a2 Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1764-1773, November 2025. <h2>ABSTRACT</h2> <h2>Introduction</h2> <p>To evaluate the antimicrobial activity and changes in community composition in biofilms treated with two root canal sealers or calcium hydroxide.</p> <h2>Material and Methods</h2> <p>Forty-nine extracted bovine dentine cylinders were inoculated with subgingival dental plaque for 2 weeks in a CDC biofilm reactor. Three treatment groups were assigned: AH Plus, BC Sealer, and calcium hydroxide. Propylene glycol inert vehicle (PG) and untreated contaminated samples were used as controls. The infected root canal space was in direct contact with the materials for 7 days under anaerobic incubation. Anaerobic culture (colony forming units, CFU), quantification PCR (qPCR), and next generation sequencing were used to assess the effect of each material. Differences in the number of molecules (qPCR), CFU, and abundances of genera were evaluated using the Kruskal–Wallis test. The Shannon and Chao1 indices were used to measure alpha diversity. Differences in community composition were evaluated using non-parametric analysis of similarity (ANOSIM).</p> <h2>Results</h2> <p>The CFU, Shannon, and Chao1 indices revealed significant differences between BC Sealer, AH Plus, and calcium hydroxide groups versus the untreated control group and PG (<i>p</i> &lt; 0.003). Calcium hydroxide and BC Sealer significantly reduced the qPCR values compared to the control group and PG. The biofilm composition (98.5%) was primarily composed of <i>Peptostreptococcus</i>, <i>Streptococcus</i>, <i>Parvimonas</i>, <i>Fusobacterium</i>, <i>Veillonela</i>, <i>Mogibacterium</i>, <i>Lancefieldella</i>, <i>Eubacterium</i>, <i>Slackia</i>, and <i>Prevotella</i>. Significant differences in overall community composition and beta diversity between untreated controls and AH Plus were observed (ANOSIM <i>R</i> = 0.674, <i>p</i> &lt; 0.001). <i>Parvimonas</i>, <i>Streptococcus</i>, <i>Eubacterium</i>, and <i>Lancefieldella</i> were not affected by any of the materials tested.</p> <h2>Conclusion</h2> <p>Calcium hydroxide and BC Sealer significantly reduced the viability and the total number of DNA copies. AH Plus sealer reduced the bacterial viability but did not affect the DNA concentration. AH Plus significantly alters overall biofilm community composition compared to other groups. None of the materials tested eliminated the multispecies biofilm completely.</p> Exploring Relationships Within the Microbiome of Root Canal Infections and the Influence of Associated Clinical Parameters https://onlinelibrary.wiley.com/doi/10.1111/iej.70011?af=R International Endodontic Journal urn:uuid:8f10b762-85fb-9ba2-af1c-6677483edf46 Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1751-1763, November 2025. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To identify relationships among bacterial species in endodontic infections, to determine their core microbiome, and associated clinical characteristics.</p> <h2>Methodology</h2> <p>206 patients with endodontic infections and apical periodontitis were assessed for clinical parameters (periapical lesion, symptomatology, sinus tract). Samples from the apical third of roots were obtained before cleaning and shaping root canals, and microbial composition was analysed using 16S rRNA sequencing and HOMINGS. Correlation Network Analysis (CNA) was performed using the R package igraph, and networks were visualised in Cytoscape with centralities determined by CytoHubba. The core microbiome was identified using the R package Microbiome, listing species comprising at least 1% of samples in over 50% of cases.</p> <h2>Results</h2> <p>The endodontic core microbiome included <i>Parvimonas micra</i>, <i>Streptococcus sanguinis</i>, <i>Enterococcus faecalis</i>, <i>Porphyromonas endodontalis</i>, <i>Prevotella nigrescens</i> and <i>Fusobacterium nucleatum</i>. Symptomatic cases had a core microbiome of <i>Bacteroidaceae.G.1. sp oral taxon 272</i> and <i>Haemophilus parainfluenzae</i>. Sinus cases had a core microbiome of <i>Bacteroidaceae.G.1. sp oral taxon 272</i>, <i>Mogibacterium timidum</i>, <i>Peptostreptococcus stomatis</i>, <i>Pseudoramibacter alactolyticus</i> and <i>Rothia dentocariosa</i>. Lesion cases had a core microbiome of <i>Atopobium rimae</i>, <i>Eubacterium.11.G.1. infirmum</i>, <i>Mogibacterium timidum</i> and <i>Pseudoramibacter alactolyticus</i>. Certain taxa like <i>Bacillus clausii</i> and <i>Eubacterium limosum</i> were never detected.</p> <h2>Conclusions</h2> <p>Despite critical gaps in root canal treatment clinical effectiveness, standardisation and understanding of pathogen complexity, our study, utilising next-generation 16S rRNA Sequencing and HOMINGS, provides valuable insights into core microbiome members involved in endodontic infections and their associations with distinct clinical signs and symptoms, offering insights that may guide more precise diagnosis and targeted treatment.</p> A Critical Review of In Vitro Methodologies for Studying Inflammatory Responses in Human Dental Pulp Cell Cultures https://onlinelibrary.wiley.com/doi/10.1111/iej.70004?af=R International Endodontic Journal urn:uuid:0da77289-4787-bd84-225a-13d1c317d366 Mon, 13 Oct 2025 09:03:45 -0700 International Endodontic Journal, Volume 58, Issue 11, Page 1670-1680, November 2025. <h2>ABSTRACT</h2> <h2>Background</h2> <p>The pulp responds to disease and trauma through inflammation which modulates the tooth's ability to instigate healing mechanisms. In vitro human dental pulp cell (HDPC) culture models are widely used to study the tooth's response to pro-inflammatory stimuli.</p> <h2>Objectives</h2> <p>The purpose of this review is to generate a structured appraisal of in vitro research methodologies to study HDPC cultures in a state of inflammation.</p> <h2>Method</h2> <p>In this narrative review the Scopus, PubMed and Google Scholar databases were searched to identify studies reporting the use of HDPC cultures in vitro in inflammation-associated research until December 2024. The dataset initially identified 642 publications, which were manually screened to identify 246 relevant studies for inclusion and methodologically mined for information on: (i) study purpose, (ii) source and characterisation of cells, (iii) pro-inflammatory stimuli used and (iv) assays and markers used to characterise the inflammatory response. The collected data underpinned this review.</p> <h2>Results</h2> <p>Most published studies aimed to characterise HDPC responses to a range of pro-inflammatory stimulants which included bacterial components (lipopolysaccharides [LPS] and lipoteichoic acids [LTA]), cytokines and biomaterials. These stimulations were studied: to characterise their effect in the development of new scaffolds and dental (bio)materials and to mimic the in vivo environment. Various tooth sources were used to establish HDPC cultures, and predominantly, cells were isolated using the pulp tissue explant technique. The most frequently used stimulant and concentrations were LPS at 1 and 10 μg/mL. The time for cell stimulation prior to inflammatory response assay varied from 15 min to 10 days. Inflammatory assessments were performed using quantitative polymerase chain reaction (qPCR), Western Blotting, enzyme-linked immunosorbent assay (ELISA) and high-throughput assays targeting archetypical cytokines and dentinogenic and mineralisation-associated molecules.</p> <h2>Discussion</h2> <p>This review highlights the broad range of experimental conditions used to study HDPC inflammatory responses in vitro and combines these data to identify a framework for a consensus and a more uniform experimental approach.</p> <h2>Conclusion</h2> <p>Standardisation of in vitro experimental conditions to evaluate the pulps response to inflammatory stimuli would enhance research rigour and improve clinical translation to ultimately inform patient treatment and outcomes.</p> The Clinical Impact of the Combination of CBCT and Periapical Radiographs on Endodontic Diagnosis and Treatment Planning—A Retrospective Cohort Study https://onlinelibrary.wiley.com/doi/10.1111/iej.70050?af=R International Endodontic Journal urn:uuid:c9e3b087-b1b9-73a3-e2ad-7691b8178a60 Sun, 12 Oct 2025 10:36:40 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To determine whether the combined use of periapical radiography (PR) and cone beam computed tomography (CBCT) improves agreement among three endodontic experts compared with using either diagnostic tool alone.</p> <h2>Methodology</h2> <p>Sixty clinical records with CBCT scans were selected from cases performed by postgraduate and master's students in endodontics at the University of Barcelona Dental Hospital. Three endodontic experts independently evaluated each case using a standardised questionnaire. Initially, they assessed the PR images. After 4 months, they reassessed the cases using CBCT. One year later, they reviewed both PR and CBCT together. Agreement levels were analysed for pulpal and periradicular diagnoses, treatment recommendations and aetiological assessments.</p> <h2>Results</h2> <p>Inter-observer agreement improved across the study phases, peaking in phase 3—particularly for treatment recommendations. In this final phase, where both PR and CBCT were evaluated together, the agreement rate for pulpal diagnosis was 73.33%, with substantial reliability (<i>κ</i> = 0.67). Periradicular diagnosis showed a 40.00% agreement rate, with moderate inter-observer concordance (<i>κ</i> = 0.44). The lowest agreement was observed in the aetiology category (28.33%), with moderate concordance (<i>κ</i> = 0.50). Agreement on treatment recommendations reached 43.33% (<i>κ</i> = 0.51) and was the only category to show statistically significant differences between phases (<i>p</i> = 0.01). No significant differences were found for pulpal diagnosis (<i>p</i> = 0.39), periradicular diagnosis (<i>p</i> = 0.19) or aetiology (<i>p</i> = 0.36). Intra-observer agreement varied among experts, with some showing lower consistency in their responses when evaluating PR, CBCT and the combination of both, highlighting the influence of imaging modality on clinical decision-making.</p> <h2>Conclusions</h2> <p>The combination of PR and CBCT improved inter-observer agreement across all categories compared to the use of a single imaging modality. However, this improvement reached statistical significance only for treatment recommendations. These findings suggest that, whereas combining PR and CBCT may support more consistent therapeutic decision-making, its impact on diagnostic agreement may vary depending on the specific diagnostic domain.</p> The Impact of Training Dental Students to Use an Artificial Intelligence–Based Platform for Pulp Exposure Prediction Prior to Deep Caries Excavation: A Proof‐of‐Concept Randomised Controlled Trial https://onlinelibrary.wiley.com/doi/10.1111/iej.70046?af=R International Endodontic Journal urn:uuid:e7c159cd-0ae0-49e8-2d02-ca417315b3db Fri, 10 Oct 2025 10:10:35 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This study evaluated the effect of a short, personalised training session on student performance in using an artificial intelligence (AI)-based platform for pulp exposure prediction before caries excavation and determined the required sample size for a further randomised controlled trial (RCT).</p> <h2>Methodology</h2> <p>Undergraduate dental students were randomly assigned to the experimental (training) group and the control (no training) group. The training group received a 1-h training session before undertaking the experiment, focusing on the uses, applications, and drawbacks of AI and carious lesion penetration depth. The theoretical presentation was followed by practical exercises and a quiz to check learning progress. Later, participants in both groups completed an experimental task involving 292 cases. They were asked to predict pulp exposure using an AI-based website. Sample size calculations determined the required sample size, with 80% power and an alpha of 5%.</p> <h2>Results</h2> <p>18 participants were enrolled (9 in each group). The agreement between participants' decisions and AI predictions regarding the presence or absence of pulp exposure (agreeableness with AI) was higher in the training group compared to the control group (0.83 vs. 0.76). The training group had a slightly higher mean F1-score (0.63 vs. 0.62), accuracy (0.69 vs. 0.68), and sensitivity (0.63 vs. 0.59) than the control group. Based on the sample size calculation, at least 31 participants per group are needed for the future RCT.</p> <h2>Conclusions</h2> <p>The results support further investigation of customised training sessions prior to using an AI-based platform to assess their impact on dental students' agreement with AI predictions.</p> <h2>Trial Registration</h2> <p><a target="_blank" title="Link to external resource" href="http://clinicaltrial.gov">ClinicalTrial.gov</a> identifier: NCT05912361</p> Accuracy of Robot‐Guided Access Cavity Preparation in Managing Calcified Canals: An In Vitro Study https://onlinelibrary.wiley.com/doi/10.1111/iej.70049?af=R International Endodontic Journal urn:uuid:21f3afb1-e343-c8b6-1835-005d9049260f Fri, 10 Oct 2025 02:50:00 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To evaluate the accuracy of guided access cavity preparation in calcified canals using a robotic system, compared to static and dynamic guided methods.</p> <h2>Methodology</h2> <p>Three 3D-printed mandibular models presenting with pulp canal obliteration were allocated into three groups for robot, static and dynamic-guided access cavity preparations. The primary outcomes measured were the coronal deviation, apical deviation and angular deviation between the planned and actual paths of access cavity preparation. Additionally, all access cavities were confirmed to determine whether the canal was located. The data were analysed using the one-way analysis of variance (ANOVA), Tukey's post hoc test and multilevel linear regression models. The significance level was set at 0.05.</p> <h2>Results</h2> <p>All canals (<i>n</i> = 12) in the robot-guided and static-guided groups were located. In the dynamic guided group, a total of 10 out of 12 canals were found, with 2 resulting in root perforations. The accuracy of access cavity preparation using a robotic system showed no significant difference compared to the static-guided group (<i>p</i> &gt; 0.05). However, the apical and angular deviation results were significantly lower in the robot-guided group than the dynamic-guided group (<i>p</i> &lt; 0.05).</p> <h2>Conclusions</h2> <p>The robotic system exhibited comparable accuracy to the static guide, whereas it significantly outperformed dynamic navigation in terms of guided access cavity preparation for calcified root canals. However, further clinical studies are needed to confirm these preliminary findings.</p> A Thermosensitive Gel Containing Biodegradable Nanoparticles Carrying Calcium Hydroxide as Antibacterial Intracanal Therapy https://onlinelibrary.wiley.com/doi/10.1111/iej.70032?af=R International Endodontic Journal urn:uuid:ea610a48-086e-b778-705c-baaa3e62d26b Tue, 07 Oct 2025 01:04:01 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To characterise and evaluate mucoadhesive strength and antibacterial properties of a nanotechnological formulation for endodontic disinfection based on biodegradable nanoparticles dispersed in a thermosensitive gel containing calcium hydroxide (Ca(OH)<sub>2</sub>-NPs-gel).</p> <h2>Methodology</h2> <p>Morphology of Ca(OH)<sub>2</sub>-NPs-gel was studied using transmission electron microscopy. Moreover, Ca(OH)<sub>2</sub>-NPs-gel was sterilised using gamma irradiation (25 kGy), and the stability after the sterilisation process was studied by measuring Ca(OH)<sub>2</sub>-NPs-gel average size, polydispersity index, zeta potential and encapsulation efficiency. To assess the ex vivo mucoadhesive strength, extracted single-rooted human teeth were used to measure the force necessary to separate the formulation from the teeth. In addition, the short-time stability of Ca(OH)<sub>2</sub>-NPs-gel was evaluated monthly, analysing entrapment efficacy, backscattering and transmittance of Ca(OH)<sub>2</sub>-NPs-gel stored at different temperatures (4°C, 25°C and 37°C). Furthermore, the antibacterial analysis of Ca(OH)<sub>2</sub>-NPs-gel was performed against <i>Enterococcus faecalis</i> inoculated in extracted human single-root teeth and evaluated by confocal and scanning electron microscopy. Finally, the metabolic activity of bacteria was studied through a resazurin assay to evaluate bacterial survival after treatment.</p> <h2>Results</h2> <p>Ca(OH)<sub>2</sub>-NPs-gel owned a round shape and a smooth surface without particle aggregation. Sterilisation did not induce an alteration in Ca(OH)<sub>2</sub>-NPs-gel physicochemical properties and Ca(OH)<sub>2</sub>-NPs-gel presented a high adhesion strength. In addition, 4°C was the best temperature to store Ca(OH)<sub>2</sub>-NPs-gel. Regarding the antibacterial therapeutic efficacy, Ca(OH)<sub>2</sub>-NPs-gel possesses suitable antibacterial properties, indicating that it efficiently reduces bacterial biofilms.</p> <h2>Conclusion</h2> <p>Calcium hydroxide-loaded PLGA nanoparticles dispersed in a thermosensitive gel have been developed, optimised and characterised, obtaining excellent antibacterial properties and achieving bacterial disinfection levels similar to those of commercial formulations.</p> Assessment of Case Complexity of Root Canal Treatments Using Contemporary Complexity Grading Systems: A Clinical Service Evaluation https://onlinelibrary.wiley.com/doi/10.1111/iej.70039?af=R International Endodontic Journal urn:uuid:4ff54a86-6ab4-0e70-c922-69db88ca1a13 Mon, 06 Oct 2025 04:54:31 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To assess the complexity of root canal treatments allocated to Postgraduate Endodontology trainees at Cardiff University Dental Hospital (CUDH) using the English Clinical Standards for Restorative Dentistry (ECS) in comparison with the Dental Practicality Index (DPI), the EndoApp (EA), and the Endodontic Complexity Assessment Tool (E-CAT).</p> <h2>Material and Methods</h2> <p>Two-hundred-and-one case records were evaluated by two calibrated examiners using each complexity assessment system. Inter-examiner and intra-examiner variability was calculated using Cohen's kappa coefficient. Statistical analyses compared the scores obtained for the same case using the different systems.</p> <h2>Results</h2> <p>Most cases were assigned level 3 complexity using ECS, EA and E-CAT (82%, 92% and 74.1%, respectively), and scores of 3–5 (78.6%) using DPI. EA consistently assigned higher complexity scores compared with ECS and E-CAT. E-CAT assigned lower complexity scores compared with ECS. A statistically significant moderate–substantial level of agreement was demonstrated between E-CAT and ECS (weighted kappa = 0.647 [95% CI: 0.517 to 0.776], <i>p</i> &lt; 0.001). A statistically significant fair level of agreement was demonstrated between EA and ECS (weighted kappa = 0.290 [95% CI: 0.113 to 0.466], <i>p</i> &lt; 0.001) and EA and E-CAT (weighted kappa: 0.385 [95% CI: 0.226 to 0.544], <i>p</i> &lt; 0.001). A statistically significant weak positive correlation was found between DPI and ECS [Spearman's correlation coefficient (<i>r</i> <sub>s</sub>) = 0.202, <i>p</i> = 0.004], DPI and EA (<i>r</i> <sub>s</sub> = 0.344, <i>p</i> &lt; 0.001), and DPI and E-CAT (<i>r</i> <sub>s</sub> = 0.364, <i>p</i> &lt; 0.001). The most common cause of increase in complexity scores was ‘canal negotiability’ for ECS (47%) and the ‘endodontic treatment need’ for DPI (84.1%). The unknown algorithm used by EA and E-CAT prevented the identification of specific factors that contributed to the endodontic treatment complexity.</p> <h2>Conclusion</h2> <p>The majority of cases treated at CUDH were of high complexity. E-CAT assigned slightly lower complexity scores compared with ECS and EA, potentially due to its detailed assessment of factors. A weak positive correlation was found between the complexity grading systems. DPI's broader assessment justifies a cut-off score of 3 for specialist referral due to the increased agreement with ECS, E-CAT and EA at this threshold.</p> From Cells to Animals: Connexin43 Suppression Enhances Autophagic Flux to Restore Odontogenesis in Inflamed Dental Pulp https://onlinelibrary.wiley.com/doi/10.1111/iej.70044?af=R International Endodontic Journal urn:uuid:17ae468d-8e61-31bd-89d4-d039ed7d0a21 Sun, 05 Oct 2025 09:46:43 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>Under certain conditions, infection-induced inflammation may activate reparative processes to form a hard tissue barrier against microbial invasion. Autophagy participates in odontogenic differentiation during inflammation in vitro, but its role in pulp repair remains unclear. This study investigated how autophagy regulated odontogenic differentiation within the inflammatory microenvironment, emphasising the regulatory role of connexin43 (Cx43) on autophagy.</p> <h2>Methodology</h2> <p>Autophagy activation was detected in inflamed pulpal tissues using immunofluorescence (IF). Human dental pulp cells (hDPCs) were stimulated with 0.1/5 μg/mL lipopolysaccharide (LPS). Autophagy dynamics, including autophagic flux, were analysed through western blotting (WB), transmission electron microscopy (TEM), and mRFP-GFP-LC3 plasmid transfection. Odontogenic differentiation and mineralisation were assessed using molecular assays and Alizarin Red staining. Pharmacological inhibitors or activators were applied to determine autophagy's role. Cx43 knockdown in hDPCs and a dentine injury model in Cx43 cKO mice were used to validate their effects on autophagy. Results were analysed by two-way ANOVA.</p> <h2>Results</h2> <p>Autophagy-related proteins were predominantly localised in the odontoblast layer. As dental pulp infection advanced, concurrent upregulation of LC3 and p62 levels was observed, indicating that autophagy activation occurs in the pulp alongside potential impairment of autophagic flux. 0.1 μg/mL LPS promoted autophagic flux, thereby facilitating odontogenic differentiation and mineralisation, whereas autophagy inhibition attenuated these effects. Conversely, 5 μg/mL LPS induced autophagosome accumulation but blocked autophagic flux, suppressing odontogenic differentiation and mineralisation; however, restoring autophagic flux reversed this inhibition. These data suggested that maintenance of autophagic flux integrity is essential for sustaining odontogenic differentiation capacity under inflammatory stress. Cx43 knockdown under high-inflammatory conditions rescued autophagic flux and improved differentiation. Similarly, in the dentine injury model of cKO mice, Cx43 deletion attenuated p62 expression while upregulating DSPP expression, accompanied by enhanced tertiary dentine formation beneath the injury site, indicating that blockade of Cx43 promotes autophagic flux to improve pulp repair.</p> <h2>Conclusion</h2> <p>Autophagy regulates both inflammatory responses and repair processes in dental pulp. Specifically, maintaining functional autophagic flux ensures cells adapt to pathological stress while retaining their ability to form mineralised tissue. Cx43 inhibition promotes pulp repair through restoration of autophagic flux under inflammatory conditions, highlighting its potential as a therapeutic target for deep caries by synergistically modulating inflammation and promoting regeneration.</p> Unveiling the Vital Role of Dental Nerves in Dental Pulp Immune Defence and Repair https://onlinelibrary.wiley.com/doi/10.1111/iej.70040?af=R International Endodontic Journal urn:uuid:6de0a990-aed1-07d1-f9a6-219e09831f23 Sat, 04 Oct 2025 00:11:29 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Background</h2> <p>Dental pulp sustains oral health through dentine formation, sensation, nutrition and defence. Beyond these classical roles, pulpal nerves have emerged as key coordinators of immune responses and tissue repair. While traditionally viewed as limited to sensory and vascular regulation, recent advances reveal that the nervous system interacts with immune mechanisms to manage inflammation and facilitate regeneration following injury or infection.</p> <h2>Objectives</h2> <p>To synthesise evidence on the anatomy, distribution and functional diversity of dental pulp innervation, emphasising how nerves regulate innate/adaptive immunity and orchestrate pulp tissue repair and regeneration.</p> <h2>Method</h2> <p>The review included studies up to the search period, utilising PubMed and Google Scholar. Search terms covered nervous-system concepts (“nerves”, “neuropeptides”, “nervefibres”, “Schwann cells”) and immune/repair concepts (“immune response”, “inflammation”, “immune cells”, “fibroblasts”, “odontoblasts”, “dental pulpstem cells”, “dentine regeneration”, “odontogenic differentiation”). Key termswere combined with Boolean operators: [nervous-system terms] AND [immune/repairterms] AND [dental], to capture studies on the role of dental nerves in pulpimmune defence and repair.</p> <h2>Results</h2> <p>In innate immunity, dental nerves recognise pathogens, undergo sprouting in inflamed pulp, mediate neurogenic inflammation and engage in dynamic crosstalk with immune cells. In adaptive immunity, they influence antigen presentation and regulate T-cell activation through neuropeptides, highlighting their central role in immune modulation. Furthermore, dental nerves are indispensable for tissue repair, facilitating key processes such as progenitor cell recruitment, proliferation, differentiation and reparative dentine formation. Schwann cells and sensory and sympathetic innervation play distinct yet interconnected roles throughout these stages.</p> <h2>Conclusion</h2> <p>The neuro-immune-endodontic axis is central to the pulp's ability to defend and repair itself, offering insights into innovative therapeutic strategies for managing dental pulp diseases. By integrating neural regulation into endodontic therapies, we can develop more effective treatments that leverage the complex interplay between the nervous and immune systems, enhancing outcomes for dental health and regeneration.</p> Uncertainty in Relation to Clinical Experience—A Qualitative Study on Dental Students' Reflections on Risk Assessment of Root Filled Teeth https://onlinelibrary.wiley.com/doi/10.1111/iej.70047?af=R International Endodontic Journal urn:uuid:d7b3ce68-300d-de51-fee6-c869f9cda584 Thu, 02 Oct 2025 10:33:31 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>In uncertain clinical situations, such as assessing the risk of exacerbation of apical periodontitis in root-filled teeth, undergraduate students can benefit from being trained to reflect. This study aimed to explore how students specifically reflected on clinical experiences in relation to uncertainty when assessing a case involving a root-filled tooth with apical periodontitis.</p> <h2>Methodology</h2> <p>Short reflections were written by 52 dental students at Malmö University in 2021. All students were asked to reflect on the risk for exacerbation of apical periodontitis in a case with a root-filled tooth with a diffuse widening of the periodontal ligament space. The reflections were written according to prompts developed to stimulate reflection. For each student, the reflections were analysed by a qualitative method, Systematic Text Condensation (STC).</p> <h2>Results</h2> <p>The analysis of the qualitative data resulted in the formulation of two themes about experience and lack of experience: Theme 1 ‘The meaning of clinical experience’ and Theme 2 ‘Differences and similarities’. The themes were subdivided into nine subgroups and described the relationship between experience and certainty.</p> <h2>Conclusions</h2> <p>The students believed that certainty comes with experience even when there is a lack of scientific evidence.</p> Comparative Analysis of AI‐Generated and Manually Designed Approaches in Accuracy and Design Time for Surgical Path Planning of Dynamic Navigation‐Aided Endodontic Microsurgery: A Retrospective Study https://onlinelibrary.wiley.com/doi/10.1111/iej.70045?af=R International Endodontic Journal urn:uuid:b9cd52b2-9d22-9829-d4d1-43e8a9db35e2 Wed, 01 Oct 2025 11:59:48 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To compare the accuracy and design time of artificial intelligence (AI)-generated and manually designed (MD) surgical pathways for osteotomies and root-end resections in dynamic navigation (DN)-aided endodontic microsurgery (EMS).</p> <h2>Methodology</h2> <p>Fifty-one surgical pathways were analysed, each planned using both AI and MD methodologies. Accuracy was assessed using the DCARE Navigation System (v3.2, MedNav Ltd) and AutoCAD (2023, Autodesk Inc.), evaluating five parameters: start deviation, end deviation, angular deviation, root-end resection length deviation, and root-end resection angulation deviation. Design time was measured from the point of CBCT dataset import to the finalisation of the surgical pathway design. Mann–Whitney <i>U</i> test was used to compare the accuracy and design time of the AI and MD groups, whereas the rank-based ANCOVA was used to assess deviations according to tooth type, jaw type, and root number. Statistical significance was set at <i>p</i> &lt; 0.05.</p> <h2>Results</h2> <p>Compared with the MD group, the AI group exhibited significantly smaller root-end resection length deviations (AI: 0.01 [0.01, 0.02] mm; MD: 0.02 [0.01, 0.03] mm; <i>p</i> = 0.029) but significantly larger root-end resection angulation deviations (AI: 3.48 [1.01, 7.48]; MD: 0.35 [0.16, 0.73]; <i>p</i> &lt; 0.001). There were no significant differences in the start deviation, end deviation, angular deviation, root-end resection length deviation, or root-end resection angulation deviation across tooth type, jaw type, or root number. The design time was significantly shorter in the AI group than in the MD group (55 [21, 74] s vs. 379 [215, 553] s; <i>p</i> &lt; 0.001).</p> <h2>Conclusions</h2> <p>A clinically operational AI-based surgical path design approach is capable of minimising manual interventions and delivering time-efficient, accurate results for clinical use. The integration of AI with DN-aided EMS may contribute to the development of increasingly autonomous surgical procedures.</p> Prevalence, Classification and Factors Associated With Cemental Tears—A Retrospective Observational Cross‐Sectional Study in a Postgraduate Endodontic Clinic https://onlinelibrary.wiley.com/doi/10.1111/iej.70042?af=R International Endodontic Journal urn:uuid:0643bfe8-1920-af9f-12b2-889ac5de6d46 Tue, 30 Sep 2025 08:53:19 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Introduction</h2> <p>There is a lack of epidemiology studies on cemental tears. This study aimed to (i) investigate the prevalence of cemental tears among the patients referred to a Postgraduate Endodontic Clinic, (ii) classify the cases diagnosed with cemental tears, and (iii) assess factors associated with cemental tears.</p> <h2>Materials and Methods</h2> <p>This retrospective, cross-sectional study included 445 cases/teeth recruited between 1 September 2019 and 31 March 2024 at a University Postgraduate Endodontic Clinic. Information was collated from the clinical records of case history, clinical findings and radiographic interpretations from periapical radiograph (PR) and cone beam computed tomography (CBCT) images. For each case/tooth, cemental tear/s were categorised as either absent or present, and those with cemental tear/s were further classified. Thirty potential factors were studied, including patient-, jaw-, tooth-, previous endodontic treatment and periodontal-related factors. Factors were individually tested using univariate analysis with Pearson chi-squared (exact) tests. Any significant factors identified were further subjected to multiple logistic regression analyses based on a forward stepwise regression model (<i>p</i> &lt; 0.05).</p> <h2>Results</h2> <p>Cemental tear/s were found in 25 out of 445 cases/teeth, with a prevalence of 5.6%. Sensitivity and specificity of PR in detecting cemental tears were 0.6 and 1.0, respectively. Most cases/teeth detected were classified as Class 2 and 4 (<i>n</i> = 19, 76%) or Stage C and D (<i>n</i> = 19, 76%). Mean age of the subjects with cemental tears was 58.7 years, with comparable prevalence between males and females. Most cases (72%) with cemental tear/s had root canal treatment initiated or completed. Incisors, increased tooth mobility, severe crestal bone loss and adequate root filling quality were significantly associated with the higher prevalence of cemental tears (<i>p</i> &lt; 0.05).</p> <h2>Conclusion</h2> <p>Cemental tears should always be considered as a differential diagnosis in endodontic practice. Clinicians should be particularly vigilant for increased risks of cemental tears in incisors, mobile teeth, teeth exhibiting increased crestal bone loss and those with adequately filled root canals, as they may be misdiagnosed as periodontal-endodontic lesions. The use of CBCT is crucial for accurate diagnosis, guiding effective treatment planning and improving clinical outcomes in endodontic management.</p> Outcome of Partial Pulpotomy in Mature Permanent Molars After Lavage With Chlorhexidine or Sodium Hypochlorite: A Randomised Clinical Trial https://onlinelibrary.wiley.com/doi/10.1111/iej.70043?af=R International Endodontic Journal urn:uuid:3e3cd01d-7036-94cf-2bf5-e1583262128a Tue, 30 Sep 2025 08:05:09 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This randomised clinical trial compared the effect of wound lavage using chlorhexidine (CHX) versus sodium hypochlorite (NaOCl) on the outcome of partial pulpotomy (PP) in mature permanent molars with carious pulpal exposure and symptomatic irreversible pulpitis (SIP).</p> <h2>Methodology</h2> <p>In this double-arm parallel-group randomised clinical trial, 104 mandibular molars undergoing PP were randomised equally to either NaOCl lavage group (NL) (<i>n</i> = 52) or CHX lavage group (CL) (<i>n</i> = 52). The pulpal wound after pulp amputation during PP was irrigated with 3% NaOCl in the NL and 2% CHX in the CL group. After haemostasis, ProRoot Mineral Trioxide Aggregate (ProRoot MTA) was used as a pulpotomy agent. Patients were evaluated for pain experience at every 24 h for 7 days, clinical success at 3, 6 and 12 months, and radiographic success at 6 and 12 months. Data were analysed using Mann–Whitney <i>U</i> test to compare age, duration of haemostasis, pain score and analgesic consumption between groups and Chi-square test/Fisher's exact test to compare gender, the number of tooth surfaces involved by caries, hard tissue barrier, clinical and radiographic success, pain incidence and pulp sensibility responses.</p> <h2>Results</h2> <p>Ninety-nine patients were assessed for clinical and radiographic success at 12 months follow-up. The NL group showed a higher success (91.8%) than the CL group (84%), albeit with no significant difference (<i>p</i> &gt; 0.05). No significant difference was observed between the groups in postoperative pain experience (<i>p</i> &gt; 0.05). Significantly less time was required to achieve haemostasis in NL (<i>p</i> &lt; 0.001), and evidence of hard tissue barrier formation was significantly higher in the CL group (<i>p</i> = 0.024).</p> <h2>Conclusion</h2> <p>Comparable success was observed following the use of the two lavage agents during PP in managing cariously exposed adult teeth with SIP. CHX can serve as a suitable alternative to NaOCl as a pulpal wound lavage agent.</p> <h2>Trial Registration</h2> <p><a target="_blank" title="Link to external resource" href="http://clinicaltrials.gov">clinicaltrials.gov</a> identifier: NCT06240130</p> Outcome of High‐Fidelity 3D Jaw Model Simulations in Enhancing Endodontic Microsurgical Training https://onlinelibrary.wiley.com/doi/10.1111/iej.70041?af=R International Endodontic Journal urn:uuid:7b5bce7d-f3af-3f28-584c-1276b5e44822 Fri, 26 Sep 2025 05:34:45 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Background</h2> <p>Endodontic microsurgery (EMS), indicated to manage teeth unresponsive to conventional root canal treatment, requires advanced technical expertise and clinical judgement. Traditional pre-clinical training methods lack fidelity and fail to replicate diseased states, leading to a steep learning curve clinically. High-fidelity 3D jaw model simulations offer a realistic and repeatable training solution, bridging the gap between theory and clinical practice.</p> <h2>Aim</h2> <p>To evaluate the effectiveness of high-fidelity 3D jaw model simulations in enhancing residents' confidence and preparedness for endodontic microsurgery.</p> <h2>Methodology</h2> <p>A descriptive cross-sectional study was conducted involving second-year Endodontic residents enrolled in a postgraduate programme at the National University of Singapore. The intervention group (<i>n</i> = 11; 2021–2023 cohorts) participated in a structured four-session simulation training using high-fidelity 3D jaw models replicating anatomical details and periapical pathology. The curriculum incorporated diverse clinical scenarios, deliberate practice, and structured feedback. The control group (<i>n</i> = 4; 2020 cohort) attended a single-session workshop using pig mandibles. Pre- and post-workshop questionnaires were administered to assess self-reported confidence and preparedness using questions adapted from the Simulation Design Scale (SDS) and the Student Satisfaction and Self-Confidence in Learning (SSSCL) scale. Residents also completed a post-surgical evaluation after their first EMS procedure.</p> <h2>Results</h2> <p>Residents trained with 3D models demonstrated greater improvements across all domains. Confidence in treatment planning improved from 2.45 ± 0.93 to 3.68 ± 0.69, compared to 3.75 ± 0.50 to 4.00 ± 0.00 in controls. Preparedness for EMS increased from 1.54 ± 0.82 to 3.20 ± 0.91 in the 3D group, and from 2.00 ± 0.82 to 2.75 ± 0.96 in the control group. Confidence in independently performing EMS rose from 1.27 ± 0.47 to 3.03 ± 0.95 in the 3D group, compared to 2.25 ± 0.82 to 3.00 ± 0.82 in the control group. The 3D group reported higher ratings for simulation realism, reduced stress, and greater perceived preparedness for clinical EMS.</p> <h2>Conclusion</h2> <p>High-fidelity 3D jaw model simulations were effective in improving residents' confidence and preparedness for EMS. These findings support the integration of 3D simulation into Endodontic training to enhance clinical readiness and surgical competence.</p> Biological Advantages of Calcium Hypochlorite Solution Over Sodium Hypochlorite for Regenerative Endodontic Procedures: An Ex Vivo and In Vitro Study on Human Apical Papilla https://onlinelibrary.wiley.com/doi/10.1111/iej.70038?af=R International Endodontic Journal urn:uuid:85bbb7ed-65c7-cc81-9e4a-c86856bf0b44 Thu, 25 Sep 2025 10:59:31 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>Calcium hypochlorite [Ca(OCl)<sub>2</sub>] has been proposed as an alternative to sodium hypochlorite (NaOCl) for use as an irrigant. This study aimed to assess morphological changes in human apical papilla (AP) ex vivo, and to evaluate viability, proliferation, chemotaxis and osteogenic differentiation of human apical papilla cells (hAPCs) in vitro following exposure to Ca(OCl)<sub>2</sub>, in comparison to NaOCl.</p> <h2>Methodology</h2> <p>Ex vivo, three AP samples per group were exposed to 1.5% Ca(OCl)<sub>2</sub>, 1.5% NaOCl or control solutions [17% ethylenediaminetetraacetic acid (EDTA) and saline] for 3 min. The AP sections were stained with haematoxylin and eosin (H&amp;E), Masson's trichrome and Alcian Blue for morphological analysis. In vitro, hAPCs were exposed to Ca(OCl)<sub>2</sub>, NaOCl, EDTA or culture medium. Cell viability was assessed with the methyl-thiazole-tetrazolium (MTT) assay; proliferation by bromodeoxyuridine incorporation; chemotaxis by transwell assay; and mineralised nodule formation by alizarin red staining. Data were analysed by two-way ANOVA followed by Tukey's test or by the Kruskal–Wallis and Dunn tests (α = 0.05).</p> <h2>Results</h2> <p>Ex vivo, marked loss of both cells and extracellular matrix components was observed in the outer layer of AP samples, particularly in the NaOCl and Ca(OCl)<sub>2</sub> groups, with more severe damage found in the NaOCl samples. Samples treated with EDTA exhibited structural organisation similar to those treated with saline. In vitro, Ca(OCl)<sub>2</sub> induced less cytotoxicity, resulted in the highest proliferation (<i>p</i> &lt; 0.05), but promoted lower chemotaxis than the other irrigants (<i>p</i> &lt; 0.05). EDTA and Ca(OCl)<sub>2</sub> led to greater mineralised nodule formation than the other solutions (<i>p</i> &lt; 0.05).</p> <h2>Conclusions</h2> <p>Ca(OCl)<sub>2</sub> at 1.5% caused less structural damage to AP than NaOCl at the same concentration and had a more favourable influence on the viability, proliferation and osteogenic differentiation of hAPCs. Moreover, it did not impair cell chemotaxis. These findings suggest that Ca(OCl)<sub>2</sub> may offer biological advantages in regenerative endodontic procedures.</p> Fibroblast Dysregulation in Multiple Idiopathic External Cervical Resorption: Laboratory Investigation From a Rare Case of 13 Affected Teeth https://onlinelibrary.wiley.com/doi/10.1111/iej.70037?af=R International Endodontic Journal urn:uuid:1fb62602-69ce-d82f-72f2-9d3930dac436 Tue, 23 Sep 2025 09:40:46 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Introduction</h2> <p>Multiple idiopathic external cervical resorption (MIECR) is a rare and aggressive form of external resorption with an unclear aetiology. This study reports and investigates a unique case of extensive MIECR, potentially associated with chemotherapy exposure. The patient, a pharmacist responsible for preparing chemotherapy drugs, developed external cervical resorption affecting 13 teeth, with rapid progression occurring within just one year after starting her occupation. Notably, following local surgical treatment and cessation of high-risk work, the progression of MIECR was temporarily controlled.</p> <h2>Methods</h2> <p>Whole-exome sequencing was conducted to identify potential genetic contributors. Granulation tissue removed from the tooth cavity, along with extracted teeth obtained during surgery, was collected for histopathological analysis to characterise the pathological features of MIECR. Single-cell RNA sequencing was performed on granulation tissue and healthy gingival tissue to explore the molecular basis of MIECR. Fibroblast-like cells were isolated from granulation tissue and subjected to in vitro experiments to validate their role in MIECR pathogenesis. Statistical analyses were conducted using Student's <i>t</i>-test or one-way analysis of variance (ANOVA), with a <i>p</i>-value of less than 0.05 considered statistically significant.</p> <h2>Results</h2> <p>Whole-exome sequencing suggested a pivotal role for a <i>GNAS</i> missense mutation in disease pathogenesis. Histopathological analysis revealed extensive fibroblast proliferation and invasiveness within the lesion tissue. Moreover, single-cell RNA sequencing and in vitro experiments demonstrated abnormal fibroblast activity characterised by excessive proliferation and osteoclastic traits, implicating fibroblasts in MIECR progression. Importantly, the inhibition of the PI3K/Akt signalling pathway significantly reduced fibroblast invasion and osteoclastogenesis.</p> <h2>Conclusions</h2> <p>This study offers novel insights into the pathogenesis of MIECR, paving the way for more effective diagnostic and therapeutic strategies.</p> Long‐Term Biobanked Dental Pulp Stem Cells Retain Angiogenic Potential for Vascularised Tissue Engineering—Laboratory Investigation https://onlinelibrary.wiley.com/doi/10.1111/iej.70036?af=R International Endodontic Journal urn:uuid:77e5d63f-07b5-3b4d-ca38-7d88719aea5d Tue, 23 Sep 2025 00:00:00 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This study aimed to evaluate whether human dental pulp stem cells (DPSCs), after long-term biobanking (7–8 years), retain their pro-angiogenic properties and can be used to engineer vascularised tissues, addressing their potential for clinical translation in regenerative dentistry.</p> <h2>Methodology</h2> <p>Cryopreserved DPSCs from adolescent donors were recovered from biobanking and characterised for chromosomal integrity, MSC immunophenotype and multipotency. After conditioning in pro-angiogenic conditions in vitro, gene and protein expression were analysed by RT-qPCR array, flow cytometry and high-throughput immunophenotyping. Functional angiogenic capacity was assessed via in vitro tube formation, <i>ex ovo</i> CAM implantation assay, organ-on-chip perfusion model and long-term culture (45 days) in clinical-grade GelMA hydrogels, with and without HUVECs.</p> <h2>Results</h2> <p>Biobanked DPSCs retained MSC identity and multi-lineage differentiation potential. Pro-angiogenic/endothelial conditioning enhanced the expression of angiogenic/endothelial genes (PECAM1, VEGFR2, NRP1, ACE), yet most cells maintained a pericyte-like phenotype. Both naive and endothelial-conditioned DPSCs (i.e., naiveDPSCs and endoDPSCs, respectively) significantly enhanced vascular ingrowth in the CAM model. In the organ-on-chip system, naiveDPSCs formed perfusable vasculature with HUVECs and differentiated into perivascular cell types. Most notably, endoDPSCs alone successfully generated vascularised tissue with both CD31(+) and αSMA(+) cells present in GelMA hydrogels after prolonged stimulation.</p> <h2>Conclusion</h2> <p>Long-term biobanked DPSCs preserve their angiogenic potential and, following extended endothelial induction, can independently generate vascularised tissue in 3D in vitro culture models. This is the first report demonstrating the comprehensive pro-angiogenic characterisation and the feasibility of using biobanked DPSCs for vascularised tissue engineering, highlighting their strong clinical applicability for future regenerative therapies.</p> A Protocol for the Development of a New Three‐Dimensional Classification of Dens Invaginatus Using Cone Beam Computed Tomography Imaging https://onlinelibrary.wiley.com/doi/10.1111/iej.70035?af=R International Endodontic Journal urn:uuid:05732a03-90ab-18fb-5f10-49bfd6f8fb04 Thu, 18 Sep 2025 09:05:48 -0700 International Endodontic Journal, EarlyView. Modelling of the Systemic Inflammatory Host Response in Relation to the Microbiome of the Endodontic Infection https://onlinelibrary.wiley.com/doi/10.1111/iej.70023?af=R International Endodontic Journal urn:uuid:a093744a-b36f-ab56-0870-8dc68fb6cf13 Thu, 18 Sep 2025 08:59:21 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This study aimed to investigate systemic inflammatory responses in individuals with apical periodontitis (AP) compared to age-matched healthy controls, using advanced multiway modelling techniques. We examined associations between inflammatory mediators, age, gender, symptomatic status, and the microbial composition and function to better understand host–microbe interactions in AP.</p> <h2>Methods</h2> <p>We conducted a longitudinal study with 53 participants (27 with AP, 26 controls) aged 18 to 80. Blood inflammatory mediators were measured at multiple time points. Root canal microbiome and potential functions were analysed using 16S rRNA gene sequencing. Data were analysed using Parallel Factor Analysis (PARAFAC) and Advanced Coupled Matrix and Tensor Factorization (ACMTF) to capture time-resolved variation.</p> <h2>Results</h2> <p>PARAFAC revealed that IL-4 levels were significantly elevated in AP cases, suggesting a role for adaptive immune activation. Age strongly influenced markers such as CRP, TNF-α, and VEGF. Symptomatic AP cases showed higher CRP and lower OPG levels, indicating more active inflammation and altered bone metabolism. ACMTF identified associations between specific taxa (e.g., <i>Parvimonas micra</i>, <i>Streptococcus mutans</i>) and inflammatory mediators, with functional analysis highlighting enriched pathways like sphingolipid signalling in asymptomatic cases.</p> <h2>Conclusion</h2> <p>This study provides novel insights into the systemic immune profile of individuals with AP. IL-4 and bone metabolism markers may serve as potential biomarkers for distinguishing AP status. Our findings support the relevance of systemic inflammation in endodontic infections and underscore the value of multi-marker, multivariate approaches to better characterise disease progression and host–microbiome interactions. Such insights could contribute to improved risk stratification and personalised management in dental and systemic health contexts.</p> Yerba Mate (Ilex paraguariensis A. St.‐Hil.) Reduces Oxidative Stress and Bone Resorption in Apical Periodontitis https://onlinelibrary.wiley.com/doi/10.1111/iej.70031?af=R International Endodontic Journal urn:uuid:292e308b-e312-7b08-7b75-330c8d164251 Tue, 16 Sep 2025 03:02:40 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>Apical periodontitis (AP) is a highly prevalent chronic inflammatory disease that can exert systemic effects by releasing biochemical mediators that initiate and regulate the immune response. Yerba Mate (<i>Ilex paraguariensis</i>, YM), a popular plant broadly consumed in South America, is rich in biologically active compounds known for their therapeutic potential. This study assessed Y's in vitro cytocompatibility, anti-osteoclastogenic and immunomodulatory effects on oral stem cells and macrophages, as well as its in vivo potential to reduce AP severity and systemic side effects.</p> <h2>Methodology</h2> <p>In vitro, instant powdered YM was dissolved in distilled water, filtered and diluted in culture media to final concentrations ranging from 1 to 200 μg/mL. Cell viability and pro-inflammatory cytokine release (IL-1α, IL-6, TNF-α) were assessed in human exfoliated deciduous teeth stem cells. The NF-κB pathway and anti-osteoclastogenic activity were evaluated using a luciferase reporter assay and TRAP staining in RAW 264.7. Forty male Wistar rats were divided into control (C), YM-treated(YM), AP-induced (AP) and AP with YM treatment (AP + YM). YM treatment (20 Mg/Kg/Day) was administered via gavage for 58 days. AP was induced after 28 days of YM intake, and the animals were euthanised 30 days later. In serum, systemic redox state was assessed via total antioxidant capacity (TAC) and thiobarbituric acid reactive substances (TBARS). Histological and immunohistochemical analyses evaluated inflammation, cytokine expression (TNF-α, IL-6, IL-10 and IL-17) and bone resorption markers. Micro-CT quantified alveolar bone loss. Data were analysed at <i>p</i> &lt; 0.05.</p> <h2>Results</h2> <p>YM treatment demonstrated significant anti-inflammatory, antioxidant and bone-protective effects. In vitro, YM-supported cell viability, reduced TNF-α and IL-1α, inhibited NF-κB activation and suppressed osteoclastogenesis. In vivo, YM treatment restored systemic antioxidant capacity and reduced lipid peroxidation, mitigating AP-induced oxidative stress. Furthermore, YM intake attenuated the local inflammatory response and reduced the bone resorptive activity associated with AP.</p> <h2>Conclusion</h2> <p>In vitro, YM suppressed pro-inflammatory cytokines and NF-κB, inhibited osteoclastogenesis and was cytocompatible. In vivo, it reversed AP-induced redox state and reduced inflammation and bone resorption, suggesting therapeutic promise.</p> Enhancing the Quality of Single Cone Obturation Using Hydroxyapatite Precursor Grafted Nanocomplex for Dentine Conditioning: An In Vitro Study https://onlinelibrary.wiley.com/doi/10.1111/iej.70034?af=R International Endodontic Journal urn:uuid:9409b426-9daa-959c-454e-05d41cd9c0f9 Fri, 12 Sep 2025 04:44:43 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This study aimed to quantify the effect of chitosan-hydroxyapatite precursor nanocomplexes (C-HA) on void reduction in the root canal system and isthmus regions, characterise void distribution patterns and assess sealer-dentin interface adaptation post-conditioning.</p> <h2>Methodology</h2> <p>Vertucci type II and Yin type IV mesial root canals from 24 extracted mandibular first molars were randomly divided into two groups (<i>n</i> = 12): (1) C-HA conditioned and (2) control (deionised water). All canals underwent standardised preparation using ProTaper Next files with 3% NaOCl irrigation (2 mL per file change) and final irrigation with 17% EDTA (5 mL, sonic activation) followed by 3% NaOCl (5 mL) and a final deionised water rinse (5 mL). Before obturation, the C-HA group received 5 min of C-HA solution (2 mg/mL) treatment with active agitation by ProTaper Next X2 gutta-percha cone, while the control group received equivalent water treatment. Canals were obturated using the single-cone technique with Ceraseal. High-resolution Micro-CT (8.6 μm voxel size) quantified void percentages in the entire canal system and isthmus regions, with analysis stratified by coronal, middle and apical thirds. Selected specimens underwent SEM evaluation of interfacial adaptation. Statistical analysis used the independent samples <i>t</i>-test, two-way ANOVA with Tukey's post hoc tests (<i>α</i> = 0.05), and Fisher's exact test.</p> <h2>Results</h2> <p>No significant differences related to the canal/isthmus pre-treatment volumes and isthmus characteristics were noted between the two groups. Micro-CT analysis revealed significantly lower void percentages in C-HA-treated canals compared to controls (9.21% vs. 19.01% in the entire canal system and 19.07% vs. 55.65% in the isthmus regions, <i>p</i> &lt; 0.001). Analysis of the void distribution patterns further demonstrated statistically significant differences between the groups in the cervical and middle root thirds (<i>p</i> &lt; 0.05). SEM evaluation showed continuous, gap-free interfaces with bioactive mineralization in C-HA-treated canals, contrasting with discontinuous adaptation and sparse precipitates in controls.</p> <h2>Conclusion</h2> <p>C-HA dentine conditioning significantly improved obturation quality with Ceraseal bioceramic sealer by reducing voids in isthmus regions and enhancing sealer-dentin interfacial adaptation.</p> Prevalence and Predisposing Factors of Periapical Osteoperiostitis: A Retrospective Cross‐Sectional Study https://onlinelibrary.wiley.com/doi/10.1111/iej.70033?af=R International Endodontic Journal urn:uuid:4ff6a213-7b2f-5688-9bdd-ba7bc3894247 Fri, 12 Sep 2025 04:42:56 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>Periapical Osteoperiostitis (PO) is an inflammatory reaction of the periosteum located on the maxillary sinus floor, characterised by reactionary deposition of bone caused by periradicular disease of the maxillary posterior teeth. Radiographically, PO presents as a radiopaque ‘halo’ over the involved root(s). There is a gap in the literature regarding the prevalence and predisposing factors of PO. This study aims (1) to evaluate the prevalence of PO in maxillary posterior teeth amongst patients at NYU College of Dentistry, Department of Endodontics, and (2) to identify predisposing factors associated with PO.</p> <h2>Methodology</h2> <p>A chart review and cone-beam computed tomography (CBCT) evaluation were conducted at NYU College of Dentistry from 2016 to 2021. Initially, 586 scans were screened, and 335 scans were included. The presence of PO, mucositis, sinus perforation, age, sex, pulpal and periapical diagnosis, size of the lesion, the vertical and horizontal distance between the sinus floor and roots, number of roots with apical lesions, type of tooth, and iatrogenic errors during treatment were recorded. Data were analysed using chi-square, Fisher's tests and logistic regression.</p> <h2>Results</h2> <p>Of the 335 CBCT scans included, 98 scans (29.3%) presented with PO. The presence of mucositis was associated with 3.37 times higher odds of PO than those without mucositis. Each incremental increase in the size of the lesion (CBCTPAI) was associated with a 2.51 increase in the odds of PO occurrence, and the vertical distance between the sinus and roots was statistically significant (<i>p</i> &lt; 0.001).</p> <h2>Conclusion</h2> <p>The prevalence of PO in this study was higher than previously reported. Three factors were significantly associated with PO: the presence of mucositis, the size of the lesion, and the vertical distance between the sinus and roots.</p> The Relationship Between Pulpal Diagnostic Conditions and Potential Inflammatory Biomarkers https://onlinelibrary.wiley.com/doi/10.1111/iej.70030?af=R International Endodontic Journal urn:uuid:5ec21760-2b1c-b415-6769-1a3be1b83072 Tue, 09 Sep 2025 01:33:43 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Introduction</h2> <p>Accurate diagnosis of pulpal health is crucial to identify the most effective therapeutic approach. However, differentiating pulpal conditions, which may require different treatment approaches, remains a challenge. This study aimed to address this gap by investigating the protein levels of 17 inflammatory biomarkers simultaneously in the dental pulp with different clinical diagnoses.</p> <h2>Methods</h2> <p>This study employed a cross-sectional exploratory design, enrolling 64 adult patients. After obtaining ethical approval, researchers conducted clinical and radiographic examinations to categorise teeth into four diagnostic groups: normal pulp, reversible pulpitis, symptomatic irreversible pulpitis and asymptomatic irreversible pulpitis. Pulpal blood samples were then collected and analysed using Luminex technology to measure the levels of inflammatory proteins and matrix metalloproteinases (MMPs). Statistical analyses, including the Mann–Whitney <i>U</i> test and Spearman's rank correlation, were used to compare the levels of these markers across the different diagnoses and to assess their correlation with patient symptoms.</p> <h2>Results</h2> <p>The study revealed significant increases in several inflammatory proteins, including IL-4, IL-8, MCP-1, MIP-1α, RANTES and MMP-9, in both types of irreversible pulpitis cases compared with other diagnostic categories <i>p</i> &lt; 0.05. These elevated levels exhibited positive correlations with patient-reported pain scores, instances of spontaneous pain and bleeding times. Notably, only IL-4 and IL-7 exhibited correlations with prolonged bleeding times (over 10 min) <i>p</i> &lt; 0.05, while IL-1α and MMP-2 were associated with shorter bleeding times (under 10 min) <i>p</i> &lt; 0.05. Additionally, IL-8 and MCP-1 levels were significantly associated with positive palpation findings <i>p</i> &lt; 0.05, whereas MIP-1α and MMP-1 were correlated with positive percussion results <i>p</i> &lt; 0.05.</p> <h2>Conclusion</h2> <p>Differential specific inflammatory potential biomarker levels may differentiate pulpal disease states. Integrating molecular diagnostics into longitudinal clinical trials and eventually into routine endodontic practice, could revolutionise treatment decisions.</p> Modulation of Prickle2 Expression to Facilitate Dentine Formation: A Laboratory Investigation https://onlinelibrary.wiley.com/doi/10.1111/iej.70024?af=R International Endodontic Journal urn:uuid:ebbc14b2-5bfc-0bc9-46b9-791f02248205 Sun, 07 Sep 2025 10:49:31 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>Prickle planar cell polarity (PCP) protein 2 (Prickle2) encodes a homologue of <i>Drosophila</i> prickle and is involved in the non-canonical Wnt/PCP signalling pathway. However, its exact role in dentinogenesis remains unclear. Dentinogenesis, a key process in tooth morphogenesis, involves the patterned arrangement of odontoblasts and the formation of dentine matrix along the pulp cavity. This study investigates the role of PCP signalling, particularly Prickle2, in odontogenesis and dentine formation. Additionally, this study evaluates the potential application of Prickle2 modulation for dentine regeneration using an animal experimental model.</p> <h2>Methodology</h2> <p>The developmental function of Prickle2 in tooth morphogenesis was examined by analysing its precise expression pattern in the primary enamel knot. Gain and loss of function studies were performed using in vitro organ cultivation and renal capsule transplantation. At embryonic day 13 (E13), Prickle2 was knocked down using small interfering ribonucleic acid (siRNA) treatment, and histogenesis, cellular physiology (proliferation and apoptosis), and the expression of PCP pathway-related genes and tooth-related signalling molecules were examined. Furthermore, renal capsule transplantation was conducted for 3 weeks to analyse the morphological changes in tooth crown formation. To evaluate the clinical applicability of Prickle2 modulation in dentine regeneration, a pulp exposure animal model was employed, locally administering siRNA against Prickle2 into the exposed pulp cavity of the maxillary first molar at week 8 for 6 weeks.</p> <h2>Results</h2> <p>At E13.5, in situ hybridization revealed the distinctive expression of Prickle2 in the enamel knot area. Knockdown of Prickle2 at E13 led to significant alterations in histogenesis and changes in key signalling molecule expression. Renal capsule transplantation resulted in morphological changes, including a thicker pre-dentine layer and the formation of a more opaque crown. In the pulp exposure model, siRNA treatment facilitated the formation of a dentinal bridge compared to controls.</p> <h2>Conclusion</h2> <p>Our findings suggest that Prickle2 regulates dentinogenesis through Wnt/PCP signalling. Modulating Prickle2 expression presents a promising approach for dentine regeneration.</p> Redefining Root Canal Shaping: From Size to Volume—The Functional Endodontic Volume Concept https://onlinelibrary.wiley.com/doi/10.1111/iej.70029?af=R International Endodontic Journal urn:uuid:79a9724a-fa58-4ff4-1cac-bb8de0a1a835 Thu, 04 Sep 2025 00:00:00 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This article aims to introduce and elaborate on the innovative concept of <i>Functional Endodontic Volume</i> (FEV), a biologically driven approach to root canal shaping. This concept emphasizes the importance of volumetric preparation aimed at enhancing irrigation dynamics during root canal treatment, all while maintaining the tooth's structural integrity.</p> <h2>Summary</h2> <p>In recent years, contemporary endodontics has progressively shifted towards methods that prioritize irrigation-based disinfection. Traditional philosophies surrounding canal preparation have predominantly revolved around standardized apical sizes and tapers, often failing to address the true objectives of modern root canal treatment. This article advocates for the FEV concept—a sophisticated and tailored shaping strategy focused on optimizing the efficacy of irrigants used in treatment, promoting mechanical safety, and conserving the structural framework of the tooth. The FEV approach moves beyond merely considering the diameter or taper of the canal; instead, it emphasizes a comprehensive three-dimensional shaping method that is particularly beneficial in anatomically complex root canal systems. By prioritizing the effective exchange of irrigants and the delivery of energy throughout the entire canal volume, this concept not only enhances disinfection but also minimizes the risk of procedural complications. The implications of adopting the FEV concept extend to the clinical and research realms. It can guide the development and refinement of new shaping protocols, the design of endodontic instruments, and the establishment of standardized reporting metrics in endodontic studies. This holistic approach has the potential to revolutionize the way endodontic procedures are performed and assessed.</p> <h2>Conclusion</h2> <p>The FEV approach redefines the objectives of canal shaping by concentrating on achieving an effective disinfection-driven canal volume rather than adherence to fixed apical dimensions. It supports a minimally invasive technique that ensures optimal irrigant exchange and agitation, thereby enhancing overall treatment outcomes. The FEV concept could serve as a valuable clinical and research framework, enabling practitioners and researchers to evaluate and compare various shaping systems with a focus on volumetric efficacy.</p> Laboratory Investigation of Lipid Metabolic Reprogramming in Pulpitis: The Linolenic Acid–FASN–NR4A1 Axis in Modulating Dental Pulp Inflammation https://onlinelibrary.wiley.com/doi/10.1111/iej.70026?af=R International Endodontic Journal urn:uuid:6a94f064-2d72-76dd-4040-980ebc11084d Wed, 03 Sep 2025 00:46:53 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This study explores how lipid metabolic reprogramming contributes to the pathogenesis of pulpitis and identifies key molecular targets involved in regulating inflammation, with the goal of developing metabolic interventions to preserve dental pulp vitality.</p> <h2>Methodology</h2> <p>Primary human dental pulp cells (HDPCs) were stimulated with lipopolysaccharide (LPS) and subjected to integrated transcriptomic and metabolomic profiling to map inflammation-associated metabolic shifts. Functional validation included linolenic acid (LA) supplementation (alone or combined with a Fatty Acid Synthase (FASN) inhibitor, TVB-2640), Nuclear receptor subfamily 4 group A member 1 (NR4A1) knockdown, cytokine/NF-κB assessment (ELISA, Western blot), and lipid droplet/FASN visualisation (immunofluorescence). FASN expression was confirmed in vivo (rat pulpitis model). Key findings were verified in clinical pulpitis samples (histology, immunofluorescence, targeted fatty acid profiling).</p> <h2>Results</h2> <p>LPS stimulation significantly upregulated FASN expression and induced lipid accumulation in HDPCs and rat pulpitis models (<i>p</i> &lt; 0.001). Transcriptomic analysis revealed marked downregulation of NR4A1, while metabolomic profiling showed depletion of key anti-inflammatory/pro-resolving PUFA precursors, including LA and γ-linolenic acid (GLA). Integrated transcriptomic–metabolomic analysis identified LA as a metabolite with high centrality in the lipid metabolic network, and NR4A1 as a significantly downregulated transcription factor linked to multiple lipid-related pathways. LA supplementation suppressed pro-inflammatory cytokines (IL-1β, TNF-α, phosphorylated NF-κB p65) and restored NR4A1 expression (<i>p</i> &lt; 0.05). Combining LA with the FASN inhibitor TVB-2640 synergistically enhanced NR4A1 restoration and anti-inflammatory effects (<i>p</i> &lt; 0.001). siRNA-mediated NR4A1 knockdown abolished the benefits of LA. In human pulpitis tissues, FASN upregulation, NR4A1 downregulation, and elevated palmitic acid were observed (<i>p</i> &lt; 0.001), along with increased levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).</p> <h2>Conclusions</h2> <p>This study reveals a pathological FASN–LA–NR4A1 regulatory axis linking lipid metabolism to inflammatory amplification in pulpitis. Dual targeting of fatty acid synthesis and lipid depletion—through FASN inhibition and LA supplementation—attenuates inflammation via NR4A1-dependent mechanisms. These findings lay the groundwork for metabolic approaches to modulate inflammation in endodontics.</p> The Cost of Instrument Retrieval on the Root Integrity https://onlinelibrary.wiley.com/doi/10.1111/iej.70027?af=R International Endodontic Journal urn:uuid:0d1d0995-5cb1-c382-4913-fcaa608f6f04 Tue, 02 Sep 2025 10:08:12 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To evaluate dentine loss in mesial canals of mandibular molars following instrument fragment retrieval using two techniques.</p> <h2>Methodology</h2> <p>Ten mesial roots of mandibular molars with Type II configuration were selected and scanned in a micro-computed tomography (CT) device. After canal preparation, a 3-mm fragment of a size 35/0.04 rotary instrument was intentionally fractured in the middle third of each mesial canal. In each tooth, one mesial canal was randomly assigned to either ultrasonic retrieval (<i>n</i> = 10) or the combined ultrasonic/lasso technique (<i>n</i> = 10). Removal time was recorded, and pre- and post-retrieval scans were registered to assess changes in dentine thickness, dentine volume, canal volume and cross-sectional area. Data were analysed using Student's <i>t</i>-test, Mann–Whitney <i>U</i> test, Chi-square and Fisher's Exact tests (<i>α</i> = 0.05).</p> <h2>Results</h2> <p>All fragments were successfully retrieved. Ultrasonic removal was faster than the combined technique (<i>p</i> = 0.023) but resulted in greater dentine thickness reduction (<i>p</i> = 0.029). No significant differences were observed in canal area increase between groups (<i>p</i> = 0.698). After instrument retrieval, canal volume increased by 23.8%, while dentine volume decreased by 2.2%. Both techniques led to significant reductions in thick dentine regions and increases in thinner regions after preparation and retrieval (<i>p</i> &lt; 0.001), with no significant differences between groups (<i>p</i> &gt; 0.05).</p> <h2>Conclusions</h2> <p>Both techniques were effective in retrieving fractured instruments and resulted in similar increases in canal area and volume, as well as comparable proportions of cross-sections exhibiting minimal dentine thickness below 0.5 mm. However, while ultrasonic removal was faster, it caused a greater percentage reduction of dentine thickness compared to the combined ultrasonic/lasso technique.</p> Outcome Following Complete and Partial Pulpotomy in Managing Cariously Exposed Mature Permanent Molars With Symptomatic Irreversible Pulpitis: A 5‐Year Follow‐Up of a Randomised Clinical Trial https://onlinelibrary.wiley.com/doi/10.1111/iej.70028?af=R International Endodontic Journal urn:uuid:7692cadd-8c3a-e700-7192-a31d14137f47 Tue, 02 Sep 2025 09:14:49 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Introduction</h2> <p>Numerous studies have reported favourable outcomes following complete pulpotomy (CP) and partial pulpotomy (PP) in cariously exposed mature permanent teeth with symptomatic irreversible pulpitis (SIP) at 1-year follow-up. However, literature on long-term outcomes is sparse. The European Society of Endodontology and the American Association of Endodontists emphasised the need for long-term evidence before establishing pulpotomy as a definitive treatment. This prospective follow-up study aimed to compare 5-year outcomes of CP and PP performed in such teeth.</p> <h2>Methodology</h2> <p>This prospective study followed participants from a previously published superiority randomised trial on CP and PP for managing cariously exposed mature permanent teeth with SIP. The original trial was registered at <a target="_blank" title="Link to external resource" href="http://clinicaltrials.gov">ClinicalTrials.gov</a> (NCT04397315). Ninety-three participants (CP—49, PP—44) received the allocated intervention. Of these, 88 (CP—45, PP—43) participants who attended the 1-year follow-up were recalled for the 5-year follow-up. The primary outcome was combined clinical and radiographic success. Secondary outcome measures included hard tissue barrier (HTB) formation and pulp canal obliteration (PCO). Cases were analysed for restoration integrity, secondary caries, periodontal status and pulp sensibility responses. The impact of various prognostic factors on 5-year success was analysed. Outcome measures at 5-year were compared with 1-year outcomes. Statistical tests included the Mann–Whitney <i>U</i> test, chi-squared test, Fisher's exact test, McNemar's test, intention-to-treat analysis and binary logistic regression, with significance set at <i>p</i> &lt; 0.05.</p> <h2>Results</h2> <p>At 5 years, 59 of 88 participants (CP—28, PP—31) were available for follow-up. The overall success was 83.05%, with no significant difference between groups (<i>p</i> = 0.494, RR = 1.10, 95% CI = 0.88–1.40). While both groups showed comparable evidence of HTB (<i>p</i> = 0.581, RR = 1.06, 95% CI = 0.91–1.23), PCO was significantly more evident in the CP group (<i>p</i> = 0.003, RR = 0.22, 95% CI = 0.07–0.70). The PP group elicited significantly more sensibility responses to cold test (<i>p</i> = 0.015, RR = 2.35, 95% CI = 1.09–7.43). Secondary caries was a significant prognostic factor influencing overall success at 5 years (<i>p</i> &lt; 0.05). No significant differences in success, HTB, or PCO were observed between the 1 and 5 years outcomes in either group (<i>p</i> &gt; 0.05).</p> <h2>Conclusions</h2> <p>CP and PP demonstrated comparable success at 5 years. PP may be preferred given its conservative approach, reduced risk of PCO, and more reliable pulp sensibility reoptimizing responses. Adequate restorative seal is crucial for long-term success.</p> <h2>Trial Registration</h2> <p><a target="_blank" title="Link to external resource" href="http://clinicaltrials.gov">ClinicalTrials.gov</a> identifier: NCT04397315</p> Pre‐Operative Factors on Prognosis of Regenerative Endodontic Procedures: A Systematic Review and Meta‐Analysis https://onlinelibrary.wiley.com/doi/10.1111/iej.70025?af=R International Endodontic Journal urn:uuid:17991e1a-bc36-96de-1657-283751593cee Sun, 31 Aug 2025 08:56:00 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Background</h2> <p>Although regenerative endodontics has advanced in recent years, the influence of pre-operative factors on treatment outcomes remains poorly understood.</p> <h2>Objective</h2> <p>To evaluate the effect of pre-operative factors—including age, gender, tooth type, aetiology of pulp necrosis, stage of root development, clinical signs/symptoms and periradicular status—on the treatment outcomes of regenerative endodontic procedures (REPs) in immature permanent teeth.</p> <h2>Methods</h2> <p>A literature search was conducted on six electronic databases and grey literature to identify studies investigating the effect of pre-operative factors on REP outcomes. The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk-of-Bias 2 tool for randomised clinical trials (RCTs). Meta-analyses of proportions were conducted to estimate pooled rates for the outcomes ‘clinical and radiographic healing’, ‘root development’ and ‘apical closure’ across different pre-operative factors. Associations between these factors and treatment outcomes were assessed through meta-analyses of effect sizes. The certainty of evidence was evaluated using the GRADE approach.</p> <h2>Results</h2> <p>Twenty studies were included, comprising 13 observational studies and seven RCTs. Most studies presented a moderate to high risk of bias. The pooled success rate for clinical and radiographic healing exceeded 81% across all pre-operative factors. Moreover, root development was achieved in 52%–95% of cases, whereas complete apical closure ranged from 32% to 91%. No significant association was found between pre-operative factors and clinical and radiographic healing. It was found that teeth with pulp necrosis due to trauma presented 3.59 times higher relative risk of root development failure compared to those with necrosis due to anatomic anomaly (RR = 3.59, 95% CI 1.21–10.67, <i>p</i> = 0.02). Incisors presented 1.90 times higher relative risk of root development failure (RR = 1.90, 95% CI: 1.37–2.63, <i>p</i> &lt; 0.01) and 1.98 times higher relative risk of incomplete apical closure (RR = 1.98, 95% CI: 1.34–3.13, <i>p</i> = 0.02) compared to premolars. The presence of an apical lesion increased the relative risk of root development failure by 2.55 times (RR = 2.55, 95% CI: 1.63–4.86, <i>p</i> = 0.01). The certainty of evidence was rated as very low.</p> <h2>Conclusion</h2> <p>Pre-operative factors were not significantly associated with clinical and radiographic healing in REPs. However, trauma-related pulp necrosis, tooth type (incisors) and the presence of apical lesions were associated with an increased risk of root development failure. These findings should be interpreted with caution due to between-study heterogeneity, the moderate to high risk of bias and the very low certainty of the evidence.</p> Patient Satisfaction and Long‐Term Outcomes: A 7‐ to 9‐Year Prospective Cohort Study of Root Canal Treatment in the Swedish Public Dental Service https://onlinelibrary.wiley.com/doi/10.1111/iej.70018?af=R International Endodontic Journal urn:uuid:efc110e2-e707-d37d-6c10-2496d6cf7016 Fri, 29 Aug 2025 04:44:58 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This prospective follow-up study aimed to assess patient satisfaction with root canal treatment (RCT) 7–9 years after initiation in a general dental practice setting.</p> <h2>Method</h2> <p>A study population of 243 patients initiated RCT at 20 public dental clinics in the Västra Götaland Region, Sweden. One to 3 years later, 159 patients (67.4%) responded to an 8-item questionnaire assessing patient satisfaction with RCT and treatment results. The questionnaire was sent out again 7–9 years after treatment initiation. Descriptive and analytical statistics were used to compare respondents and non-respondents, tooth groups and comparison over time.</p> <h2>Results</h2> <p>A total of 156 patients (72.2%) responded to the 7–9 years' questionnaire; 82 women (52.6%) and 74 men (47.4%) with a mean age of 59.3 years (SD = ±15.3). Non-respondents were significantly younger (<i>p</i> &lt; 0.001). The majority of RCTs were reported as completed with a root filling (<i>n</i> = 102, 65.4%), although significantly fewer molars were completed (<i>n</i> = 43, 56.6%; <i>p</i> &lt; 0.001). Sixty-six patients (63.5%) reported no current pain, while most of those reporting pain described it as mild (<i>n</i> = 30, 90.9%). More than half of the root filled incisors were associated with current pain (<i>n</i> = 15, 57.7%; <i>p</i> &lt; 0.009). A total of 111 patients (76.0%) recalled the procedure as painful. Chewing ability received the highest satisfaction rating (mean = 1.3). The majority of patients reported they would choose RCT again (<i>n</i> = 114, 77.0%). Among the 17 who answered ‘No’, 13 had undergone extraction, and 3 reported persistent pain following RCT. Over time, the number of extracted teeth increased (<i>p</i> &lt; 0.001), while current pain intensity decreased and retrospective satisfaction with RCT improved (<i>p</i> &lt; 0.001).</p> <h2>Conclusions</h2> <p>Seven to nine years after the initiation of RCT in this general dental practice setting, patient satisfaction remains high despite one-third of treated teeth being reported as extracted. These findings highlight the importance of incorporating patient-reported outcomes in the evaluation of dental procedures, including endodontic treatments.</p> The “Testing Effect” in Undergraduate Endodontic Education: The Impact of Regular Low Stakes Testing on Learning Outcomes and Student Engagement https://onlinelibrary.wiley.com/doi/10.1111/iej.70022?af=R International Endodontic Journal urn:uuid:67aba23b-a131-997b-a1e1-44884fce6790 Fri, 29 Aug 2025 03:17:16 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This study investigates the impact of regular testing on learning outcomes in undergraduate endodontic education. Specifically, it examines whether students perform better at the end of the course on previously tested material compared to non-tested material and explores the role of students' engagement and perceptions of testing in this effect.</p> <h2>Methodology</h2> <p>A within-participants experimental design was employed with 81 third-year dental students enrolled in a preclinical endodontics course. Students were tested on half of the course lectures (tested material) immediately after each lecture, while the remaining lectures served as a control (non-tested material). Testing was conducted using multiple-choice questions on the Blackboard Learn platform with immediate automated feedback. Final exam scores for tested and non-tested material were compared, and a subset of students (<i>n</i> = 44) completed a questionnaire assessing cognitive engagement, emotional engagement, and perceptions of testing.</p> <h2>Results</h2> <p>Students scored significantly higher on tested material (Mean = 25.284, SD = 4.202) compared to non-tested material (Mean = 21.111, SD = 3.847). The mean difference between the two scores was statistically significant with a very large effect size (<i>F</i> <sub>1,80</sub> = 108.329, <i>p</i> &lt; 0.001, <i>η</i> <sub>p</sub> <sup>2</sup> = 0.575). The difference remained significant with a moderate to large effect size after accounting for the grade in the previous course and sex (<i>F</i> <sub>1,78</sub> = 9.392, <i>p</i> = 0.003, <i>η</i> <sub>p</sub> <sup>2</sup> = 0.107). Emotional engagement was found to moderate the effectiveness of testing, with students reporting higher emotional engagement showing greater gains from the intervention.</p> <h2>Conclusions</h2> <p>The findings demonstrate a robust testing effect in undergraduate endodontic education, supporting the hypothesis that retrieval practice enhances learning outcomes. These results suggest that integrating regular, low-stakes testing into dental curricula can enhance dental students' learning outcomes at the end of the course.</p> Teaching Vital Pulp Treatment for Permanent Teeth to Undergraduate/Pre‐Doctoral Students: A Multinational Survey https://onlinelibrary.wiley.com/doi/10.1111/iej.70020?af=R International Endodontic Journal urn:uuid:12d2301e-ed9e-0724-d87a-26012cf8bd08 Fri, 29 Aug 2025 03:10:48 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To investigate the current status of education in vital pulp treatment (VPT) for the management of permanent teeth in relation to undergraduate/pre-doctoral students at a range of dental schools worldwide.</p> <h2>Methodology</h2> <p>The web-based survey consisted of 28 questions that had been validated and piloted by a range of experienced endodontists. Faculty members who taught endodontics at one dental school in each selected country participated in the survey, which was completed in March 2025. Simple descriptive statistics were used to present the data.</p> <h2>Results</h2> <p>Forty faculty members from various countries completed the survey; the majority of which (82.5%) worked at public universities. All participating dental schools included VPT teaching in their undergraduate/predoctoral curricula. The primary method of teaching VPT in the majority of dental schools was didactic lectures. VPT preclinical exercises were included in only 32.5% of the schools. The vast majority of dental schools did not require students to pass a preclinical or clinical competency examination in relation to VPT prior to graduation. Hydraulic calcium silicate materials were the most commonly used for exposed pulps but not for pulps that were not exposed.</p> <h2>Conclusions</h2> <p>VPT has been integrated into the undergraduate/pre-doctoral curriculum of all dental schools that participated in this survey. However, the majority of dental schools that were surveyed lacked preclinical teaching and competency assessments for VPT in both preclinical and clinical scenarios.</p> Innovative Didactic Learning Formats: Have They Improved Dental Education? A Systematic Review and Meta‐Analysis https://onlinelibrary.wiley.com/doi/10.1111/iej.70006?af=R International Endodontic Journal urn:uuid:97716960-5607-b361-2086-569de1fddbe3 Thu, 28 Aug 2025 05:08:55 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Background</h2> <p>New learning methods require higher professor-to-student ratios, increased faculty preparation time, continuous professional development for educators, and expanded physical spaces within university settings.</p> <h2>Objectives</h2> <p>This systematic review aimed to answer the following PICO question: In dental students (P), what is the effectiveness of innovative formats of learning (I) in comparison with traditional formats (C) in terms of educational outcomes and satisfaction (O)?</p> <h2>Methods</h2> <p>After PROSPERO protocol registration, a literature search was conducted using Web of Science (WoS), Scopus, PubMed and Cochrane Central Register of Controlled Trials. Selection of studies was performed in a three-step process: identification, screening and eligibility. Data was extracted and analysed qualitatively and quantitatively. A random-effects meta-analysis was conducted to provide an estimate of the effect of innovative teaching formats in dental education. Additionally, subgroup analyses were performed to investigate potential differences in effectiveness based on the type of innovative teaching intervention.</p> <h2>Results</h2> <p>One hundred and nineteen studies matched the inclusion criteria and were included in the systematic review. A meta-analysis of 23 studies (1074 students in the control and 1021 in the experimental group) revealed significant differences in favour of innovative teaching methods (<i>p</i> &lt; 0.00001) with considerable heterogeneity (<i>χ</i> <sup>2</sup> = 297.46, <i>p</i> &lt; 0.00001; <i>I</i> <sup>2</sup> = 93%). Subgroup analysis also revealed significantly different results depending on the innovative teaching approach (<i>p</i> = 0.02). Both asynchronous independent learning and synchronous learning, either in a large group with the whole class of students using blended learning or in small groups, resulted in a significantly better outcome than traditional learning (overall effect: <i>Z</i> = 5.85; <i>p</i> &lt; 0.00001); however, synchronous blended learning showed a significantly better outcome than the rest of the subgroups (mean difference = 16.59; 95% CI = 9.03–24.15). The quality of the studies varied, with some facing methodological challenges such as inconsistent outcome measurement, which can impact the generalisability of the findings.</p> <h2>Conclusions</h2> <p>Innovative strategies lead to superior knowledge acquisition in comparison with traditional methods. Subgroup analyses favoured synchronous blended learning, but both asynchronous independent learning and synchronous learning formats, whether implemented in large-group settings via blended approaches or in small-group environments, are more effective than traditional instruction.</p> <h2>Trial Registration</h2> <p>PROSPERO (CRD42024569691)</p> Impact of Haptic Simulators and 3D‐Printed Teeth on Dental Students' Self‐Assessment of Endodontic Access Cavities: A Comparative Pilot Study https://onlinelibrary.wiley.com/doi/10.1111/iej.70021?af=R International Endodontic Journal urn:uuid:cb26ae99-83a1-c413-689d-04e75e69dfc2 Wed, 27 Aug 2025 07:39:27 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This study aimed to compare the impact of two innovative training methods, haptic simulators and 3D-printed teeth, on the self-assessment accuracy of dental students when evaluating endodontic access cavities.</p> <h2>Methodology</h2> <p>A prospective, experimental, and comparative educational trial was conducted with undergraduate dental students randomly assigned to two groups: Group S (haptic simulators, <i>n</i> = 12) and Group 3D (3D-printed teeth, <i>n</i> = 10). Participants performed six access cavity preparations over two training sessions and self-assessed their work using a standardised evaluation form. A pre-test and post-test assessment of pre-prepared access cavities was conducted to measure changes in self-assessment accuracy. Evaluations were also performed by experts to establish a gold standard. The percentage of agreement and Cohen's kappa coefficient with 95% confidence intervals (CI) were calculated for both groups. Statistical analyses included McNemar's test, Wilcoxon signed-rank test, and Mann–Whitney <i>U</i> test (<i>p</i> &lt; 0.05).</p> <h2>Results</h2> <p>Both groups improved their self-assessment scores over time. However, only Group S showed a statistically significant increase in correct responses in the post-test evaluation (<i>p</i> = 0.009). The overall agreement between participants and experts remained low in both groups, with Cohen's kappa values indicating fair agreement. The primary source of disagreement was overestimation, particularly in Group 3D. While Group S exhibited better alignment with expert assessments over time, differences between the two groups were not statistically significant.</p> <h2>Conclusions</h2> <p>Haptic simulators and 3D-printed teeth both contributed to students' self-assessment skills. However, haptic simulators were more effective in improving self-assessment accuracy. Despite these improvements, agreement with expert evaluations remained low; highlighting the need for additional feedback and guidance during training.</p> Factors Affecting Root Canal Treatment Case Difficulty, Practitioner Rating of Difficulty and Treatment Complications Among General Dentists and Endodontists: A Prospective Cohort Study From National Dental Practice‐Based Research Network PREDICT Project https://onlinelibrary.wiley.com/doi/10.1111/iej.70019?af=R International Endodontic Journal urn:uuid:3827d693-d3a9-e35d-a9f4-c516c93fc49d Fri, 22 Aug 2025 11:34:57 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>Successful root canal treatment (RCT) is necessary for managing pulpal and periapical disease. The technical quality of RCT affects its outcome. Recognising complicating factors can be important to optimising outcomes. The aims of this study were to compare the practitioner reported case difficulty before and after completion of RCT; and to determine whether any case difficulty items were associated with complications encountered while performing the RCT.</p> <h2>Methodology</h2> <p>One hundred and four general dentists (GDs) and 49 endodontists enrolled 1860 patients needing RCT, April to September 2017. Both before RCT and upon its completion, practitioners used a 10-point scale to rate the RCT's case difficulty (Difficulty Rating [DR]). Then they used a modified Case Difficulty Assessment Form (CDAF) to record the items for difficulty using the form's list of 10 provided choices. We related practitioners' pre-RCT CDAF items to their DR ratings and to the procedural complications that they subsequently experienced during this RCT. General estimating equations (GEE) were used to assess the significance of differences in proportions between GDs and endodontists. Non-parametric tests were used to analyse compositive variables.</p> <h2>Results</h2> <p>Data of 1,698 patients were available for CDAF analyses. The mean CDAF was higher for endodontists than GDs (<i>p</i> &lt; 0.001). Pre- and post-RCT DRs were significantly correlated (<i>r</i> = 0.79, <i>p</i> &lt; 0.001), as were pre-RCT DR and the number of reported CDAF difficulties (<i>r</i> = 0.57, <i>p</i> &lt; 0.001). Overall, practitioners encountered complications in treating 16% of patients. The complications were length of obturation &gt; 2 mm from radiographic apex or beyond apex, canals not negotiable within 2 mm of apex, instrument separation, inadvertent filing/file placement past root apex, and perforation. Several CDAF items were independently predictive of complications. Despite the higher CDAF in teeth treated by endodontists, complications were less frequent among endodontists compared to GDs (13% vs. 19%, <i>p</i> &lt; 0.001).</p> <h2>Conclusions</h2> <p>Pre-RCT assessments predicted intra-operative difficulties and outcomes. Our work underscores the need for targeted assessment tools and specialised training to improve RCT, especially in complex cases treated by GDs.</p> Proteomic Profiling of Dentinal Fluid for the Identification of Biomarkers in Pulpal Inflammation: An Exploratory Study https://onlinelibrary.wiley.com/doi/10.1111/iej.70017?af=R International Endodontic Journal urn:uuid:90835e08-b720-22ca-d686-952695522779 Fri, 15 Aug 2025 05:25:53 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To identify differentially expressed proteins (DEPs) in dentinal fluid across a range of pulpal inflammatory stages—mild, moderate, severe pulpitis—using mass spectrometry.</p> <h2>Methodology</h2> <p>This cross-sectional study analysed dentinal fluid from 60 patients categorised into healthy pulp (control), mild, moderate and severe pulpitis groups, based on Wolters' pulp diagnostic criteria. Pulp conditions were assessed through cold sensibility tests and radiographs, with inclusion limited to patients aged 12–40, who were systemically healthy and exhibited no advanced periodontal or apical pathology. Dentinal fluid was collected under aseptic conditions, stored at −80°C and pooled into 12 representative samples for proteomic analysis. Proteins were extracted using lysis buffers and processed via LC–MS/MS with label-free quantification (LFQ) to identify DEPs. Enrichment analysis and protein–protein interaction (PPI) networks were conducted using Gene Ontology (GO), KEGG databases and STRING, with hub proteins identified using cytoscape. Statistical analysis employed Bayesian t-tests and linear models to evaluate protein expression, with a significance threshold of <i>p</i> &lt; 0.05.</p> <h2>Results</h2> <p>The severe pulpitis group exhibited the highest prevalence of systemic diseases (40%) compared with other groups (6.6%). LC–MS/MS identified 577 proteins, with 62 consistently quantified across the groups. The number of DEPs increased with inflammation severity, with 13 DEPs in severe pulpitis compared with controls. Principal component analysis (PCA) revealed partial separation between control and severe inflammation groups, with significant overlap between mild and moderate stages. Functional enrichment identified key biological pathways, including immune response, energy metabolism and structural integrity. Proteins such as cofilin-1, haemoglobin subunit alpha and peroxiredoxin-1 were upregulated in severe inflammation, while hornerin and myosin light chain 6 were downregulated. These findings highlight proteomic changes associated with pulpitis progression and identify potential prognostic biomarkers and therapeutic targets.</p> <h2>Conclusions</h2> <p>This study identified distinct proteomic differences across pulpitis stages, with unique proteins in severe cases. These findings highlight novel biomarkers for advancing precise, cost-effective, point-of-care diagnostics and therapies, including multiplex platforms or ELISA assays. Proteomic analysis shows promise for understanding disease mechanisms and enabling personalised treatment strategies in endodontics.</p> A Comparative Investigation of Undergraduate Dental Student Stress in the Management of Deep and Moderate Carious Lesions https://onlinelibrary.wiley.com/doi/10.1111/iej.70013?af=R International Endodontic Journal urn:uuid:f69eb49c-0b9c-f009-cedb-fe75fcfd85c9 Wed, 13 Aug 2025 00:00:00 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>The primary objective of this clinical study was to analyse, through physiological and psychological parameters, undergraduate dental student stress during the management of deep compared with moderate carious lesions. Additional objectives aimed to compare student confidence, anxiety and satisfaction during deep and moderate caries management and their perception of the quality of teaching they received regarding these treatments.</p> <h2>Methodology</h2> <p>In this crossover study, 35 clinical students treated deep and moderate caries on permanent vital teeth in adult patients with no history of spontaneous pain. The STAI-State (STAI-S) anxiety questionnaire was completed preoperatively. Stress-VAS (visual analogic scale) and confidence-VAS scores were collected during the preoperative (before anaesthesia), perioperative (end of caries excavation) and postoperative (after patient left) phases of both caries management. Cardiovascular parameters (blood pressure and heart rate) were collected during the same stages. A satisfaction-VAS was completed postoperatively. The effects of the depth of the caries, time and student demographics on preoperative anxiety (STAI-S), pre-, peri- and postoperative stress, confidence, blood pressure and heart rate, as well as postoperative satisfaction, were assessed using Mixed ANOVA with multiple pairwise comparisons. The statistical analysis was performed with IBM SPSS. A questionnaire assessing teaching adequacy was completed after each treatment.</p> <h2>Results</h2> <p>The treatment of deep caries led to a significantly higher level of stress and a significantly lower level of confidence among students than the treatment of moderate caries, pre-, per- and post-operatively (<i>p</i> ≤ 0.05). Student preoperative anxiety was significantly higher in cases of deep caries, and their post-operative satisfaction was significantly lower. However, there was no significant difference between the two groups in terms of cardiovascular parameters at any stage. There was no influence of the student year of study on the parameters examined; however, gender influenced confidence at all times combined, as well as preoperative stress, with females less confident and more stressed than males. The median level of perceived teaching ‘adequacy’ was higher for moderate caries than for deep caries.</p> <h2>Conclusions</h2> <p>Within the limits of this study, the management of deep carious lesions is associated with a higher level of stress among students compared with moderate caries.</p> PFKFB3‐Inhibitor 3PO‐Mediated Glycolytic Reprogramming Promotes Inflammatory Dental Pulp Repair: An In Vitro and In Vivo Study https://onlinelibrary.wiley.com/doi/10.1111/iej.70016?af=R International Endodontic Journal urn:uuid:57e87edb-ada3-12a8-69aa-201cede719cd Mon, 11 Aug 2025 00:00:00 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>This study explores the role of PFKFB3 in pulpitis and its potential as a therapeutic target by modulating glycolytic reprogramming in dental pulp stem cells (DPSCs). Pulpitis, a common inflammatory disease, causes long-term damage to dental structures. Recent evidence suggests that metabolic reprogramming can modulate inflammatory responses and promote tissue repair. This study aims to investigate the anti-inflammatory and reparative effects of glycolysis inhibitors on inflamed dental pulp through in vivo and in vitro experiments.</p> <h2>Methodology</h2> <p>In vitro, hDPSCs were stimulated with lipopolysaccharide (LPS) (1 μg/mL, 3 h) to mimic pulpitis. The effects of the PFKFB3 inhibitor 3PO (10 μM) and siRNA targeting PFKFB3 (50 nM) on glycolysis were assessed using Seahorse analysis, while their impacts on inflammation were evaluated via ELISA and qRT-PCR. A co-culture of DPSCs and macrophages was used to study 3PO's effects on inflammation interactions and glycolytic reprogramming of the inflammatory microenvironment. The influences of 3PO on odontogenic differentiation were examined through qRT-PCR, Western blotting, ALP staining and ARS staining. The related signalling pathways were validated through Western blot (WB) experiments. An SD rat model was employed to validate the in vivo efficacy of 3PO@GelMA pulp capping, and HE staining and immunohistochemistry were used to evaluate the degree of pulp inflammation and reparative dentine formation.</p> <h2>Results</h2> <p>In vitro, LPS elevated glycolytic activity and inflammatory factors (IL-6, IL-1β, TNF-α) in DPSCs. 3PO and si-PFKFB3 mitigated these factors and promoted odontogenic differentiation, evidenced by increased DSPP and ALP expression. Metabolic reprogramming mediated by 3PO and si-PFKFB3, as assessed by Seahorse XF analysis, indicated a shift from glycolysis to oxidative phosphorylation. Additionally, 3PO induced metabolic reprogramming of the co-culture system, reduced the levels of pro-inflammatory cytokines, and promoted the polarisation of macrophages towards the M2 phenotype. PFKFB3 inhibition activated the AMPK/SIRT1/PGC-1α/NF-κB and AMPK/mTOR/NF-κB signalling pathways. In vivo, in the rat pulpitis model, 3PO@GelMA hydrogel application resulted in significantly decreased IL-6 and increased DSPP expression compared to the LPS group (<i>p</i> &lt; 0.001), accompanied by reduced inflammation and enhanced reparative dentine formation.</p> <h2>Conclusion</h2> <p>The PFKFB3 inhibitor 3PO reduces inflammation and promotes reparative dentine formation in pulpitis via metabolic reprogramming and specific signalling pathways, offering a new therapeutic strategy.</p> Dental Undergraduate Student Stress, Anxiety and Confidence in Endodontic Education: A Narrative Review https://onlinelibrary.wiley.com/doi/10.1111/iej.70012?af=R International Endodontic Journal urn:uuid:7e29b0b6-bbc9-b789-0086-94714ad684cb Fri, 08 Aug 2025 04:44:55 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Background</h2> <p>Endodontics is considered a challenging and stressful area by dental practitioners and particularly by dental undergraduate students. Stress or anxiety is prevalent among dental undergraduates, with academic and clinical factors considered the principal sources. In addition, the lowest level of student confidence is generally observed when undertaking complex procedures such as root canal treatment.</p> <h2>Objectives</h2> <p>The aim of this review was to investigate the factors responsible for stress, anxiety and confidence in endodontic education and to identify factors which could potentially moderate undergraduate student stress and enhance confidence, improve well-being before concluding by suggesting potential educational improvements.</p> <h2>Method</h2> <p>A narrative review was performed by searching 3 databases (Pubmed, Web of Science and Scopus). Inclusion criteria were original research reports related to undergraduate dental students' stress, anxiety or confidence in endodontics education. Quantitative, qualitative or mixed-method studies were considered.</p> <h2>Results</h2> <p>This narrative review included 51 studies, which were subdivided into six categories describing factors that have an influence on student stress, anxiety and confidence in endodontics: the patient, the clinical procedure, the academic staff, the teaching methods, the clinical organisation and the student. The management of the endodontic patient's expectations, personality and sometimes acute pain can be stressful for the student. The clinical endodontic procedure, with its complexity and multiple steps, visualisation difficulties and possible complications can also be challenging. Academic staff experienced in endodontics, who are supportive and provide consistent advice, are crucial in managing student stress and anxiety. Educational methods also play an important role in increasing confidence, with a reflective approach, a special focus on hands-on sessions and clinical support with systematic feedback. The clinic should be well-organised and ideally multi-disciplinary, with adequate endodontic equipment and should ensure that the student has sufficient time to practise. Finally, the student's individual stress level is an important factor. The year of training as well as gender should be considered as having an influence on the student stress level.</p> <h2>Conclusions</h2> <p>Undergraduate students find endodontics stressful. Educational improvements in endodontics can contribute to moderating the stress and increasing confidence, while improving endodontic learning and promoting student well-being.</p> Comprehensive Comparative Analysis of the Efficiency of Two Clearing Agents in Natural Transparent Teeth Preparation for Dental Education https://onlinelibrary.wiley.com/doi/10.1111/iej.70005?af=R International Endodontic Journal urn:uuid:97ce6a0b-26d7-6e20-4dd3-0fb1c36d5ba6 Tue, 22 Jul 2025 02:20:29 -0700 International Endodontic Journal, EarlyView. <h2>ABSTRACT</h2> <h2>Aim</h2> <p>To assess the effectiveness of the benzyl benzoate and benzyl alcohol (BABB) solution in transparent teeth preparation compared to methyl salicylate using comprehensive digital and radiographic quantitative values analysis.</p> <h2>Methodology</h2> <p>Freshly extracted 32 single-rooted teeth were immersed in 10% formalin for 24 h. They were then processed following a standard demineralization and dehydration protocol. The teeth were then divided into two groups: the first group, consisting of 12 teeth, was immersed in the BABB solution for 24 h; the second group of 20 teeth underwent the traditional protocol, which involved soaking the teeth in 99% methyl salicylate for the same duration. The optical properties of the processed teeth's translucency were evaluated by transluminant light imaging using a collimated light source and digital camera. Radiographic images of each tooth included in the study, along with a control group consisting of a freshly extracted natural tooth, were acquired under standardised computer settings, exposure conditions and X-ray tube positioning. The segmentation of the radiographic images into superpixels and the selection of areas of interest were conducted in the same manner as with visible light images. Image processing algorithms within the MatLab computational environment were utilised to assess the colour and intensity of the translucent light at the apical region of the root for each tooth.</p> <h2>Results</h2> <p>The optical properties of selected anatomical locations were consistent across both groups of teeth when evaluating hue, saturation and value of pixels. The X-ray absorption in the translucent teeth was significantly lower than that in the non-translucent teeth, with notable differences observed between the groups; specifically, teeth affected by BABB material exhibited greater permeability to X-rays than those affected by methyl salicylate.</p> <h2>Conclusions</h2> <p>The BABB solution demonstrates comparable efficacy to methyl salicylate regarding the optical properties of translucent teeth. When examining X-ray absorption, teeth treated with the BABB solution exhibited greater permeability to X-ray absorption than those treated with methyl salicylate.</p>