ABSTRACT:Cannabidiol (CBD) has both analgesic and anti-inflammatory properties. Because CBD is not psychotomimetic, it could be an excellent nonopioid alternative for various pain disorders. The aim was to assess the effectiveness of CBD as an analgesic for apical periodontitis-induced mechanical hypersensitivity (MH), its site of action (peripheral or central), and the potential involvement of transient receptor potential vanilloid 1 (TRPV1), using a mouse behavioral model of apical periodontitis (AP). Male and female mice underwent pulp exposure of the left maxillary first molar (AP group) or sham surgery (Sham group). Mechanical hypersensitivity was assessed 21 days after surgery using von Frey filaments on the left vibrissal pad. Apical periodontitis mice that received a single dose of oral CBD (AP [CBD]) experienced a significant reduction in MH at 45 minutes and 120 minutes compared with AP mice that received vehicle (AP [Veh]). The analgesic effect in males was significantly greater than in females at this CBD dose. Intrathecal and intracisternal (IC), but not ipsilateral intraoral, CBD injections reduced MH in the male AP (CBD) group, indicating a central site of action of CBD in this model of odontogenic pain. Furthermore, intraperitoneal and IC injection of AMG 517 (TRPV1 antagonist) before an oral CBD dose blocked the CBD analgesic effect in male mice, suggesting TRPV1's involvement. Overall, this study shows, for the first time, that oral CBD can be an effective analgesic for apical periodontitis-induced MH. This analgesic effect was mediated through a central site of action and involved the TRPV1 channel.

OBJECTIVE:This retrospective pragmatic study aimed to evaluate and compare the healing outcomes of the multisonic GentleWave irrigation system with conventional syringe-needle irrigation used for non-surgical endodontic treatment. METHODS:The study included 46 teeth that underwent nonsurgical endodontic treatment using two different irrigation protocols: (1) GentleWave irrigation system, and (2) Conventional syringe-needle irrigation, with a minimum follow-up of 1 year. Preoperative and follow-up data from treatment records, including clinical signs and symptoms, periapical radiographs, and cone-beam computed tomography (CBCT) images when available, were collected. Two independent evaluators scored the radiographs and CBCT scans based on the 2D periapical index (PAI) and 3D CBCT-PAI index, respectively. Based on clinical data and radiographic evaluation, treatment outcomes were categorized as healed, healing, or diseased. The success rate was assessed using both strict and loose criteria. Statistical analyses included Fisher's exact tests, and Wilcoxon rank-sum tests, where appropriate. The significance level was set at 0.05. RESULTS:Based on the periapical index and clinical evaluation, both the GentleWave and conventional groups exhibited comparable percentages of healed cases, corresponding to success rates of 69% and 70%, respectively (strict criteria). Using loose criteria, the success rate based on periapical imaging was 96% for conventional and 85% for GW groups. No statistically significant difference in healing outcomes/success rate was observed between the groups on both periapical radiograph and CBCT interpretation. Male sex, negative pulp vitality, presence of pre-operative periapical radiolucency (PARL), and absence of pre-operative symptoms were associated with reduced healing in the Conventional group. Pre-operative PARL and non-surgical root canal retreatment were associated with reduced healing in the GW group. CONCLUSION:There were no differences in success rates or healing outcomes of endodontic treatment between the GentleWave irrigation system and conventional syringe-needle irrigation at 12-month follow-up. The presence of pre-operative PARL was significantly correlated with reduced success in both groups. CLINICAL RELEVANCE:This study highlights similar success rates and healing outcomes for endodontic treatment with the GentleWave irrigation system compared to conventional syringe-needle irrigation at 12 months follow-up.

INTRODUCTION:The American Association of Endodontics (AAE) Regenerative Endodontics Committee reports here the web-based survey data of regenerative endodontic procedures performed by the AAE members from 2008 to 2019. METHODS:The web-based survey consisted of 2 questionnaires, a revascularization and a follow-up, including clinical and radiographic data at 3, 6, 12 or >12 months after treatment. Data from demographics, etiology, clinical protocols, radiographic, and clinical outcome as perceived by the clinicians were recorded. From 927 entries, 184 full cases were submitted and 126 were suitable for radiographic analysis. The data were divided into cases with 6-12 months and cases with >12 months recall time. Descriptive statistics and univariate analyses were performed. RESULTS:Predominantly patients were male (63%), average 10 years-old with anterior teeth (77.2%) due to trauma (69.6%). A wide variation in regenerative endodontic procedures protocols was reported by the AAE members. The most common clinical protocols used minimal instrumentation (75.5%), 2.5% or higher concentrations of sodium hypochlorite (83.7%), and antibiotic paste as intracanal medication (58.7%). The majority reported blood clot formation (56%) and most common coronal capping material was white mineral trioxide aggregates (50.5%). Increases in radiographic root length, and radiographic root area were proportional to the time lapsed after treatment. Overall, case outcomes were categorized by clinicians as successful (54.3%), uncertain (23.9%), and unsuccessful (3.8%). CONCLUSIONS:This web-based survey provides a valuable perspective on case selection, clinical protocols, and perceived outcomes for regenerative endodontic procedures and supports the need for future higher level evidence studies.

The aim of this study was to evaluate the cytocompatibility of an herbal extract compound oral rinse [StellaLife VEGA (SLife)] against relevant human cellular models of oral surgical wound healing. SL was compared to the gold standard for peri-/post-operative oral surgical use, i.e., Chlorhexidine (CHX) and to a commonly utilized essential-oil (EO) based antiseptic rinse. Fibroblasts and primary oral stem cells of the apical papilla (SCAPs) were employed to assess its comparative cytotoxicity to the active comparator antiseptic rinses and its effects on wound healing in vitro. In cytotoxicity assays, multiple timepoints were tested ranging from clinically relevant of 60-s rinsing to protracted challenge of up to 5 min, to determine dose-dependent toxicity. The SLife group consistently demonstrated minimal cytotoxicity as compared to active comparators across experimental timepoints and different cells lines. At concentrations up to 20% v/v SLife-challenged fibroblasts and SCAPs demonstrated no significant toxicity as compared to unstimulated controls (p > 0.05). When assessing wound healing, a scratch wound assay revealed significantly accelerated cell migration for SLife as compared to CHX (p < 0.05). Notably, all active comparator antiseptic rinses affected wound healing responses by significantly reducing total collagen deposition after intermittent "rinsing" intervals that simulated post-surgical oral rinsing. Nonetheless, intermittent as well as continuous challenge of cells with SLife had a positive effect in functional collagen assays. An herbal extract compound-based oral rinse was found to be cytocompatible to cells critical to oral wound healing and to promote fibroblast migration and differentiation, contrary to existing antiseptic rinses that lack selective cytotoxicity.

INTRODUCTION:Factors that influence clinical outcomes for regenerative endodontic procedures (REPs) are unknown. This retrospective study aimed to assess tooth healing, root development, pulp vitality, and esthetics post-REPs and categorize them into clinician- and patient-centered outcomes. Furthermore, this study identified significant predictors affecting such outcomes.METHODS:Immature permanent teeth diagnosed with pulp necrosis treated with REPs between 2008 and 2018 with a minimum of 1-year follow-up were included. Outcomes included success and survival rates, changes in root development using 2-dimensional radiographic root area (RRA) and 3-dimensional measurements, pulp vitality, and tooth discoloration. Predictor variables of success included age, sex, etiology of pulp necrosis (PN), type of medicament, sodium hypochlorite (NaOCl) concentration, type of biomaterial used over the blood clot, and preoperative apical diagnosis. Statistical analyses included Cox proportional hazard analyses and generalized regression models.RESULTS:Fifty-one teeth with an average of 2.1 years of follow-up satisfied the criteria. The survival rate was 92%. The success rate was 84.3% with age, etiology of PN, type of medicament, and NaOCl concentration being significant predictors of failure. Root development occurred in 91.4% of cases with age, sex, etiology of PN, type of medicament, NaOCl concentration, and apical diagnosis being significant predictors for RRA change. Positive pulp sensibility responses were associated with greater RRA change, and, finally, the type of biomaterial was a significant predictor for tooth discoloration after treatment.CONCLUSIONS:REPs provide a high survival rate. Patient and clinical factors may affect outcomes, and this knowledge may help to define the criteria for optimal treatment planning of REPs.

Peri-implantitis is becoming a frequent complication observed around dental implants. An endodontic infection of a nearby tooth or an immediate implant placement in an inflamed bone socket from failing endodontic therapy has been associated with retrograde peri-implantitis (RPI), a condition that presents with radiographic lucency at the "apex" of an implant. However, current classification schemes do not capture endodontic lesions that may manifest as coronal or intrabony lesions associated with dental implants. As a result, such cases may be mistreated. Here we present for the first time 2 cases in which peri-implant bone loss occurred in the coronal half of the implant adjacent to a tooth with an endodontic-periodontic lesion and was resolved via endodontic therapy or tooth extraction as indicated. This proof of concept report aimed to introduce endodontic peri-implant ("endo-implant") defects and increase vigilance, which may help prevent overtreatment or mistreatment of such cases.

IntroductionPatients seeking endodontic treatment commonly present with reduced mechanical pain thresholds (ie, mechanical allodynia [MA]) in the offending teeth. In patients with moderate to severe pain, MA may manifest in the teeth contralateral to the offending teeth because of the onset of central sensitization (CS). We hypothesize that there are quantitative differences in MA and CS in patients with different pulp and periradicular diagnoses.MethodsPatients (n = 70) receiving endodontic treatment in the graduate endodontic clinic at the University of Texas Health Science Center at San Antonio and healthy volunteers (n = 10) were included in this cross-sectional study. The mechanical pain threshold from molar teeth was measured by a digital bite force transducer on the offending tooth (ipsilateral) and the contralateral tooth. Ipsi- and contralateral MA among different endodontic diagnoses were analyzed using the Kruskal-Wallis with Dunn post hoc test and the Student t test for differences between sexes. Multivariate regression models analyzed predictors for MA and CS.ResultsPeriradicular diagnoses of asymptomatic apical periodontitis, symptomatic apical periodontitis, and chronic apical abscess cases were significantly associated with MA. CS, seen as contralateral MA, was only detected in pulpal diagnosis of symptomatic irreversible pulpitis, previously initiated treatment, symptomatic apical periodontitis, and chronic apical abscess. Females experienced significantly lower pain thresholds than males on both sides. MA and CS were significantly correlated in both sexes. The preoperative pain level and duration were significant predictors for MA and CS only in female patients. Lastly, age was a significant predictor for MA in females.ConclusionsThe magnitude of MA and CS varied with different endodontic diagnoses, with CS being correlated with increases in MA. Only in female patients were age, preoperative pain duration, and intensity significant predictors for the development of MA and CS.

Introduction: Regeneration of the pulp-dentin complex is the penultimate goal of regenerative endodontic procedures (REPs). Histological outcomes have demonstrated reparative tissue formation in human teeth extracted post-REPs. However, lack of accurate characterization has precluded identification of the true nature of tissues formed post-REP. Methods: Here, we present 2 case reports of tooth #29 and #9 treated with REPs and demonstrate their clinical, radiographic, and histological outcomes. Results: Clinical outcomes revealed healing of apical periodontitis in both teeth and re-establishment of vitality responses in tooth #29. Moreover, radiographic assessments using 2D and 3D-volumetric analyses demonstrate considerable increase in root development for both teeth. Further, histological outcomes evaluated using Hematoxylin and Eosin and immuno-histochemical staining demonstrates presence of vascular and lymphatic structures as well as immune cell markers indicative of regeneration of an immuno-competent pulp. Lastly, examination of hard tissue deposition shows dentin-like tissue in parts of tooth #29 demonstrating for the first time, regeneration of a pulp-dentin complex post-REP. Conclusions: Collectively, this is the first study demonstrating recapitulation of several tissues commonly found as part of a pulp-dentin complex in teeth treated with REPs.

Background Following the economic crisis in Greece in 2010, the country's ongoing austerity measures include a substantial contraction of health-care expenditure, with reports of subsequent negative health consequences. A comprehensive evaluation of mortality and morbidity is required to understand the current challenges of public health in Greece. Methods We used the results of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 to describe the patterns of death and disability among those living in Greece from 2000 to 2010 (pre-austerity) and 2010 to 2016 (post-austerity), and compared trends in health outcomes and health expenditure to those in Cyprus and western Europe. We estimated all-cause mortality from vital registration data, and we calculated cause-specific deaths and years of life lost. Age-standardised mortality rates were compared using the annualised rate of change (ARC). Mortality risk factors were assessed using a comparative risk assessment framework for 84 risk factors and clusters to calculative summary exposure values and population attributable fraction statistics. We assessed the association between trends in total, government, out-of-pocket, and prepaid public health expenditure and all-cause mortality with a segmented correlation analysis. Findings All-age mortality in Greece increased from 944.5 (95% uncertainty interval [UI] 923.1-964.5) deaths per 100 000 in 2000 to 997.8 (975.4-1018) in 2010 and 1174.9 (1107.4-1243.2) in 2016, with a higher ARC after 2010 and the introduction of austerity (2.72% [1.65 to 3.74] for 2010-16) than before (0.55% [0.24 to 0.85] for 2000-10) or in western Europe during the same period (0.86% [0.54 to 1.17]). Age-standardised reduction in ARC approximately halved from 2000-10 (-1.61 [95% UI -1.91 to -1.30]) to 2010-16 (-0.87% [-2.03 to 0.20]), with post-2010 ARC similar to that in Cyprus (-0.86% [-1.4 to -0.36]) and lower than in western Europe (-1.14% [-1.48 to -0.81]). Mortality changes in Greece coincided with a rapid decrease in government health expenditure, but also with aggregate population ageing from 2010 to 2016 that was faster than observed in Cyprus. Causes of death that increased were largely those that are responsive to health care. Comparable temporal and age patterns were noted for non-fatal health outcomes, with a somewhat faster rise in years lived with disability since 2010 in Greece compared with Cyprus and western Europe. Risk factor exposures, especially high body-mass index, smoking, and alcohol use, explained much of the mortality increase in Greek adults aged 15-49 years, but only explained a minority of that in adults older than 70 years. Interpretation The findings of increases in total deaths and accelerated population ageing call for specific focus from health policy makers to ensure the health-care system is equipped to meet the needs of the people in Greece. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.

The objective of this review is to provide an overview of the past and present advancements in regenerative endodontics.

Introduction: Cone-beam computed tomographic (CBCT) analysis allows for 3-dimensional assessment of periradicular lesions and may facilitate preoperative periapical cyst screening. The purpose of this study was to develop and assess the predictive validity of a cyst screening method based on CBCT volumetric analysis alone or combined with designated radiologic criteria.Methods: Three independent examiners evaluated 118 presurgical CBCT scans from cases that underwent apicoectomies and had an accompanying gold standard histopathological diagnosis of either a cyst or granuloma. Lesion volume, density, and specific radio logic characteristics were assessed using specialized software. Logistic regression models with histopathological diagnosis as the dependent variable were constructed for cyst prediction, and receiver operating characteristic curves were used to assess the predictive validity of the models. A conditional inference binary decision tree based on a recursive partitioning algorithm was constructed to facilitate preoperative screening.Results: Interobserver agreement was excellent for volume and density, but it varied from poor to good for the radiologic criteria. Volume and root displacement were strong predictors for cyst screening in all analyses. The binary decision tree classifier determined that if the volume of the lesion was > 247 mm(3), there was 80% probability of a cyst. If volume was < 247 mm(3) and root displacement was present, cyst probability was 60% (78% accuracy).Conclusions: The good accuracy and high specificity of the decision tree classifier renders it a useful preoperative cyst screening tool that can aid in clinical decision making but not a substitute for definitive histopathological diagnosis after biopsy. Confirmatory studies are required to validate the present findings.

Introduction Apical papilla represents a source of an enriched mesenchymal stem cell (MSC) population (stem cells of the apical papilla [SCAPs]) that modulates root development and may participate in regenerative endodontic procedures in immature teeth with pulp necrosis. The characteristics and phenotype of this tissue in the presence of inflammation are largely unknown. The purpose of this study was to characterize a human apical papilla sample that was isolated from an immature tooth with pulp necrosis and apical periodontitis. Methods Inflamed periapical tissue that included part of the apical papilla (apical papilla clinical sample [CS]) was collected from an immature mandibular premolar previously diagnosed with pulp necrosis and apical periodontitis during an apexification procedure. Harvested cells from this tissue (SCAP CS) were compared with inflamed periapical progenitor cells (IPAPCs) and normal SCAP (SCAP-RP89) in flow cytometry and quantitative osteogenesis experiments. Part of the issue was further processed for immunohistochemistry and compared with apical papilla and coronal pulp sections from normal immature teeth as well as inflamed periapical tissues from mature teeth. Results Similar to SCAP-RP89, 96.6% of the SCAP CS coexpressed the MSC markers CD73, CD90, and CD105, whereas only 66.3% of IPAPCs coexpressed all markers. The SCAP CS showed a significantly greater mineralization potential than both SCAP-RP89 and IPAPCs. Finally, immunohistochemical analysis revealed moderate infiltration of cells expressing the inflammatory markers CD45/68 in the apical papilla CS and prominent CD24, CD105, and von Willebrand factor expression. Conclusions Under inflammatory conditions, human apical papilla was found moderately inflamed with retained SCAP vitality and stemness and increased osteogenic and angiogenesis potential.

Background & aims: The deleterious effect of cariogenic dietary patterns on tooth loss is well characterized, but the contribution of diet-borne systemic inflammation to loss of teeth remains uncharted. Recent efforts have unveiled a protective role of single nutrients to periodontal health. However, the assessment of overall diet as a modifiable risk factor for oral health remains elusive. Thus, the aim of this study was to assess the association between diet-borne systemic inflammation and tooth loss in a representative sample of the US adult non-institutionalized population. Methods: A cross-sectional analysis of a sample of participants of the 2009-2010 and 2011-2012 continuous NHANES receiving an oral exam and providing dietary recall data was performed. Dietary inflammatory potential was assessed by the Dietary Inflammatory Index (DH), a composite measure computed based on the association between nutrients and systemic pro-inflammatory cytokine levels. The outcome measure was prevalent tooth loss. Numbers of missing teeth were regressed across quartiles of the DH using multivariable linear regression models. Results: 6887 eligible NHANES participants were included in the analysis; participants in the highest quartile of the DH index (pro-inflammatory diet) had an average [95% CI] of 0.84 [0.24, 1.45] additional more teeth lost as compared to those in the lowest quartile of DH (anti-inflammatory diet) (p = 0.015), after adjusting for known confounders. This significant association remained in subgroup analyses, including the lowest tertiles of energy-adjusted carbohydrate intake, and in persons aged >= 50 years. Conclusions: Adherence to an anti-inflammatory diet is associated with fewer missing teeth. These results suggest protective dietary patterns as a modifiable protective factor for tooth loss in the US adult population and support the incorporation of tooth loss prevention in the agenda of dietary public health interventions to prevent chronic inflammatory diseases. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

ABSTRACT Objective: The aim of the present study was to evaluate and compare the cytotoxic effects of Biodentine and MTA on dental pulp stem cells (DPSCs) and to assess cell viability and adherence after material exposure to an acidic environment. Material and Methods: DPSCs were cultured either alone or in contact with either: Biodentine; MTA set for 1 hour; or MTA set for 24 hours. After 4 and 7 days, cell viability was measured using the MTT assay. Biodentine and MTA were also prepared and packed into standardized bovine dentin disks and divided into three groups according to the storage media (n=6/group): freshly mixed materials without storage medium (Group A); materials stored in saline (Group B); materials stored in citric acid buffered at pH 5.4 (Group C). After 24 hours, DPSCs were introduced in the wells and cell adherence, viability, and cellular morphology were observed via confocal microscopy after three days of culture. Cell viability was analyzed using repeated-measures analysis of variance test with Tukey's post hoc tests (α=0.05). Results: Biodentine expressed significantly higher cell viability compared with all other groups after 4 days, with no differences after 7 days. Notably, cell viability was significantly greater in 24-hour set MTA compared with 1-hour set MTA and control groups after 7 days. Material exposure to an acidic environment showed an increase in cell adherence and viability in both groups. Conclusions: Biodentine induced a significantly accelerated cell proliferation compared with MTA. Setting of these materials in the presence of citric acid enhanced DPSC viability and adherence.

Introduction: Regenerative endodontic procedures (REPs) are viable alternatives for treating immature teeth, yet these procedures do not predictably lead to pulp-dentin regeneration. A true bioengineering approach for dental pulp regeneration requires the incorporation of a scaffold conducive with the regeneration of the pulp-dentin complex. Several materials have been proposed as scaffolds for REPs; nonetheless, the majority are not eligible for immediate clinical chairside use. Thus, the aim of this study was to evaluate Restylane, a Food and Drug Administration-approved hyaluronic acid based gel, as possible scaffold for REPs. Methods: Stem cells of the apical papilla (SCAP) were cultured either alone or in mixtures with either Restylane or Matrigel scaffolds. Groups were cultured in basal culture medium for 6, 24, and 72 hours, and cell viability was assessed. For the mineralizing differentiation experiments, groups were cultured in differentiation medium either for 7 days and processed for alkaline phosphatase activity or for 14 days and processed for gene expression by using quantitative reverse-transcription polymerase chain reaction. SCAP in basal medium served as control. Results: Cell encapsulation in either Restylane or Matrigel demonstrated reduced cell viability compared with control. Nonetheless, cell viability significantly increased in the Restylane group in the course of 3 days, whereas it decreased significantly" in the Matrigel group. Restylane promoted significantly greater alkaline phosphatase activity and upregulation of dentin sialophosphoprotein, dentin matrix acidic phosphoprotein-1, and matrix extracellular phosphoglycoprotein, compared with control. Conclusions: A Food and Drug Administration-approved hyaluronic acid based injectable gel promoted SCAP survival, mineralization, and differentiation into an odontoblastic phenotype and may be a promising scaffold material for REPs.

Edentulism is associated with various adverse health outcomes but treatment options in low- and middle-income countries (LMICs) are limited. Data on its prevalence and its effect on mental health and overall-health is lacking, especially from LMICs. Self-reported data on complete edentulism obtained by standardized questionnaires on 201,953 adults aged ≥18 years from 50 countries which participated in the World Health Survey (WHS) 2002–2004 were analyzed. Age and sex-standarized edentulism prevalence ranged from 0.1% (95% CI = 0.0–0.3) (Myanmar) to 14.5% (95% CI = 13.1–15.9) (Zimbabwe), and 2.1% (95% CI = 1.5–3.0) (Ghana) to 32.3% (95% CI = 29.0–35.8) (Brazil) in the younger and older age groups respectively. Edentulism was significantly associated with depression (OR 1.57, 95% CI = 1.23–2.00) and poor self-rated health (OR 1.38, 95% CI = 1.03–1.83) in the younger group with no significant associations in the older age group. Our findings highlight the edentulism-related health loss in younger persons from LMICs. The relative burden of edentulism is likely to grow as populations age and live longer. Given its life-long nature and common risk factors with other NCDs, edentulism surveillance and prevention should be an integral part of the global agenda of NCD control.

The goal of regenerative dentistry is to induce biologic replacement of dental tissues and their supporting structures. Regenerative endodontics is a new field within the specialty of endodontics that focuses on promoting the physiological and functional regeneration of the damaged pulp-dentin complex. Periodontitis is among the most prevalent inflammatory diseases affecting almost half of the U.S. adult population and, if left untreated, is the leading cause of tooth loss in adulthood. Periodontal regenerative therapy has been developed under the premise of regenerating the lost periodontal structures, given that the inflammation is controlled. Bone grafts are widely used as a therapeutic strategy to enhance periodontal regeneration. Guided tissue regeneration (GTR) is a distinctly different approach that aims to regenerate a new periodontal apparatus on a previously diseased root surface. Combination of different periodontal regeneration therapies has been shown to enhance clinical outcomes. One of the most common therapies is combination of osseous grafting with GTR.

Regenerative endodontic procedures are stem cell-based treatments for immature teeth with pulp necrosis. The translation of regenerative endodontic procedures into treating mature teeth depends, among other factors, on the availability and delivery of mesenchymal stem cells (MSCs) into the root canal system. The aim of this clinical study was to evaluate whether evoked bleeding from the periapical tissues elicits the influx of MSCs into the root canal system in mature teeth with apical lesions. Participants included in this study (N = 20) were referred for endodontic treatment of mature teeth with apical lesions. Following chemomechanical debridement, intracanal bleeding from the periapical tissues was achieved, and intracanal blood samples were collected. A positive blood aspirate was also collected in the cartridges during local anesthesia. Total RNA was isolated and used as a template in quantitative reverse transcription polymerase chain reactions using MSC-specific arrays. Data were analyzed with the Wilcoxon signed-rank test, and correlation between gene expression and sex or age was tested with Spearman's rank correlation coefficient test. In addition, MSCs were isolated from an intracanal bleeding sample and subjected to flow cytometry and quantitative osteogenesis assay. Last, the presence and distribution of MSCs within periradicular lesions were evaluated with immunohistochemistry (n = 4). The MSC markers CD73, CD90, CD105, and CD146 were significantly upregulated, with median fold change values of 2.9, 31.7, 4.6, and 6.8, respectively. Conversely, the negative marker for MSCs, CD45, was significantly downregulated (median, -2.7). There was no correlation with age, sex, tooth type, or treatment for any of the evaluated genes. Isolated intracanal cells coexpressed MSC markers and demonstrated robust mineralizing differentiation potential. Finally, immunohistochemical analysis revealed that MSCs were found compartmentalized mainly within vasculature structures located in periapical lesions. Collectively, findings indicate that the evoked-bleeding technique delivers MSCs into the root canal system in mature teeth with apical lesions.