Does the use of different scaffolds have an impact on the therapeutic efficacy of regenerative endodontic procedures? A systematic evaluation and meta-analysis.

BACKGROUND: In the regenerative endodontic procedures, scaffolds could influence the prognosis of affected teeth. Currently, there is controversy regarding the postoperative evaluation of various scaffolds for pulp regeneration. The objective of this study was to access whether other scaffolds, used alone or in combination with blood clot (BC), are more effective than BC in regenerative endodontic procedures. METHODS: We systematically search the PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Google Scholar databases. Randomized controlled trials examining the use of BC and other scaffold materials in the regenerative endodontic procedures were included. A random effects model was used for the meta-analysis. The GRADE method was used to determine the quality of the evidence. RESULTS: We screened 168 RCTs related to young permanent tooth pulp necrosis through electronic and manual retrieval. A total of 28 RCTs were related to regenerative endodontic procedures. Ultimately, 12 articles met the inclusion criteria and were included in the relevant meta-analysis. Only 2 studies were assessed to have a low risk of bias. High quality evidence indicated that there was no statistically significant difference in the success rate between the two groups (RR=0.99, 95% CI=0.96 to 1.03; 434 participants, 12 studies); low-quality evidence indicated that there was no statistically significant difference in the increase in root length or root canal wall thickness between the two groups. Medium quality evidence indicated that there was no statistically significant difference in pulp vitality testing between the two groups. CONCLUSIONS: For clinical regenerative endodontic procedures, the most commonly used scaffolds include BC, PRP, and PRF. All the different scaffolds had fairly high clinical success rates, and the difference was not significant. For regenerative endodontic procedures involving young permanent teeth with pulp necrosis, clinical practitioners could choose a reasonable scaffold considering the conditions of the equipment and patients.

Characterization of cells in blood evoked from periapical tissues in immature teeth with pulp necrosis and their potential for autologous cell therapy in Regenerative Endodontics.

OBJECTIVE: The objectives of this study were to isolate, characterize progenitor cells from blood in the root canals of necrotic immature permanent teeth evoked from periapical tissues and evaluate the applicable potential of these isolated cells in Regenerative Endodontics. DESIGN: Ten necrotic immature permanent teeth from seven patients were included. Evoked bleeding from periapical tissues was induced after chemical instrumentation of the root canals. Cells were isolated from the canal blood and evaluated for cell surface marker expression, multilineage differentiation potential, proliferation ability, and target protein expression. Cell sheets formed from these cells were transferred into human root segments, and then transplanted into nude mice. Histological examination was performed after eight weeks. Data analysis was conducted using one-way ANOVA followed by Tukey's post-hoc comparison, considering p < 0.05 as statistically significant. RESULTS: The isolated cells exhibited characteristics typical of fibroblastic cells with colony-forming efficiency, and displayed Ki67 positivity and robust proliferation. Flow cytometry data demonstrated that at passage 3, these cells were positive for CD73, CD90, CD105, CD146, and negative for CD34 and CD45. Vimentin expression indicated a mesenchymal origin. Under differentiation media specific differentiation media, the cells demonstrated osteogenic, adipogenic, and chondrogenic differentiation potential. Subcutaneous root canals with cell sheets of isolated cells in nude mice showed the formation of pulp-like tissues. CONCLUSIONS: This study confirmed the presence of progenitor cells in root canals following evoked bleeding from periapical tissues of necrotic immature teeth. Isolated cells exhibited similar immunophenotype and regenerative potential with dental mesenchymal stromal cells in regenerative endodontic therapy.

A retrospective cohort study of pulp prognosis in luxated permanent teeth: a competing risk analysis.

AIM: The present retrospective cohort study aimed to evaluate luxated permanent teeth for pulp prognosis and risk factors. METHODOLOGY: Case records and radiographs of 224 patients, involving 427 luxated permanent teeth, referred for treatment at the Dental Trauma Center-School of Dentistry, Universidade Federal de Minas Gerais, (DTC-SD-UFMG) from 2014 to 2022, were assessed for pulp prognosis classified as vitality, necrosis and pulp canal obliteration (PCO). A competing risk survival analysis estimated the hazards of the three outcomes, and the effect of demographic, clinical and treatment variables was tested using a cause specific Cox regression model. RESULTS: Pulp vitality was found in163 teeth (38.2%), pulp necrosis in 120 teeth (28.1%) and 55 teeth (12.9%) developed PCO. Pulp vitality decreased in the presence of concomitant crown fractures (HR 0.38 95% CI [0.2-0.8] p = 0.006). The risk of pulp necrosis (HR 0.62 95% CI [0.4-0.96] p = 0.03) was lower in cases with open apices but increased with concomitant crown fractures (HR 4.0 95% CI [2.6-6.1] p = 0.001) and intrusions (HR 2.3 95% CI [1.2-4.1] p = 0.007). Lateral or extrusive luxations (HR 3.0 95% CI [1.3-6.9] p = 0.001) and open apices (HR 2.4 95% CI [1.2-4.7] p = 0.01) showed higher rates of PCO. CONCLUSION: Type of luxation, the diameter of the apical foramen, and the presence of concomitant crown fractures were main determinants of pulp prognosis after luxation injuries in permanent teeth. CLINICAL RELEVANCE: Pulp prognosis after tooth luxation is dependent on the presence and direction of tooth displacement together with infection control. CLINICAL TRIAL REGISTRATION: Not applicable.

Correlation between pulp sensibility and magnetic resonance signal intensity following regenerative endodontic procedures in mature necrotic teeth- a retrospective cohort study.

BACKGROUND: With increasing studies being published on regenerative endodontic procedures (REPs) as a treatment modality for mature necrotic teeth, the assessment of outcomes following regenerative endodontic procedures has become more challenging and the demand for a better understanding of the regenerated tissues following this treatment is rising. The study aimed to correlate cold, electric pulp testing (EPT), and magnetic resonance imaging (MRI) signal intensity (SI) in mature necrotic teeth treated with regenerative endodontic procedures. METHODOLOGY: This retrospective cohort study included eighteen adult patients who experienced tooth necrosis in mature maxillary anterior teeth recruited from the outpatient clinic, Conservative Dentistry Department, Faculty of Dentistry, Alexandria University, Alexandria, Egypt from July 2017 until December 2018 with 12 months of follow-up. regenerative endodontic procedures via blood clot were performed. The canals were instrumented by ProTaper Next (PTN) files until final sizes X3 or X5. Biodentine was used as cervical plug material. Pre and post-operative clinical follow-up was done where the patients' responses to cold and electric pulp testing were given a scoring system and were compared to the normal contralateral tooth. Pre and post-operative magnetic resonance imaging signal intensity of both the involved tooth and its contralateral at the middle and the apical thirds of the root canals were assessed after 3, 6, and 12 months. Data was analyzed using the ANOVA, Friedman and Bonferroni tests. Significance was set at a p-value < 0.05. RESULTS: All 18 teeth scored a baseline score of "2" for cold and electric pulp testing. There was a significant difference between scores of the cold test at baseline and 12-month follow-up (p < 0.001). There was a significant difference between scores of the electric pulp testing of baseline and 12-month follow-up (p < 0.001). There was a moderately significant indirect (inverse) correlation between magnetic resonance imaging signal intensity and cold test in both the middle and apical thirds at 12 months. No significant correlations were detected between magnetic resonance imaging signal intensity and electric pulp testingat any of the time intervals (p > 0.05). CONCLUSION: Magnetic resonance imaging is a successful non-invasive method to assess outcomes of regenerative endodontic procedures and correlating it with another reliable method of assessing pulpal responses, cold test, could validate these outcomes. CLINICAL TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (ID: NCT03804450).

Failed Regenerative Endodontic Case Treated by Modified Aspiration-irrigation Technique and Apexification.

AIM: This report addresses the management of a large persistent discharging lesion in an 11-year-old boy. The report describes the use of aspiration-irrigation technique for the management of immature necrotic tooth with persistent discharge after a failed regenerative procedure. BACKGROUND: Regenerative endodontics aim to provide an increase in root canal width, length, and in apical closure. Alternative procedures, such as apexification, should be attempted when regeneration fails. If the canal cannot be dried to persistent discharge, the aspiration-irrigation technique can be used. The technique relies on using aspiration along with irrigation to remove pus from the periapical area. CASE DESCRIPTION: This is a case for an 11-year-old patient who had trauma to tooth #11, which resulted in the complicated crown fracture. He had an emergency management that included pulpectomy and intracanal medication at another clinic. Two years later, the patient was presented to our clinic. Upon examination, the diagnosis was previously initiated therapy with asymptomatic apical periodontitis in immature tooth #11. Regeneration was attempted first but failed. The mineral trioxide aggregate (MTA) plug was removed, and the canal had persistent pus discharge. The canal was filled with intracanal medication, and then 2 weeks later, the canal was filled with triple antibiotic paste (TAP). Next visit, and due to continuous discharge, tooth #11 was treated conservatively with an intracanal aspiration-irrigation technique. An IrriFlex needle attached to a high-volume suction was used to aspirate the cystic fluid. Mineral trioxide aggregate plug apexification was performed in a later visit and the tooth was restored. CONCLUSION: During the 3-month and 16-month follow-up, there was resolution of the symptoms, a decrease in the periapical lesion size, and soft tissues appeared within normal limits. CLINICAL SIGNIFICANCE: Regenerative procedures are a good option for immature necrotic teeth. These procedures may fail due to persistent pus discharge from the root canals. The aspiration-irrigation technique is a good treatment option in cases of consciously discharging canals. How to cite this article: Alsofi L, Almarzouki S. Failed Regenerative Endodontic Case Treated by Modified Aspiration-irrigation Technique and Apexification. J Contemp Dent Pract 2024;25(1):92-97.

Allogeneic Bone Marrow Mesenchymal Stromal Cell Transplantation Induces Dentin Pulp Complex-like Formation in Immature Teeth with Pulp Necrosis and Apical Periodontitis.

INTRODUCTION: Dental pulp regeneration is challenging in endodontics. Cellular therapy is an alternative approach to induce dental pulp regeneration. Mesenchymal stromal cells (MSCs) have the capacity to induce dental pulp-like tissue formation. In this study, we evaluated the capacity of allogeneic bone marrow MSCs (BM-MSCs) to regenerate pulp following necrosis and apical periodontitis in children's permanent immature apex teeth. METHODS: Patients aged 8 to 12 years with pulp necrosis and apical periodontitis were evaluated. The study included 15 teeth (13 incisors and 2 molars) from 14 patients (8 boys and 6 girls). Radiographic evaluation showed periapical radiolucency and immature apex teeth. There was no response to cold or electric pulp testing. The root canal of each tooth was cleaned, shaped, and Ca(OH)2 used as an interappointment medication. Cryopreserved allogeneic BM-MSCs were thawed, expanded, incorporated into preclotted platelet-rich plasma, and implanted into the tooth's pulp cavity. They were sealed with bioceramic cement and composite. Sensibility, apical foramen, calcium deposits within the root canal, and resolution of periapical lesions were evaluated in each tooth over the following 12 months. RESULTS: Based on 9 variables established for dental pulp-like tissue regeneration, all MSC-treated teeth showed evidence of successful regeneration. Clinical and radiographic evaluation of the treated teeth showed periapical lesion healing, sensitivity to cold and electricity, decreased width of the apical foramen, and mineralization within the canal space. CONCLUSIONS: Transplantation of allogeneic MSCs induces the formation of dental pulp-like tissue in permanent immature apex teeth with pulp necrosis and apical periodontitis. Implant of MSCs constitutes a potential therapy in regenerative endodontics in pediatric dentistry. Future studies incorporating a larger sample size may confirm these results.

Treatment outcomes of regenerative endodontic therapy in immature permanent teeth with pulpal necrosis: A systematic review and network meta-analysis.

AIM: The aim of this study was to assess which treatment modality regarding scaffold selection for immature permanent teeth with pulpal necrosis will be the most successful for regenerative endodontic treatment (RET). METHODOLOGY: PubMed, Cochrane, Web of Science and Embase, and additional records until August 2022 were searched providing a total of 3021 articles, and nine of these articles were included for quantitative synthesis. The reviewers selected eligible randomized controlled trials and extracted pertinent data. Network meta-analysis was conducted to estimate treatment effects for primary outcomes (clinical and radiographic healing) and secondary outcomes (apical closure, root length and root wall thickness increase) following RET [mean difference (MD); 95% credible interval (CrI) and surface under the cumulative ranking curve (SUCRA)]. The quality of the included studies was appraised by the revised Cochrane risk of bias tool, and the quality of evidence was assessed using the GRADE approach. RESULTS: Six interventions from nine included studies were identified: blood clot scaffold (BC), blood clot scaffold with basic fibroblast growth factor, blood clot scaffold with collagen, platelet pellet, platelet-rich plasma (PRP) and platelet-rich fibrin (PRF). The PRP scaffold showed the greatest increase in root lengthening at 6-12 months (MD = 4.2; 95% CrI, 1.2 to 6.8; SUCRA = 89.0%, very low confidence). PRP or PRF achieved the highest level of success for primary and secondary outcomes at 1-6 and 6-12 months. Blood clot scaffold (with collagen or combined with basic fibroblast growth factor (bFGF)) achieved the highest level of success for secondary outcomes beyond 12 months follow-up. A very low to low quality of evidence suggests that both PRP and PRF exhibit the greatest success evaluating primary and secondary outcomes within 12 months postoperatively compared to the traditional blood clot scaffold protocol. CONCLUSION: Limited evidence suggests both PRP and PRF exhibit success in the short-term, not long-term. The value of this information stems in its recommendation for future randomized trials prioritizing both of these materials in their protocol.

Pulp Regenerative Therapy Using Autologous Dental Pulp Stem Cells in a Mature Tooth with Apical Periodontitis: A Case Report.

The utility and feasibility of pulp regenerative therapy with autologous dental pulp stem cells (DPSCs) in mature teeth with irreversible pulpitis were clinically demonstrated. On the other hand, there is no evidence of the utility of DPSCs in mature teeth with apical periodontitis. The aim of this case report was to describe the potential utility of regenerative cell therapy in mature teeth with apical periodontitis. A 44-year-old man was referred for pulp regeneration due to a periapical lesion in his maxillary first premolar. Root canal disinfection was performed by irrigation and intracanal medication by nanobubbles with levofloxacin and amphotericin B in addition to conventional irrigation. Autologous DPSCs isolated from an extracted third molar were transplanted into the root canal after residual bacteria and fungi were below the detection level by polymerase chain reaction assay using universal genes to amplify specific regions within bacterial 16S ribosomal DNA and fungal ribosomal DNA (ITS1), respectively. There were no adverse events or systemic toxicity assessed for clinical evaluations during the 79-week-follow-up period and laboratory evaluations after 4 weeks. The affected tooth was responsive to the electric pulp test. Cone-beam computed tomographic imaging revealed a reduced lesion size, remission of the periapical tissue, and mineralized tissue formation in the apical part of the canal after 79 weeks. The signal intensity on magnetic resonance imaging of the regenerated tissue in the affected tooth was comparable to that of the normal pulp in the adjacent teeth after 24 weeks. This case report demonstrated the potential use of DPSCs for pulp regenerative therapy in mature teeth with apical periodontitis.

Evaluation of the efficacy of injectable platelet-rich fibrin versus platelet-rich plasma in the regeneration of traumatized necrotic immature maxillary anterior teeth: A randomized clinical trial.

BACKGROUND/AIM: This study aimed at comparing the regenerative potential of injectable platelet-rich fibrin (i-PRF) (Group 1) and platelet-rich plasma (Group 2) scaffolds. MATERIALS AND METHODS: Twenty-three patients, aged from 9 to 24 years, having 24 immature traumatized necrotic maxillary anterior teeth, were enrolled. Teeth trauma was confirmed by patients' history. Preoperative three-dimensional scans were done. In the first visit, canals were irrigated with 1.5% sodium hypochlorite then medicated with calcium hydroxide. After 2 weeks, patients were randomly assigned into one of the treatment groups (n = 12). The platelet concentrate was applied after centrifuging 10 mL of autologous venous blood with respect to the centrifugation protocol for each platelet concentrate. Patients were recalled at 6 and 12 months posttreatment, during which clinical and radiographic examinations and assessment of pulp sensitivity were done. Three-dimensional scanning was done after 12 months. The increase in root length and decrease in root canal diameters were calculated at three canal levels. Statistical analysis was done using the paired t-test and the independent t-test. The significance level was set at p < .05. RESULTS: There was no statistically significant difference between both groups regarding the increase in root length, decrease in coronal and middle canal diameters and the response to the electric pulp tester. Group (1) showed significantly greater decrease in apical canal diameter than Group (2) (p = .008). CONCLUSION: I-PRF can be considered as a valid regenerative scaffold for clinical use and with regards to the easier preparation technique, it is more recommended than platelet-rich plasma.

Cell-Based Regenerative Endodontics for the Treatment of Irreversible Pulpitis: AnIn VivoInvestigation.

INTRODUCTION: This study aims to investigate the ability of umbilical cord mesenchymal stem cells (UC-MSC) to enhance the regeneration of pulp-dentin complex in immature permanent teeth with irreversible pulpitis. METHODS: A total of 32 mandibular premolar teeth with immature apices in 5 dogs were used in this in-vivo randomized controlled trial (RCT). Eight healthy teeth without pre-existing pathosis served as the positive control samples and received no treatment, while in another 8 teeth, the pulp was completely extirpated (negative control). Class V cavities were prepared to induce inflammation in the remaining 16 teeth (groups 3 and 4) and the pulp was extirpated 2-4 mm short of the radiographic apex. Of the 16, the 8 teeth in group 4 received 1 mL of cord blood stem cells with a hydrogel scaffold. Blood clots were covered with mineral trioxide aggregates at the cementoenamel junction in the experimental groups, and teeth were filled with RMGI and composite. Three months later, block sections were removed for histologic evaluations for the evaluation of postoperative apical closure, degree of inflammation, and presence of normal pulp tissue. The data were statistically analyzed with the chi-square test (P < .05). RESULTS: All teeth with complete pulp extirpation demonstrated pulpal necrosis with no postoperative closure of their apices, while apical closure was seen in all the teeth in the remaining groups. There was a statistically significant (P < .001) difference in the presence of inflammation and normal pulp tissue between the experimental groups. The teeth in group 3 showed normal pulp tissue extending to the level of MTA, but there was inflammation within the canal space. In contrast, the teeth in the UC-MSC group demonstrated organized, normal pulp tissue with no inflammation. CONCLUSION: Based on these results, the regeneration of the pulp-dentin complex is possible with no inflammation when UC-MSCs are used and 2-4 mm of the apical pulp remains intact in immature teeth with irreversible pulpitis.

Indications for root canal treatment following traumatic dental injuries to permanent teeth.

The dental pulp may respond favourably or unfavourably to traumatic dental injuries. The most serious unfavourable responses are pulp necrosis and infection of the root canal system. These cause apical periodontitis and/or external inflammatory resorption of the tooth. The following injuries require root canal treatment as part of their emergency management-(A) complicated crown fractures (but some may be suitable for conservative pulp treatments, such as pulp capping, partial pulpotomy or pulpotomy), (B) complicated crown-root fractures, (C) supra-crestal coronal third root fractures and (D) injuries where pulp necrosis is predictable or highly likely to occur AND where there has been damage to the root surface and/or periodontal ligament with the aim of preventing external inflammatory resorption. This latter group of injuries are avulsion, intrusion, lateral luxation with a crown fracture, extrusion with a crown fracture (all in fully developed teeth) plus avulsion with a crown fracture and intrusion with a crown fracture (both in incompletely developed teeth). All other injuries should not have root canal treatment commenced as part of the emergency management, but they must be reviewed regularly to monitor the pulp for any adverse changes to its status, particularly pulp necrosis and infection of the root canal system.

Pulp regeneration: follow the guide / Régénération pulpaire : suivez le guide

Introduction: What if we changed our point of view? What if we approached endodontics from a biological perspective rather than a mechanistic one? What if, in the case of pulpal tissue necrosis, we were to consider an alternative to apexification therapies? Is pulp tissue regeneration now possible? Objective: Regenerative endodontic therapy (RET) aims to regenerate the pulp-dentin complex damaged by infection, trauma, or developmental anomaly of immature permanent teeth with necrotic pulp. The new intracanal tissue formation is expected to display pulp-like architecture and functions. There are two different based to tissue engineering approaches described to perform RET: cell-free CF-RET that attempt to induce host endogenous cells or stem cells to migrate into the root canal for regeneration or cell-based CB-RET which introduce exogenously prepared cells or stem cells into the canal for regeneration. Material and Method: CB-RET is the basis of current protocols recommended by the American Association of Endodontists (AAE) and the European Society of Endodontology (ESE) for the treatment of necrotic immature permanent teeth, with or without LIPOE. In this article, after defining the above-mentioned concepts, we will describe the ESE protocol and discuss the key steps for "getting started with endodontic regeneration". Conclusion: Each stage of the protocol must be carried out rigorously so as not to compromise the stages of the various biological processes involved. The practitioner has to stay informed of advances in knowledge resulting from research and new protocols to be published.

Introduction: Et si nous changions de point de vue ? Et si nous abordions l'endodontie d'un point de vue biologique et non mécanistique ? Et si, devant la nécrose du tissu pulpaire, nous envisagions une alternative aux thérapeutiques d'apexification ? La régénération du tissu pulpaire est-elle désormais possible ? Objectif: L'objectif des thérapeutiques régénératives endodontiques (regenerative endodontic therapy ou RET) est de récréer au sein du canal radiculaire un tissu semblable au complexe dentino-pulpaire tant sur le point de l'organisation cellulaire que sur le point fonctionnel. Deux concepts basés sur les principes de l'ingénierie tissulaire sont décrits : l'un basé sur la transplantation de cellules souches : le CB-RET (Cell-based RET) et l'autre basé sur le cell homing, c'est-à-dire sur le recrutement de cellules souches localisées à proximité de l'apex : le CF-RET (Cell-free RET). Matériel et méthode: Les protocoles actuels recommandés par l'Association Américaine des Endodontistes (American Association of Endodontists ou AAE) et la Société Européenne d'Endodontie (European Society of Endodontology ou ESE) dans le traitement des dents permanentes immatures nécrosées en présence ou non de lésion inflammatoire périapicale d'origine endodontique (LIPOE) sont basés sur le CF-RET. Dans cet article, après avoir défini les concepts cités précédemment, nous décrirons le protocole de l'ESE et discuterons des étapes clés pour « se mettre à la régénération endodontique ¼. Conclusion: Chaque étape du protocole doit être conduite avec rigueur afin de ne pas compromettre les étapes des différents processus biologiques engagés. Le praticien devra se tenir informé des avancées des connaissances issues des travaux de recherche et des nouveaux protocoles qui seront édités.

Implications of root, pulp chamber, and canal anatomy on pulpotomy and revitalization procedures.

OBJECTIVES: This review aims to discuss the implications of anatomy of the root, pulp chamber, and canals on pulpotomy and revitalization procedures (RPs) as treatment alternatives to root canal treatment procedures. METHODS: This narrative review was undertaken to address two main questions - why remove vital pulp tissue in teeth with complex canal anatomy when it can be preserved? And why replace the necrotic pulp in teeth with mature roots with a synthetic material when we can revitalize? This review also aims to discuss anatomical challenges with pulpotomy and revitalization procedures. RESULTS: Maintaining the vitality of the pulp via partial or full pulpotomy procedures avoids the multiple potential challenges faced by clinicians during root canal treatment. However, carrying out pulpotomy procedures requires a meticulous understanding of the pulp chamber anatomy, which varies from tooth to tooth. Literature shows an increased interest in the application of RPs in teeth with mature roots; however, to date, the relation between the complexity of the root canal system and outcomes of RPs in necrotic multi-rooted teeth with mature roots is unclear and requires further robust comparative research and long-term follow-up. CONCLUSIONS: Whenever indicated, pulpotomy procedures are viable treatment options for vital teeth with mature roots; however, comparative, adequately powered studies with long-term follow-up are needed as a priority in this area. RPs show promising outcomes for necrotic teeth with mature roots that warrant more evidence in different tooth types with long-term follow-ups.  CLINICAL RELEVANCE: Clinicians should be aware of the pulp chamber anatomy, which is subject to morphological changes by age or as a defensive mechanism against microbial irritation, before practicing partial and full pulpotomy procedures. RP is a promising treatment option for teeth with immature roots, but more evidence is needed for its applications in teeth with mature roots. A universal consensus and considerably more robust evidence are needed for the standardization of RPs in teeth with mature roots.

Treatment outcomes of regenerative endodontic procedures in nonvital mature permanent teeth: a retrospective study.

OBJECTIVES: This retrospective study was undertaken to clinically and radiographically evaluate the long-term outcomes of regenerative endodontic procedures (REPs) for nonvital mature permanent teeth, to analyze predictors influencing treatment outcomes. METHODS: Nonvital mature permanent teeth treated by REPs with a minimum follow-up period of 6 months were included from 2015 to 2017. Treatment outcomes were categorized as success and failure. The periapical status and lesion healing were assessed in terms of the periapical index (PAI) and the percentage changes in periapical radiolucency (PARL) area. The clinical and radiographic outcomes of REPs were assessed by Mann-Whitney test at different follow-up period. Kaplan-Meier curves and Univariate Cox regression analysis were conducted to assess the success and identify potential predictors affecting outcomes, respectively. RESULTS: A total of 37 mature teeth with an average follow-up of 4.3 years satisfied the criteria, and 89.2% of the teeth had a successful outcome. Significant differences in PAI scores were found between each period with respect to the baseline (p < .05). Among different periods, there was a significant difference between intervals of 3-6 months and 7-12 months (p = .039) and no significant difference between each interval of more than 12 months (p > .05). Eighty-seven percent of teeth with preoperative PARL presented completely healed. REPs significantly decreased the PARL area at the interval of 7-12 months compared to 3-6 months (p = .025), with no significant difference between each interval of more than 12 months (p > .05). No significant predictor was found for the success of outcome (p > .05). Thirteen teeth (35.1%) regained pulp sensibility, and 40.5% of the teeth exhibited intracanal calcification. CONCLUSIONS: Within the limitations of this study, REPs provided a high long-term success rate and promoted the resolution of PARL as a biologically-based alternative treatment option for nonvital mature teeth. CLINICAL RELEVANCE: REPs provide a high long-term success rate and promoted healing of apical periodontitis comparable with reported outcomes for root canal therapy of mature teeth.

Regenerative endodontic procedures: are they more successful in mature permanent teeth with necrotic pulp than in immature teeth?

DATA SOURCES: Five scientific databases were electronically searched: PubMed, EMBASE, OpenGrey, Web of Science and Cochrane Library.  The search was conducted until 17 February 2022 without any restriction on date of publication but was restricted to English language. Relevant studies were also screened for related publications. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of regenerative endodontic procedures (REPs) in mature and immature permanent teeth with necrotic pulp and to evaluate if the success rate was affected by the stage of root development. STUDY SELECTION: Types of studies: all of the included studies were randomised controlled trials (RCTs). TYPES OF PARTICIPANTS: people with necrotic permanent teeth (immature or mature) treated with regenerative endodontic procedures. Types of interventions: regenerative endodontic procedures. Language: RCTs published in English. EXCLUSION CRITERIA: Types of studies: (1) case reports, (2) retrospective cohort trials, (3) prospective cohort trials, (4) animal trials, (5) in-vitro trials, (6) non-randomised trials. POPULATION: primary teeth. Types of interventions: no details about the clinical procedures. Follow-up period: <6 months. DATA EXTRACTION AND SYNTHESIS: The titles and abstracts of the RCTs identified by the search strategies were independently screened by two reviewers. After the initial screening, the full text of the relevant trials were reassessed against the inclusion and exclusion criteria. Discrepancies and disagreements were resolved by consensus after including a third reviewer. RESULTS: Following the initial electronic and manual searches, a total of 3766 articles were initially identified. This was reduced to 2739 articles after duplicates were removed. However, after the initial screening phase, 35 articles were considered potentially relevant and qualified for full-text scrutiny. Out of the 35 articles, only 27 were considered eligible for inclusion. The differences in the success rate and the asymptomatic rate between the mature and immature permanent teeth with necrotic pulp were not statistically significant. However, the differences between the two groups were statistically significant in the rate of positive response to electrical pulp testing. CONCLUSIONS: Based on the results of this systematic review and meta-analysis, the authors concluded that REPs are an effective therapy and can achieve high success rates for both mature and immature necrotic permanent teeth. It was also concluded that the REPs were more successful in regaining vitality responses for mature compared with immature permanent teeth with necrotic pulps.

Reparative Dentin Formation Following Dental Pulp Capping is Mediated by TNFR1 In Vivo.

INTRODUCTION: Tumor necrosis factor (TNF)-α is a pro-inflammatory cytokine that promotes biomineralization in vitro in dental pulp cells. However, the role of TNF-α-TNF receptor 1 (TNFR1) signaling in reparative dentin formation and related inflammatory pathways is not known. Therefore, the aim of this study was to evaluate the role of the TNF-α-TNFR1 axis in dental pulp repair following pulp capping in vivo. METHODS: Dental pulp repair response of genetically deficient TNF-α receptor-1 mice (TNFR1-/-; n = 20) was compared with that of C57Bl6 mice (wild type [WT]; n = 20). Pulp capping was performed with mineral trioxide aggregate on the mandibular first molars of mice. After 7 and 70 days, tissues were collected and stained with hematoxylin and eosin for histopathological and histometric evaluation, and assessed by the Brown and Brenn methods for histomicrobiological analysis and by immunohistochemistry to localize TNF-α, Runt-related transcription factor 2, Dentin Sialoprotein (DSP) and Osteopontin (OPN) expression. RESULTS: Compared with WT mice, TNFR1-/- mice showed significantly decreased reparative dentin formation with a lower mineralized tissue area (P < .0001). Unlike WT mice, TNFR1-/- mice also exhibited significant dental pulp necrosis, neutrophil recruitment, and apical periodontitis formation (P < .0001) without bacterial tissue invasion. TNFR1-/- animals further exhibited decreased TNF-α, DSP, and OPN expression (P < .0001), whereas Runt-related transcription factor 2 expression was unchanged (P > .05). CONCLUSION: The TNF-α-TNFR1 axis is involved in reparative dentin formation following dental pulp capping in vivo. Genetic ablation of TNFR1 modified the inflammatory process and inhibited the expression of the DSP and OPN mineralization proteins, which culminated in dental pulp necrosis and development of apical periodontitis.

Current Management of Dens Evaginatus Teeth Based on Pulpal Diagnosis.

INTRODUCTION: Dens evaginatus (DE) is a dental anomaly with a supernumerary tubercle projection that typically contains dentin and pulp tissue. However, the tubercle projection can fracture, exposing the dentin and potentially the dental pulp, which induces pulpal diseases. Managing DE should be primarily based on the clinical diagnosis of the pulp. METHODS: The literature search in prevalence, prophylaxis, and management of dens evaginatus was performed in PubMed database as well as by manual search, in which the related contents were collected and descriptively analyzed. RESULTS: Of the 264 searched literatures, 62 articles were included for this scoping review. The prophylactic management of the tubercle of DE teeth with a normal pulp should be performed as early as possible by the prep-and-fill technique or the reinforcement technique to preserve tooth vitality and continued root development, with the former reported to be superior compared with the latter. Furthermore, DE teeth with reversible pulpitis should be managed with the prep-and-fill technique. For DE teeth with irreversible pulpitis, vital pulp therapy, ie, partial or full/coronal pulpotomy, should be considered when the pulpal inflammation is limited to the coronal pulp to preserve the vitality of the radicular pulp that induces apexogenesis. A pulpectomy should be performed if the pulpal inflammation has progressed into the radicular pulp. For DE teeth with pulpal necrosis (or after pulpectomy) and immature roots, mineral trioxide aggregate apexification or regenerative endodontic procedures are the treatment options. For DE teeth with pulpal necrosis and complete root formation, nonsurgical root canal treatment is the treatment of choice. A flow chart of the decision-making for managing DE teeth based on pulpal diagnosis is proposed. CONCLUSION: DE teeth should be properly managed, by prophylaxis or treatment, depending on pulpal diagnosis and related factors.

Long-term follow-up of single-visit pulp revascularisation for the dens evaginatus and dens invaginatus: Cases report.

This article documents cases of single-visit pulp revascularisation for dens evaginatus and dens invaginatus, without using intracranial medicaments or antibiotics, aiming to provide a potentially applicable protocol for pulp revascularisation procedure in a single-visit. Two patients with chief complaints of pain and swelling visited a dental hospital. Radiographs revealed that the causative teeth had an open apex and periapical radiolucency, and the teeth were diagnosed as pulp necrosis and acute apical abscess or symptomatic apical periodontitis. For both cases, single-visit revascularisation was completed without intracanal medicaments or antibiotics. The patients were periodically recalled to evaluate periapical healing after treatment. The apical lesion healed, and the root dentin thickening was observed. The single-visit pulp revascularisation procedure without using specific intracanal medicaments can produce clinically favourable results for these dental anomalies.

Histologic and Electron Microscopic Characterization of a Human Immature Permanent Premolar with Chronic Apical Abscess 16 Years after Regenerative Endodontic Procedures.

Previous studies have reported successful clinical outcomes after regenerative endodontic procedures (REPs) for immature permanent teeth with pulpal infection. However, it remains unclear whether the procedures promote true regeneration or repair. This case report describes the histologic and electron microscopic characteristics of a human immature permanent premolar with a chronic apical abscess that was treated with an REP. Tooth #20 of a 9-year-old girl underwent an REP. At the 6-year follow-up, the patient was asymptomatic, and closure of the apex and thickening of the dentinal walls were observed. However, 16 years after the procedure, apical periodontitis recurred, necessitating apical surgery. The resected root fragments were obtained during the surgery and analyzed using micro-computed tomography, light microscopy, and scanning electron microscopy. Distinct dentinal tubules and interglobular dentin were observed in the regenerated hard tissue. Cementum-like tissue and a root canal were also observed in the apical fragment. The regenerated root tissue in this case exhibited a structure similar to the native root structure. Therefore, we believe that cell-free REPs possess regenerative potential for teeth diagnosed with pulp necrosis and chronic apical abscess.

Is Etiology a Key Factor for Regenerative Endodontic Treatment Outcomes?

INTRODUCTION: This study aimed to evaluate treatment outcomes of regenerative endodontic treatment (RET) in nonvital immature permanent teeth due to developmental malformation and trauma, and to analyze the influence of etiology on the prognosis. METHODS: Fifty-five cases were included and divided into a malformation group (n = 33) and a trauma group (n = 22). Treatment outcomes were classified as healed, healing, and failure. Root development was evaluated in terms of root morphology and the percentage changes in root length, root width, and apical diameter during a follow-up period of 12-85 months (mean 30.8 months). RESULTS: The mean age and the mean degree of root development in the trauma group were significantly younger than that in the malformation group. The success rate of RET was 93.9% (81.8% healed, 12.1% healing) in the malformation group and 90.9% (68.2% healed, 22.7% healing) in the trauma group, showing no statistically significant difference. The proportion of type I-III root morphology in the malformation group (97%, 32/33) was significantly higher than that in the trauma group (77.3%, 17/22) (P < .05), whereas there was no significant difference in the percentage changes of root length, root width, and apical diameter between the 2 groups. Six cases (6/55, 10.9%) showed no significant root development (type IV-V) (1 in the malformation group and 5 in the trauma group). Six cases (6/55, 10.9%) revealed intracanal calcification. CONCLUSIONS: RET achieved reliable outcomes regarding the healing of apical periodontitis and continued root development. The etiology seems to influence the outcome of RET. Malformation cases presented with a better prognosis than trauma cases after RET.