Exosomes as Promising Therapeutic Tools for Regenerative Endodontic Therapy.

Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.

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.

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.

Dental Pulp Cell Transplantation Combined with Regenerative Endodontic Procedures Promotes Dentin Matrix Formation in Mature Mouse Molars.

Regenerative endodontic procedures (REPs) are promising for dental pulp tissue regeneration; however, their application in permanent teeth remains challenging. We assessed the potential combination of an REP and local dental pulp cell (DPC) transplantation in the mature molars of C57BL/6 mice with (REP + DPC group) or without (REP group) transplantation of DPCs from green fluorescent protein (GFP) transgenic mice. After 4 weeks, the regenerated tissue was evaluated by micro-computed tomography and histological analyses to detect odontoblasts, vasculogenesis, and neurogenesis. DPCs were assessed for mesenchymal and pluripotency markers. Four weeks after the REP, the molars showed no signs of periapical lesions, and both the REP and REP + DPC groups exhibited a pulp-like tissue composed of a cellular matrix with vessels surrounded by an eosin-stained acellular matrix that resembled hard tissue. However, the REP + DPC group had a broader cellular matrix and uniquely contained odontoblast-like cells co-expressing GFP. Vasculogenesis and neurogenesis were detected in both groups, with the former being more prominent in the REP + DPC group. Overall, the REP was achieved in mature mouse molars and DPC transplantation improved the outcomes by inducing the formation of odontoblast-like cells and greater vasculogenesis.

Final irrigation with bioglass solution in regenerative endodontic procedure induces tissue formation inside the root canals, collagen maturation, proliferation cell and presence of osteocalcin.

AIM: To evaluate the influence of an experimental solution of cobalt-doped F18 bioactive glass (F18Co) on tissue repair following regenerative endodontic procedure (REP) in rat molars. METHODOLOGY: The F18Co solution was prepared at a ratio of 1:5 F18Co powder to distilled water. The right or left upper first molars of 12 Wistar rats were used, where the pulps were exposed, removed, and irrigated with 2.5% sodium hypochlorite (NaOCl), followed by 17% ethylenediaminetetraacetic acid (EDTA) (5 min each). Subsequently, the molars were divided into two groups (n = 6): REP-SS and REP-F18Co, where they received a final irrigation (5 min) with saline solution (SS) or F18Co solution, respectively. Then, intracanal bleeding was induced, and the tooth was sealed. Untreated molars were used as controls (n = 3). At 21 days, the rats were euthanized, and the specimens were processed for analysis of mineralized tissue and soft tissue formation inside the root canal using haematoxylin-eosin. The presence and maturation of collagen were evaluated by Masson's trichrome and picrosirius red staining. Immunolabelling analyses of proliferating cell nuclear antigen (PCNA) and osteocalcin (OCN) were performed. The data were submitted to the Mann-Whitney U-test (p < .05). RESULTS: There was a similar formation of mineralized tissue in thickness and length in REP-SS and REP-F18Co groups (p > .05). Regarding the presence of newly formed soft tissue, most specimens of the REP-F18Co had tissue formation up to the cervical third of the canal, whilst the REP-SS specimens showed formation up to the middle third (p < .05), and there was higher maturation of collagen in REP-F18Co (p < .05). The number of PCNA-positive cells found in the apical third of the root canal was significantly higher in the F18Co group, as well as the OCN immunolabelling, which was severe in most specimens of REP-F18Co, and low in most specimens of REP-SS. CONCLUSION: The final irrigation with F18Co bioactive glass solution in REP did not influence mineralized tissue formation but induced soft tissue formation inside the root canals, with higher collagen maturation, and an increase in PCNA-positive cells and OCN immunolabelling.

Comparison of the removal of intracanal medicaments used in regenerative endodontics from root canal system using needle, ultrasonic, sonic, and laser-activated irrigation systems.

This study aimed to compare the syringe-needle irrigation (SNI), passive ultrasonic irrigation (PUI), EDDY, and shock wave-enhanced emission photoacoustic streaming (SWEEPS) techniques regarding calcium hydroxide and double antibiotic paste removal from the root canal in regenerative endodontic treatments. Eighty single-rooted human teeth were decoronated and enlarged up to #100 to stimulate the immature tooth model. Root canals were irrigated with 1.5% sodium hypochlorite followed by saline solution according to the regenerative endodontic treatment protocol. Dressed teeth were divided into 2 main groups regarding the used intracanal medicaments. Calcium hydroxide and double antibiotic paste were introduced to the canals, and teeth were stored for 3 weeks. Each medicament group was divided into 4 subgroups according to the activation techniques. Medicaments were removed using a 17% EDTA solution. Teeth were split longitudinally into two parts. The remaining medicaments were evaluated under a stereo microscope with a scoring system. Data were analyzed with the Kruskal-Wallis and Mann-Whitney U tests. Regardless of the used irrigation activation systems, there was no statistically significant difference between the removal of the CH and DAP from the root canal (P>0.05). While SWEEPS had the highest ability regarding the removal of intracanal medicaments, syringe-needle irrigation had the lowest (P<0.05). There was no statistically significant difference between PUI and EDDY (P>0.05). Complete removal of intracanal medicaments could not be achieved with any techniques. SWEEPS technology was more effective in removing intracanal medicaments in regenerative endodontic treatments compared to the sonic and ultrasonic irrigation activation systems.

In vitro and in vivo evaluation of iRoot BP Plus as a coronal sealing material for regenerative endodontic procedures.

OBJECTIVES: To investigate in vitro effects of a nanoparticle bioceramic material, iRoot BP Plus, on stem cells from apical papilla (SCAP) and in vivo capacity to induce pulp-dentin complex formation. MATERIALS AND METHODS: The sealing ability of iRoot BP Plus was measured via scanning electron microscopy (SEM). SCAP were isolated and treated in vitro by iRoot BP Plus conditioned medium, with mineral trioxide aggregate (MTA) conditioned medium and regular medium used as controls, respectively. Cell proliferation was assessed by BrdU labeling and MTT assay and cell migration was evaluated with wound healing and transwell assays. Osteo/odontogenic potential was evaluated by Alizarin red S staining and qPCR. Pulp-dentin complex formation in vivo was assessed by a tooth slice subcutaneous implantation model. RESULTS: iRoot BP Plus was more tightly bonded with the dentin. There was no difference in SCAP proliferation between iRoot BP Plus and control groups (P > 0.05). iRoot BP Plus had a greater capacity to elevated cell migration (P < 0.05) and osteo/odontogenic marker expression and mineralization nodule formation of SCAP compared with MTA groups (P < 0.05). Furthermore, the new continuous dentine layer and pulp-like tissue was observed in the iRoot BP Plus group in vivo. CONCLUSIONS: iRoot BP Plus showed excellent sealing ability, promoted the migration and osteo/odontogenesis of SCAP and induced pulp-dentin complex formation without affecting the cell proliferation, which indicated iRoot BP Plus was a promising coronal sealing material in REPs. CLINICAL RELEVANCE: The coronal sealing materials play crucial roles for the outcomes of REPs. This study showed that iRoot BP Plus has good coronal sealing and promote pulp-dentin complex formation compared with MTA, providing experimental evidences for the clinical application of iRoot BP Plus as a promising coronal seal material in REPs.

Effect of EDTA Activation on Blood Clot Structure in Regenerative Endodontics: A Scanning Electron Microscopy Study.

INTRODUCTION: EDTA plays a crucial role in regenerative endodontic therapy (RET) because of its significant biological effects. However, EDTA is also recognized as the preferred anticoagulant for hematologic tests. Thus, this study aimed to assess the influence of different EDTA activation techniques on the morphology of blood clots after conditioning the root canal dentin. METHODS: Forty extracted human teeth were prepared to simulate immature teeth and divided into the following 5 groups: (1) saline solution (negative control), (2) EDTA 17% + saline solution (CNI), (3) CNI + ultrasonic activation, (4) CNI + Easy clean activation, and (5) CNI + XP-endo Finisher activation. After irrigation, the roots were cleaved, and the root canals were filled with human blood to clot formation. The morphology and density of erythrocytes, platelets, and the fibrin network were observed using a scanning electron microscope. The fibrin network density was classified using a 4-point scale. Data were analyzed using the Friedman test and the Kruskal-Wallis test with Bonferroni adjustment (α = 5%). RESULTS: All groups exhibited consistent blood clot morphology characterized by a high density of erythrocytes, platelets, and white blood cells throughout the entire length of the root canal. The negative control group showed statistically significant high scores of fibrin density compared with the CNI group in all root thirds (P < .05). However, there was no statistical difference in the scores for the fibrin network density between the groups irrigated with EDTA with and without activation (P > .05). CONCLUSIONS: EDTA may impair the fibrin network formation compared with the saline group. However, EDTA activation did not significantly change the effects on the blood clot in contact with the conditioned intraradicular dentin.

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.

Citric Acid Conditioning as an Alternative to EDTA for Growth Factors Release and Stem Cell Response in Regenerative Endodontics: A Systematic Review of In Vitro Studies.

INTRODUCTION: Citric acid (CA) conditioning may be a promising alternative to ethylenediaminetetraacetic acid (EDTA) in regenerative endodontic procedures, as reported to improve growth factors' release from dentin. This review systematically investigated the effect of CA conditioning on the growth factors release from dentin and cell behavior compared to EDTA conditioning. METHODS: Searches were conducted (PubMed/MEDLINE, Scopus, Web of Science, Embase, SciELO, Cochrane Library, and grey literature) until May-2023. Only in vitro studies that evaluated the effects of CA on growth factors' release from dentin and cell behavior outcomes compared to EDTA were included. The studies were critically appraised using a modified Joanna Briggs Institute's checklist. Meta-analysis was unfeasible. RESULTS: Out of the 335 articles screened, nine were included. Among these, three studies used dentin discs/roots from permanent human teeth; the rest combined them with stem cells. 10% CA for 5 or 10 minute was the most used protocol. Meanwhile, EDTA concentrations ranged from 10% to 17%. In eight studies examining the release of growth factors, five reported a significant release of transforming growth factor-ß after dentin conditioning with 10% CA compared to 17% EDTA. Regarding cell behavior (6 studies), three studies assessed cell viability. The findings revealed that 10% CA conditioning showed cell viability similar to those of 17% EDTA. Additionally, in two out of three studies, it was observed that 10% CA conditioning did not affect cell morphology. The studies had a low risk of bias. CONCLUSIONS: The use of 10% CA to condition dentin for 5-10 minutes resulted in a notable transforming growth factor -ß1 release, but its cell responses were similar to those of EDTA.

Effect of photobiomodulation therapy on TGF-ß release from dentin, migration and viability of dental pulp stem cells in regenerative endodontics treatment: An ex vivo study.

BACKGROUND AND AIM: Regenerative endodontic procedures (REPs) are oriented by the principles of tissue engineering, incorporating dental pulp stem cells (DPSC), crucial growth factors like Transforming growth factor-ß (TGF-ß1), and scaffolds to facilitate the regeneration of dental pulp tissues. The present study aimed to investigate the effect of photobiomodulation (PBM) therapy, using an 808 nm diode laser on cellular modulation mechanisms in REPs. METHOD AND MATERIAL: A total of 108 human dentin discs obtained from intact single root teeth were randomly assigned into six groups (n = 8): 1. Positive control (EDTA), 2. PBM-1 (3 J/cm2), 3. PBM-2 (5 J/cm2), 4. EDTA+PBM-1, 5. EDTA+PBM-2, and 6. Negative control (NaOCl). Then, an extract solution was prepared from each disc and the concentration of released TGF-ß1 from the discs was measured using enzyme-linked immunosorbent assay (ELISA). Moreover, the extract solution was added to DPSC culture medium to evaluate cell viability and migration through MTT assay and scratch test, respectively. RESULT: The group exposed to PBM-1 showed the highest cell viability, while treatment with EDTA and EDTA+PBM-2 decreased cellular viability. Also, the PBM-treated groups showed significantly higher release of TGF-ß1 compared to the negative control. EDTA and EDTA+PBM-1 showed the highest release among all the groups. No significant difference was found between EDTA and EDTA+PBM-1, as well as between PBM-1 and PBM-2. Moreover, the PBM-1 group exhibited the highest migration after 24 h, which was significantly greater than other groups, except for the PBM-2 group. CONCLUSION: According to the obtained data, 808 nm mediated-PBM (3 J/cm2), both independently and in conjunction with EDTA, enhanced the release of TGF-ß1 from dentin and improved cell viability and migration of DPSCs. It seems that, PBM under the specific parameters employed in this study, could be an effective adjunctive therapy in REPs.

Current Trends in Regenerative Endodontics: A Web-based Survey.

INTRODUCTION: The aim of this study was to ascertain the current trends in regenerative endodontic procedures (REPs) among clinicians, including case selection criteria and clinical protocols. METHODS: An online questionnaire consisting of provider demographics, case selection criteria for REPs, and clinical protocols was made available to members of the American Association of Endodontists and members of the Endolit website. Data were analyzed using the Fisher exact test. RESULTS: Two hundred seventy-two responses were analyzed (64.6% were men and 34.7% were women). Of those, 44.5% of respondents practiced in the United States, and 55.5% practiced outside of the Unites States. Most respondents (85.4%) reported performing REPs in their practice, and 92.2% were using sodium hypochlorite as one of their disinfecting irrigants. Calcium hydroxide was the most commonly used intracanal medicament (68.4%), and the majority of respondents use a blood clot alone as the scaffold (73.5%). Most (93%) of the providers reported using a bioceramic material for coronal capping. Practitioners outside the United States were found to be more likely to use adjunctive irrigation activation (P = .003). Younger practitioners preferred REPs over apexification (P = .01). Practitioners outside the United States were more likely to perform an REP in 1 visit (P = .006). Men were found to be more likely to always instrument the canal walls (P = .031). Women were found to be more likely to use manual irrigant activation, whereas men were more likely to use sonic activation (P = .043). CONCLUSIONS: There is significant heterogeneity within REPs regarding case selection and clinical protocol. Notable differences were observed from the reported findings of REPs from 5 years ago.

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.

The capability of regenerative endodontics to promote the complete root formation in immature permanent teeth with different initial pre-operative conditions.

OBJECTIVES: To describe the potential possibility of complete root formation after regenerative endodontic procedures (REPs) in immature permanent teeth with different initial pre-operative conditions. MATERIALS AND METHODS: Children who underwent REPs in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China, from January 2013 to December 2022 were enrolled. Whether the tooth achieved complete root formation was determined using post-operative periapical radiography. The potential possibility of complete root formation after REPs in immature permanent teeth with different initial conditions is discussed. RESULTS: A total of 428 teeth from 401 patients were included, of which 258 (60.2%) achieved complete root formation. In cases that achieved complete root formation, the most serious type of trauma was avulsion, the teeth with the worst initial root development were less than one-third of the development (stages 6-7), and the longest duration of the presence of apical lesions in the tooth before the first visit was more than 180 days. There is a significant difference in the root formation of teeth with different initial developmental stages and diagnoses. CONCLUSIONS: The active period of continued root formation was 5-21 months post-operatively. The higher the initial stage of root development and the shorter the duration of the presence of apical lesions in the tooth before the first visit, the greater the possibility of root formation. However, complete root formation may still be expected after REPs in severely injured immature permanent teeth and teeth with poor initial pre-operative root development conditions (less than stage 7) at the first visit. This is also true for teeth with long-term and large-scale apical lesions.

3D finite element analysis of stress distribution as a result of oblique and horizontal forces after regenerative endodontic treatment part II: comparison of material thickness.

AIM: This study aimed to evaluate the stress distribution caused by secondary trauma forces after regenerative endodontic treatment (RET) using different thicknesses of coronary barrier material with three-dimensional finite element analysis(FEA). METHOD: A control model was created using the tomography image of the immature maxillary central tooth with computer software.Study models were created with the modulus of elasticity and Poisson's ratio of the materials used in RET.Enamel, dentin, cementum, periodontal ligament, cortical, and cancellous bone were modeled. Coronary barrier materials were applied in 3 mm and 5 mm thicknesses (Model 1: control model, model 2:3 mm/Calcium Enriched Mixture(CEM), model 3:3 mm/Mineral Trioxide Aggregate(MTA), model 4:3 mm/Biodentin, model 5:5 mm/CEM, model 6:5 mm/MTA, model 7:5 mm/Biodentin). For the trauma force simulation, 300 N force in the horizontal direction was applied to the buccal surface of the tooth in the first scenario. For the second scenario, maximum bite force simulation, a force of 240 N in the oblique direction was applied to the palatal surface of the tooth. FEA was performed with Algor Fempro. The resulting stresses were recorded as Von Mises, maximum, and minimum principal stresses. RESULTS: Lower stress values were obtained in 5 mm models compared to 3 mm models. However, the difference between them was insignificant. Lower stress values were obtained in all RET models compared to the control model. The lowest stress values in dental tissues and bone tissue were obtained in the CEM models. CONCLUSION: This is the first study in which the stress caused by different thicknesses of CEM on dental tissues was evaluated with FEA. RET strengthens immature teeth biomechanically. CEM and Biodentin are more successful materials in stress distribution than MTA. Considering the cost of treatment, 3 mm material thickness is ideal for RET since there is no significant difference between the stress values resulting from the use of 5 mm and 3 mm coronary barrier material.

Analysis of the achievement of primary and secondary goals and influencing factors in single-rooted immature permanent teeth after regenerative endodontic procedures: a retrospective study.

OBJECTIVE: This study explored the achievement of primary and secondary goals and factors influencing their achievement in regenerative endodontic procedures (REPs) for immature permanent teeth. METHODS: Dental records of all patients who received REPs for immature permanent teeth at the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology between January 2012 and January 2023 were retrieved. The evaluation of the primary goal was based on medical and radiographic records. The achievement of the primary goal was defined as the absence of clinical signs and symptoms, such as pain, swelling, or sinus tract and the absence of periapical radiolucency, as assessed on postoperative periapical radiographs. The achievement of secondary goal represented increased root wall thickness and/or increased root length, that is, continued root development. Periapical radiographs before and after treatment were used to evaluate the achievement of the secondary goal. The secondary goal was required to be achieved alongside the achievement of primary goal. RESULTS: A total of 436 teeth (136 anterior and 300 posterior teeth) were included in this study, 96.1% of which demonstrated achievement of the primary goal. Signs of failure (17 teeth) included crown fracture and uncontrolled and recurrent periapical lesions. In addition, 77.8% of teeth demonstrated achievement of the secondary goal, and more than half of the teeth exhibited a complete root development. Evaluation factors included patients' age, sex, tooth type, etiology, preoperative periapical lesion, duration of clinical signs and symptoms, follow-up period, and stage of root development. The achievement of the primary and secondary goals were significantly related to age and tooth type (p < 0.05). CONCLUSIONS: Children with a younger initial visit age are more likely to achieve primary and secondary goals. Additionally, posterior teeth had an advantage over anterior teeth in achieving primary and secondary goals.

Short fiber reinforced composite on fracture strength of immature permanent anterior teeth with simulated regenerative endodontic procedures: an in vitro study.

The aim of the present study was to evaluate the effect of short fiber reinforced composite on the fracture strength of anterior immature teeth treated with regenerative endodontic procedures. A total of 120 permanent maxillary central incisors were selected, and root lengths were standardized. Except for the positive control group (n = 20), the root canals were instrumented to simulate immature teeth with incomplete root development, and the regenerative endodontic procedure was performed. Twenty instrumented teeth acted as negative controls (n = 20), and the remaining 80 teeth were randomly divided into 4 groups according to the chosen coronal restoration material: bulk fill, short fiber reinforced composite (SFRC), polyethylene fiber (Ribbond Ultra), and flowable composite resin. Each specimen was then subjected to fracture testing using a universal testing machine (AGS-X, Shimadzu, Japan). The load to fracture was recorded. Data were subjected to statistical analysis using analysis of variance and the Tukey Honestly Significant Difference test. A significant difference was detected between the groups (p < 0.05), with the positive control group showing the highest mean fracture strength. The SFRC group had significantly higher values than the bulk fill, polyethylene fiber, flowable composite resin and negative control groups. In conclusion, SFRC has a relatively high fracture strength compared to other materials used in regenerative endodontic procedures. The use of SFRC enhanced the fracture strength of immature permanent teeth.

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.