Investigation of the early apical release from endodontic hydrogels: A 3D printed model.

AIM: Regenerative Endodontic Procedures (REPs) using new materials such as hydrogels aim to replace current endodontic treatments, but numerous limitations are to overcome. Apical release was little explored in previous studies, especially regarding hydrogels that incorporate molecules, such as growth factors and antibiotics. Apical release is a key mechanism in achieving regeneration, as it could regulate disinfection or cell colonization. Few models exist for apical release, limiting the transfer of these devices from bench to bedside. This study aims to design a simple and standardized model to identify parameters that influence the early apical release kinetic of molecules from endodontic hydrogels. METHODOLOGY: Endodontic Release Inserts (ERI) were designed to mimic the situation of an immature incisor using three different diameters (Ø 0.5 to 2 mm) and to allow the study of the early release from a hydrogel in a 96-well plate. ERI was produced with a 3D printing machine. The kinetic release was investigated using 2 fluorescent, hydrophobic (BDP-500) and hydrophilic (Fluorescein) molecules, in different hydrogels (fibrin and agarose) and in various media (PBS or serum). The release kinetics were estimated by measuring the fluorescence at different time points (1 to 24 h). RESULTS: ERI use made it possible to report that apical diameters increase from 500 to 1000 µm was associated with an increase in release from 4.02 ± 1.63% to 11.53 ± 2.38% over 24 h. It also allowed us to report that bottom solution composition change from PBS to human serum was associated with an increase in the release of fatty acid molecules, whilst a decrease in the hydrogel concentration was associated with a variation in release kinetics. Moreover, nano-encapsulation of a molecule was associated with a decreased release over the first 24 h from 5.25 to 0%. CONCLUSION: ERI use enables investigation of the parameters influencing release kinetics from endodontic hydrogels. Further investigations are necessary to evaluate the interaction of these parameters with each other, in animal models and clinic.

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.

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.

An innovative cell-based transplantation therapy for an immature permanent tooth in an adult: a case report.

BACKGROUND: Immature teeth with necrotic pulps present multiple challenges to clinicians. In such cases, regenerative endodontic procedures (REPs) may be a favorable strategy. Cells, biomaterial scaffolds, and signaling molecules are three key elements of REPs. Autologous human dental pulp cells (hDPCs) play an important role in pulp regeneration. In addition, autologous platelet concentrates (APCs) have recently been demonstrated as effective biomaterial scaffolds in regenerative dentistry, whereas the latest generation of APCs-concentrated growth factor (CGF), especially liquid phase CGF (LPCGF)-has rarely been reported in REPs. CASE PRESENTATION: A 31-year-old woman presented to our clinic with the chief complaint of occlusion discomfort in the left mandibular posterior region for the past 5 years. Tooth #35 showed no pulp vitality and had a periodontal lesion, and radiographic examination revealed that the tooth exhibited extensive periapical radiolucency with an immature apex and thin dentin walls. REP was implemented via transplantation of autologous hDPCs with the aid of LPCGF. The periodontal lesion was managed with simultaneous periodontal surgery. After the treatment, the tooth was free of any clinical symptoms and showed positive results in thermal and electric pulp tests at 6- and 12-month follow-ups. At 12-month follow-up, radiographic evidence and three-dimensional models, which were reconstructed using Mimics software based on cone-beam computed tomography, synergistically confirmed bone augmentation and continued root development, indicating complete disappearance of the periapical radiolucency, slight lengthening of the root, evident thickening of the canal walls, and closure of the apex. CONCLUSION: hDPCs combined with LPCGF represents an innovative and effective strategy for cell-based regenerative endodontics.

Influence of extracellular matrix scaffolds on histological outcomes of regenerative endodontics in experimental animal models: a systematic review.

BACKGROUND: Decellularized extracellular matrix (dECM) from several tissue sources has been proposed as a promising alternative to conventional scaffolds used in regenerative endodontic procedures (REPs). This systematic review aimed to evaluate the histological outcomes of studies utilizing dECM-derived scaffolds for REPs and to analyse the contributing factors that might influence the nature of regenerated tissues. METHODS: The PRISMA 2020 guidelines were used. A search of articles published until April 2024 was conducted in Google Scholar, Scopus, PubMed and Web of Science databases. Additional records were manually searched in major endodontic journals. Original articles including histological results of dECM in REPs and in-vivo studies were included while reviews, in-vitro studies and clinical trials were excluded. The quality assessment of the included studies was analysed using the ARRIVE guidelines. Risk of Bias assessment was done using the (SYRCLE) risk of bias tool. RESULTS: Out of the 387 studies obtained, 17 studies were included for analysis. In most studies, when used as scaffolds with or without exogenous cells, dECM showed the potential to enhance angiogenesis, dentinogenesis and to regenerate pulp-like and dentin-like tissues. However, the included studies showed heterogeneity of decellularization methods, animal models, scaffold source, form and delivery, as well as high risk of bias and average quality of evidence. DISCUSSION: Decellularized ECM-derived scaffolds could offer a potential off-the-shelf scaffold for dentin-pulp regeneration in REPs. However, due to the methodological heterogeneity and the average quality of the studies included in this review, the overall effectiveness of decellularized ECM-derived scaffolds is still unclear. More standardized preclinical research is needed as well as well-constructed clinical trials to prove the efficacy of these scaffolds for clinical translation. OTHER: The protocol was registered in PROSPERO database #CRD42023433026. This review was funded by the Science, Technology and Innovation Funding Authority (STDF) under grant number (44426).

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.

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).

Impact of using XP-endo finisher and nanobubble water during EDTA dentin conditioning on TGF-ß1 release in regenerative endodontic procedures.

INTRODUCTION: Transforming Growth Factor-Beta 1 (TGF-ß1) plays a crucial role in the success of Regenerative Endodontic Procedures (REPs) as they directly impact the proliferation and differentiation of stem cells. TGF-ß1 is released by conditioning of the dentin matrix using 17% EDTA. EDTA was found to have deleterious effects on dentin especially in immature teeth with fragile dentin walls. Decreasing the irrigation time was reported to decrease these effects. Accordingly, enhancement and activation of the EDTA solution to maintain its efficiency in TGF-ß1 release from dentin and thus compensating the reduction in irrigation time was employed. EDTA solution was enhanced by adding Nanobubble (NB) water which contains oxygen filled cavities less than 200 nm in diameter. Additionally, EDTA was activated with XP-endo Finisher rotary file. The aim of this study was to assess the impact of NB enhancement and/or XP-endo Finisher activation of the EDTA solution on the TGF-ß1 release from dentin. METHODS: Fifty standardized root segments with open apex were allocated to two main groups according to whether EDTA was enhanced with NB water or not, and within each group whether XP-endo Finisher activation was used or not in addition to a Negative Control group. The concentration of the released TGF-ß1 in the root canal was measured using enzyme-linked immunosorbent assay (ELISA). The statistical analysis was done using the Shapiro- Wilk, Kolmogorov Smirnov, ANOVA and Post-hoc Tukey tests. RESULTS: All groups released a considerable amount of TGF-ß1 with the highest values in the EDTA/NB/XP group, followed by EDTA/NB, EDTA/DW/XP, EDTA/DW and Negative Control groups respectively. CONCLUSIONS: The results of this study suggest that NBs can promote the success of REPs since it revealed a significant increase in the TGF-ß1 release following its use in the enhancement of the EDTA solution. A comparable effect was obtained by XP-endo finisher activation of the EDTA solution. The combined use of NBs and XP-endo Finisher can be a promising addition in REPs. Accordingly, Enhancement and activation of the EDTA solution may compensate decreasing the EDTA irrigation time attempted to avoid the deleterious effect of EDTA on dentin.

Comparative effects of 17% ethylenediaminetetraacetic acid and 9% etidronic acid applied with different irrigant activation techniques on the release of growth factors from dentin: in vitro study.

BACKGROUND: Growth factors embedded in the extracellular matrix of the dentin play an important role in the migration, proliferation, and differentiation of dental pulp stem cells in regenerative endodontics. In regenerative endodontic treatments, the type of irrigation solution used is crucial for the release of growth factors (GFs) from the dentin matrix. This study evaluated the effectiveness of different irrigant activation techniques (IAT) using two different chelating agents, 17% ethylenediaminetetraacetic acid (EDTA) and 9% etidronic acid (HEDP), in terms of their GF release. METHODS: Seventy-two mandibular premolar teeth were prepared to simulate an open apex. The root fragments were irrigated with 20 ml of 1.5% sodium hypochlorite and 20 ml of saline solution. Eight root fragments were randomly separated for the control group, and the remaining 64 fragments were randomly separated into eight groups based on two different chelating agents (17% EDTA and 9% HEDP) and four different IAT ((conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI), sonic activation with EDDY, and XP-endo Finisher (XPF)). TGF-ß1, VEGF-A, BMP-7 and IGF-1 release levels were determined using an ELISA, and statistical analysis was performed using the Kolmogorov-Smirnov test, ANOVA, and the Tukey test (p < .05). RESULTS: Compared to the control group, the experimental groups showed significantly higher GF release when using EDTA or HEDP. Among the activation groups, the EDDY group triggered the highest GF release, and the CNI group triggered the lowest. CONCLUSIONS: IAT with EDTA and HEDP can increase GF release, with EDDY being the most effective IAT method. Using chelating agents with IAT may be beneficial in regenerative endodontic treatments.

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.

Review of guidance for the selection of regenerative endodontics, apexogenesis, apexification, pulpotomy, and other endodontic treatments for immature permanent teeth.

This review guidance is a work in progress because the limitations of regenerative endodontics are still being discovered. The endodontic treatments for immature permanent teeth with a necrotic pulp can vary considerably among endodontic practitioners. Whereas, regenerative endodontic treatments are growing in popularity and are creating ever more complex treatment protocols, involving revascularization and/or autologous platelet-rich plasma and scaffolds to elicit host stem cell de novo tissue formation to reestablish the vitality of immature teeth for the purpose of continuing root maturation. Despite much evolving controversy about their potential benefits, risks, prognosis, and contraindications, this review is aimed to discuss how to ensure that regenerative endodontic treatments are successful, by strictly adhering to case selection criteria, and following precise steps to accomplish and monitor the success of the treatment. A review of the endodontic literature was performed, together with practical observations of the problems and outcomes of performing regenerative endodontic treatments. Traditionally, apexification has long been the treatment of choice provided to immature teeth with a necrotic pulp. Regenerative endodontics may be provided as an alternative to apexification, if the tooth and patient meet all the case selection criteria, and if there are no contraindications. Regenerative endodontics has the unique potential advantage of being able to continue the root development in immature permanent teeth, thereby potentially saving the teeth for the lifetime of the patient. Whereas, conventional endodontic root canal treatment, Cvek partial pulpotomy, apexogenesis, and apexification, should always be provided when these treatments are more likely to benefit the patient because they can be more successful than regenerative endodontics.

Patient-centric outcome assessment of endodontic microsurgery using periapical radiography versus cone beam computed tomography: A randomized clinical trial.

AIM: This study aimed to evaluate whether utilizing additional cone beam computed tomography (CBCT) imaging has any effect on quality of life and healing outcome following periapical surgery compared with periapical radiographs (PR). METHODOLOGY: The study was registered in ClinicalTrials.gov (NCT04333940). In this parallel group randomized controlled trial, 52 patients (88 teeth) with persistent apical periodontitis and periapical radiographic evidence of periapical lesion were randomly assigned to either PR or CBCT group. The primary predictor was the type of the imaging method (PR only or with additional CBCT). The primary outcome was patient's quality of life during the first week after periapical surgery and the secondary outcomes were duration of surgery and healing outcome at 12-month follow-up. Participants of both groups received periapical surgery based on the pre-surgical plan provided by the radiographic imaging methods. Quality of life (QoL) was assessed using Modified Shugars questionnaire. Radiographic analysis for healing was conducted using Molven's criteria and modified PENN 3D criteria. The categorical data between groups were analysed using the Chi-square test, whilst intragroup comparisons were analysed using the McNemar test. The average scores for each component of QoL (oral functions, general functions, pain, swelling and other symptoms), combined QoL scores (overall average of values of 13 variables) and analgesic usage on each day were calculated and analysed. RESULTS: At 12 months of follow-up, fifty patients were evaluated. Participants in PR group reported significantly more swelling on first three days compared with CBCT group. The analgesic use was higher in the PR group on 2nd and 3rd day (Mann-Whitney U test with Bonferroni correction; p < .007). A significant difference in the limitation of general functions was observed at the second day (p < .07) with the higher values in the PR group. The combined QoL score between the two groups was found to be non-significant. However, none of the patients experienced intraoperative complications or neurovascular exposure. The mean surgical time was lesser in the CBCT group (p < .05). Radiographic healing revealed a success rate of 96.2% for the PR group and 95.8% for the CBCT group with no significant difference between the groups. CONCLUSION: Participants in the CBCT group experienced substantially less early postoperative swelling and limitation in general functions, in comparison with the PR group. However, preoperative CBCT had no effect on other QoL parameters and intraoperative complications in medium-risk patients. Furthermore, CBCT did not exhibit any added advantage over periapical radiography in terms of assessing healing outcome following endodontic microsurgery. CBCT offered surgically relevant anatomic information for pre-surgical planning and ensured the treatment rendition with a significantly reduced operative time.

Evaluation of postoperative pain and healing following regenerative endodontics using platelet-rich plasma versus conventional endodontic treatment in necrotic mature mandibular molars with chronic periapical periodontitis. A randomized clinical trial.

AIM: To evaluate the post-operative pain and the healing of necrotic mature permanent mandibular molar teeth with peri-apical periodontitis after conventional endodontic treatment versus after platelet-rich plasma (PRP) revascularization. METHODOLOGY: The protocol of this randomized clinical trial was registered at www. CLINICALTRIALS: gov with identification number NCT03350841. Twenty-eight patients were included in the study after confirming the diagnosis clinically and radiographically. In the first visit, mandibular molar teeth of both groups were mechanically prepared. Double antibiotic paste was prepared and injected then the cavity that was sealed with glass ionomer. At the second visit, the patients were randomized either to control group where standard endodontic treatment was completed by lateral condensation technique or assigned to intervention group where PRP revascularization technique. The degree of spontaneous pain was assessed using numerical rating scale (NRS) pre-operatively, then post-operatively after 6, 12 h and daily for 5 days. Patients were given a placebo to be administrated in case of pain. An analgesic (ibuprofen 400mg) was prescribed in case of persistent pain. Clinical and radiographic healing was assessed after 6 and 12 months. All demographic, baseline and outcome data were collected and statistically analysed. RESULTS: Regarding the post revascularization/obturation pain, there was no statistically significant difference between severity of pain in the two groups at all time intervals except after 12 h, revascularization group showed statistically significantly higher prevalence of no pain than endodontic treatment group. Regarding the healing; the periapical lesions decrease in size significantly from the pre-operative lesion size in both groups without significant difference between the both groups. CONCLUSION: Within the limitation of this study, PRP revascularization could be an alternative treatment to root canal treatment but further randomized clinical trials with standardized techniques and long follow up periods are recommended for more reliable results.

Clinical and radiographic outcomes of regenerative endodontic procedures for traumatized permanent necrotic teeth with apical periodontitis and external root resorption.

AIM: This clinical study was undertaken to assess the effect of treatment with regenerative endodontic procedures (REPs) on 20 teeth with pulp necrosis, apical periodontitis, and external root resorption (ERR). METHODOLOGY: Teeth were treated with REPS utilizing the American Association of Endodontists (AAE) protocol. Quantitative assessment of changes in radiographic root area (RRA) were statistically analysed to assess changes in root dimensions after an average follow-up period of 3 years. RESULTS: All 20 teeth survived, 14 teeth (70%) were classified successful, and only 1 tooth (5%) failed throughout the study period. Based on the radiographic examination, all 20 teeth showed complete repair of the periapical lesions and arrested ERR. However, 5 teeth (25%) subsequently developed replacement resorption. The RRA between baseline and 3-year follow-up showed a significant difference for the total 20 teeth (p = .009). An analysis according to the trauma type and the extra-oral time showed the RRA increase was significantly different in the non-avulsion group (p = .015) and for the avulsion group with an extra-oral time less than 60 min (p = .029). The RRA increase was not statistically significant in the avulsion group of extra-oral time more than 60 min (p = .405). Nine teeth (45%) and 10 teeth (50%) responded to cold and electric pulp testing, respectively. CONCLUSIONS: Within the limitations of this study, the favourable outcomes of REPs were further confirmed for traumatized permanent necrotic teeth with ERR in terms of periapical lesion healed and a significant increase in RRA. The study contributes further evidence of the role of REPs in arresting ERR.

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.

Effects of EDTA and saline as the final irrigation in regenerative endodontic procedures on the migration, proliferation, and differentiation of human stem cells from the apical papilla.

OBJECTIVES: To evaluate the effect of EDTA and saline as the final irrigation in regenerative endodontic procedures (REPS) on the attachment, proliferation, migration, and differentiation of stem cells from the apical papilla (SCAPs). MATERIALS AND METHODS: Dentin specimens from 140 human third molars were irrigated with various protocols-group 1: normal sterile saline (NSS), group 2: EDTA, group 3: EDTA then 5 mL NSS, or group 4: EDTA then 20 mL NSS. The specimens were used in cell assays. For cell proliferation, SCAPs were seeded on dentin, and the cell viability on days 1, 3, and 7 was determined using an MTT assay. At day 3, the attached cells' morphology was observed using SEM, and cell migration was investigated using a transwell migration assay. The ALP activity and odonto/osteogenic differentiation gene expression were evaluated at days 7, 14, and 21 using an ALP activity assay and RT-qPCR. RESULTS: On days 3 and 7, group 4 demonstrated more viable cells than group 1 (p < 0.01). The amount of migrated cells in groups 2, 3, and 4 was greater compared with group 1 (p < 0.05). Moreover, SCAP differentiation was similar between groups. CONCLUSIONS: Irrigating dentin with EDTA alone or with EDTA then NSS promoted SCAP migration. However, a final irrigation with 20 mL NSS after EDTA promoted SCAP proliferation without affecting their differentiation. CLINICAL RELEVANCE: When using a blood clot as a scaffold, a final flushing with 20 mL NSS after EDTA could be beneficial for clinical REP protocols.

Regenerative endodontic treatment using autologous blood from alveolar bone for mature permanent premolar with apical periodontitis: a case report.

OBJECTIVE: The formation of blood clot, achieved through periapical bleeding or the use of peripheral venous blood, platelet-rich plasma (PRP) or platelet-rich fibrin (PRF), has been widely utilized in regenerative endodontic procedures (REPs). Except for inducing periapical bleeding, the scaffolds obtained from PRP, PRF, and venous blood are not derived from oral and maxillofacial tissues. In this case report, autologous blood clots from alveolar bone were described, which involved puncturing the maxillary terminal alveolar bone. The purpose of this case report was to assess the efficacy of the alveolar-derived blood clot in regenerative endodontic procedures in a mature permanent premolar. METHODS: A mature premolar had a fractured central cusp, one of the developmental aberrations of tooth, without a proper treatment, resulting in chronic periapical lesion. To address this condition, REPs were employed, utilizing blood obtained through aspiration from the maxillary terminal alveolar bone aspiration. RESULT: Follow-up examinations of tooth #29 revealed the absence of clinical symptoms, a progressive resolution of a periapical lesion area and thickening of the root canal walls. CONCLUSION: This case demonstrated that blood clot obtained through paracentesis of the maxillary terminal alveolar bone could be successfully applied in REPs and has potential to manage periapical lesions. However, further and more clinical trials are required to verify the feasibility of the alveolar-derived blood clot in REPs and compare the outcome of alveolar-derived blood clot with currently used biological scaffolds. CLINICAL RELEVANCE: In comparison to PRP or PRF from peripheral venous blood, blood clots obtained via paracentesis of the maxillary terminal alveolar bone could be administrated by dentists, eliminating the need for reliance on professional nurses. The use of blood clots from alveolar bone could simplify the REPs in cases where periapical blood was insufficient to brim the root canals.

Evaluation of the effectiveness of different treatment approaches in preventing coronal discoloration caused by regenerative endodontic treatment.

OBJECTIVES: This study aimed to evaluate the effectiveness of Teethmate desensitizer, a dentin bonding agent (DBA), Nd:YAG laser, and Er:YAG laser, which provides dentin tubule occlusion in the pulp chamber with different mechanisms, in preventing tooth discoloration due to regenerative endodontic treatment. MATERIALS AND METHODS: One hundred five extracted maxillary human incisors with single roots and single canals were included in the study. The apical third of each tooth was resected below the enamel-cementum junction (CEJ) to obtain a standard root length as 10 ± 1 mm. Root canal preparation was performed using the ProTaper Next files up to X5. Root canals were prepared with Gates Glidden (# 2-4) burs to simulate the immature root apex and an apical diameter of 1.1 ± 0.1 mm was obtained. The teeth were randomly divided into 7 groups (n = 15): DBA, Teethmate, Nd:YAG, Er:YAG, Biodentine, Blood, and Negative Control. Relevant dentin tubule occlusion methods were applied to DBA, Teethmate, Nd:YAG, and Er:YAG groups. Following dentin tubule occlusion procedures, Biodentine was placed on the blood clot after filling the root canals with blood up to 4 mm below the CEJ. No dentin tubule occlusion procedure was applied for Blood and Biodentine groups. Color measurement was performed with the spectrophotometer Vita Easyshade Advance before treatment, immediately after treatment, and at days 7, 30, and 90. Data were converted to L*a*b color values of Commission International de I'Eclairage (CIE L*a*b) and ΔE values were calculated. Two-way ANOVA and post hoc Tukey test (p = 0.05) were performed for statistical analysis. RESULTS: A clinically detectable color change was observed in all groups except for the negative control (ΔE ≥ 3,3). It was observed that Biodentine used alone has a potential for discoloration. It was determined that as the contact time with blood increased, tooth discoloration increased. However, no significant difference was found between dentin tubule occlusion methods in preventing color change (p > 0.05). CONCLUSIONS: It was determined that no dentin tubule occlusion method could 100% prevent discoloration caused by RET. CLINICAL RELEVANCE: DBA and Teethmate, which do not have a significant difference in terms of preventing color change, are considered to be suitable for dentin tubule occlusion due to their ease of application and low cost compared to Nd:YAG laser and Er:YAG laser.