Regenerative Endodontics Research Articles

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.

Triple Antibiotic Paste: A Game Changer in Endodontics.

Triple antibiotic paste has emerged as a game changer in the field of endodontics, offering a novel approach to the management of refractory endodontic infections and regenerative endodontics. This review article provides an overview of the composition, mechanism of action, clinical applications, advantages, and potential limitations of triple antibiotic paste in endodontic therapy. Additionally, recent advancements and future directions for the use of triple antibiotic paste in endodontics are also discussed.

Effect of Boswellic Acid on Viability of Dental Pulp Stem Cells Compared to the Commonly Used Intracanal Medications: An In Vitro Study.

This study was aimed at evaluating the effect of acetyl-11-keto-β-boswellic acid (AKBA) on dental pulp stem cells (DPSCs) viability and proliferation to be used as a potential root canal medicament. Dental pulp stem cells were isolated from human third molars. The phenotypic characterization of DPSCs was verified by flow cytometry analysis. The viability assay was performed using the methyl-thiazoltetrazolium (MTT) assay. Cells were treated with different concentration of triple antibiotic paste (TAP) and calcium hydroxide Ca(OH2) (5, 2.5, 1, 0.5, and 0.25 mg/mL), AKBA (10, 5, 1, 0.1, and 0.01 µM). All experiments were done in separate triplicate experiments. Results: Dental pulp stem cells were characterized by flow cytometry. Cells treated with Ca(OH)2 (1, 2.5, and 5 mg/mL) showed significantly reduced viability compared with the control cells (p < 0.05). Dental pulp stem cells treated with 1, 2.5, and 5 mg/mL TAP resulted in a significant decrease in viability (p < 0.05). Cells treated with AKBA in concentrations (1, 0.1, and 0.01 µM) demonstrated higher viability than the control group (p < 0.05), while AKBA in concentrations (5 and 10 µM) showed equal or decreased viability than the control group. (p > 0.05). Regarding cell density assay, AKBA showed significant increase in cell density after 5 and 7 days compared with cells medicated with TAP and Ca(OH)2 while TAP revealed marked reduction in cell density in all the tested intervals. Acetyl-11-keto-β-boswellic acid in lower concentrations (0.01, 0.1, and 1 µM) demonstrated superior cell viability than TAP and Ca(OH)2, and it may possess the potential to be an intracanal medicament in regenerative endodontics. Studying the effect of different potential root canal medicaments and their capability to induce DPSCs proliferation might be of value. The influence of AKBA on the viability and proliferation of DPSCs tested in this study sheds light on its use as a potential intracanal medication especially in regenerative endodontics. How to cite this article: Amer NA, Badawi MF, Elbeltagi MG, et al. Effect of Boswellic Acid on Viability of Dental Pulp Stem Cells Compared to the Commonly Used Intracanal Medications: An In Vitro Study. J Contemp Dent Pract 2023;24(12):957-966.

Two-Dimensional Radiographs and Cone-beam Computed Tomography Assessment of Concentrated Growth Factor and Platelet-Rich Fibrin Scaffolds in Regenerative Endodontic Treatment of Immature Incisors with Periapical Radiolucency: A Randomized Clinical Trial

IntroductionThe primary aim of this study was to compare the radiographic changes of immature incisors with periapical radiolucency after treatment with platelet-rich fibrin (PRF) and concentrated growth factor (CGF) platelet concentrate scaffolds as well as assessment of the clinical success rate over 12 months. The secondary aim was to monitor the radiographic changes in terms of reduction of periapical lesion diameter (PALD), root dentine thickness (RDT), root length (RL), and apical foramen width (AFW). The tertiary aim was to assess and pulp responses, after 12 months. MethodsFifty six children with seventy necrotic, single-rooted maxillary incisors with periapical radiolucency were treated with either CGF or PRF scaffolds (35 teeth per group). Two patients with 4 teeth (2 teeth in each group) failed to attain the follow-up recalls. Radiographic changes in terms of reduction of PALD, RDT, RL, and AFW were monitored using a 2-dimensional (2D) radiograph and cone-beam computed tomography (CBCT) scan. The clinical performance of teeth receiving both scaffolds was assessed after 6 and 12 months. Categorical and continuous data were analyzed using the chi-square test and the t test, respectively. The time and group effects on the means of different radiographic dimensions were tested using the general linear model. Bland-Altman plots were used to assess the level of agreement between the 2D radiographs and CBCT. The level of significance was defined at 0.05 and a 95% confidence interval. ResultsThe means of PALD and RL showed significant enhancement in the CGF group compared to the PRF group (P < .05). While the difference between the 2 scaffolds in terms of RDT and AFW was not significant (P > .05). The findings of the 2D radiograph and CBCT were consistent. Clinically, both scaffold success rates were similar (93.9%) over the follow-up intervals. The influence of study independent variables had no significant effect on the success of the regenerative endodontic procedures outcome (P > .05). There was no significant difference in the positive pulp responses to the thermal and electric pulp tests after one year of treatment (P > .05). ConclusionsAccording to the short-term follow-up, PRF and CGF were successful in treating immature teeth with periapical radiolucency by regenerative endodontics. Both scaffold systems induced periapical healing and root lengthening with significant superiority of CGF.

Current Aspects of Regenerative Endodontics: A Systematic Review

Relevance. The modern concept of endodontic treatment in most clinical cases involves extirpation of the pulp with the loss of its plastic, trophic, sensory, and protective functions. In this regard, the search for ways to recreate lost cells and the main substance of the pulp and periodontium to replace the intraradicular space with “vital” tissue. Regenerative endodontics based on the principles of tissue engineering and offers techniques for restoring damaged tissues of the pulp-dentin complex based on the use of stem cells, growth factors, and an organic matrix. Aim. Systematize information presented in scientific articles about research conducted, opportunities and development prospects in the field of regenerative endodontics. Materials and methods. A search of literature sources was carried out in the PubMed, dissercat.com, elibrary database.ru, cyberleninka.ru, by keywords, “regenerative endodontics”, “stem cells”, “growth factors”, “pulp-dentin complex” with a choice of article types “Clinical Trial”, “Meta-Analysis”, “Review”, "Systematic Review". Results. After analyzing the literature review, an idea was obtained about the current stage of development of regenerative endodontics, preclinical and clinical studies on the restoration of the pulp-dentin complex. Clinical cases based on the triad of regenerative endodontics are presented, as well as an algorithm for performing these therapeutic procedures. Conclusions. Regenerative endodontics is a rapidly developing discipline whose clinical advances are primarily related to the treatment of immature tooth roots, which results in continued root development. Subsequent scientific research is aimed at obtaining significant results in the treatment of a fully formed permanent tooth, which will ensure a unique restoration of the immunological, sensory and protective properties of the pulp-dentine complex.

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

IntroductionDental 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. MethodsPatients 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. ResultsBased 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. ConclusionsTransplantation 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.

Innovative approaches in regenerative endodontics

Background: Biomimicry or biomimetics refers to developing materials and techniques inspired by natural systems. In dentistry, this approach aims to replicate natural tooth structures and functions, addressing limitations of conventional materials and techniques. Regenerative endodontics, including cell homing and revascularization, represents significant advancements in this field, focusing on pulp-dentin regeneration and tooth vitality restoration. Aim: This review explores innovative biomimetic approaches in regenerative endodontics, including the latest techniques and their clinical implications. It aims to assess the effectiveness and future prospects of these methods in enhancing tooth repair and regeneration. Methods: The review synthesizes current literature on regenerative endodontic procedures, including cell homing, revascularization, scaffold implantation, and gene therapy. It examines experimental studies, clinical trials, and advancements in biomimetic materials and techniques, highlighting their applications and outcomes. Results: The review finds that regenerative endodontics has evolved from traditional apexification to advanced techniques such as cell homing and revascularization. Cell homing, which leverages the body’s natural healing processes without cell transplantation, shows promise in generating pulp-dentin tissue. Revascularization, involving the induction of a blood clot and stem cell recruitment, has demonstrated potential in restoring vitality to necrotic teeth.

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.

Regenerative Endodontic Treatment: A Bibliometric Analysis of Global Indian Author’s Research Contribution from 2000 to 2023

Aim: Regenerative endodontic (RE) treatment is a new paradigm shift in the management of non-vital or necrotic immature young permanent teeth and has been substantiated by numerous research publications in the endodontic literature. Methods: A bibliographic database search was performed using PUBMED and Google Scholar for the published articles from 2000 to March 2024. All articles published in the English language only in this period were selected constituting only Indian authors who are working within India, their affiliations, working specialty, Indian institutions//College/University, gender, state of origin of the published article, and journal name with its impactor factor. The obtained data was tabulated and analysed for the estimation of bibliometric details. Results: The estimated Indian author's contribution towards RE on a global level was 3.34% with maximum original studies (N=11). Saveetha Dental College was found with highest publication (N=4). International Journal of Clinical Pediatric Dentistry (N=4) conquered the first place with maximum publications followed by Cureus (N=3). Karnataka state (N=7) and south zone (N=20) were found with maximum research output. Conservative Dentistry (N=17) and Pediatric and Preventive Dentistry specialty (N=11) were crowned with the highest research publications towards RE. Conclusion: The present bibliometric analysis showed that although there is growing interest and trend among Indian researchers/authors in the utilisation of RE, however, there are insufficient evidence-based results on this domain.

Laser Applications in Regenerative Endodontics: A Review.

Introduction: Developing regenerative endodontic treatment (RET) is an exciting approach to managing immature permanent teeth with pulp necrosis. RET is usually performed in two clinical steps: disinfection (first step) and tissue engineering (second step). Recently, laser therapy has entered the field of RET. This study aimed to provide an overview of the literature that employed laser therapy for root regeneration. Methods: A comprehensive search was performed on four databases, including PubMed, Web of Science, Scopus, and Google Scholar. The searched keywords were laser, regenerative endodontics, immature permanent teeth, and dental pulp necrosis, and related English-published articles were included up to October 2023. Results: Thirteen studies utilized a laser for RET. In the first step of RET, both high-power and low-level lasers (through photodynamic therapy [PDT]) may be applied for canal disinfection. In contrast, regenerative procedures in the second step of RET are just accelerated by low-power lasers (biostimulation). The literature does not support the benefit of laser-assisted irrigation in improving the clinical success of RET. There is some evidence that laser-assisted disinfection with a diode laser may provide comparable results to triple antibiotic paste in reducing bacterial counts in root canals while providing slightly better clinical and radiographic outcomes. PDT may be an effective and suitable adjunct to conventional disinfection methods in immature, necrotic teeth. Conclusion: Low-power lasers may be beneficial tools for improving the results of regenerative endodontics through chemical disinfection in the first step (PDT) or by biostimulation in the second step of RET.

Pediatric endodontic considerations in the application of regenerative therapy for immature permanent teeth: a review article

For adult teeth with necrosis or apical periodontitis, regenerative endodontics provides a useful alternative to standard endodontic treatment. This review focuses on the pediatric endodontic considerations in the application of regenerative therapy for immature permanent teeth. A thorough literature search was conducted in the MEDLINE database using the keywords &amp;quot;pediatric, regenerative, therapy, endodontics, immature, permanent, and teeth&amp;quot; to find relevant publications published between 2017 and 2024. Additionally, Google Scholar was used to find and access pertinent scientific publications using the appropriate search terms. Various inclusion criteria were applied to select the articles for review. The selected articles were published between 2020 and 2024 and included discussions on several specific elements. Topics covered include the criteria for case selection for regenerative endodontics. Overall, the existing evidence indicates that using regenerative endodontic techniques to treat adult permanent teeth with apical periodontitis or necrosis may successfully lead to the resolution of apical translucencies and the absence of clinical signs and symptoms. With slight modifications to the clinical procedure, regenerative dentistry methods can be effectively applied to specific cases, such as those involving a small apical foramen, decreased blood supply, and a lack of growth factors. However, additional research is required to determine the optimal conditions for achieving successful treatment outcomes.

The effect of injectable platelet-rich fibrin and platelet-rich fibrin in regenerative endodontics: a comparative in vitro study.

To explore the feasibility of injectable platelet-rich fibrin (i-PRF) in regenerative endodontics by comparing the effect of i-PRF and platelet-rich fibrin (PRF) on the biological behavior and angiogenesis of human stem cells from the apical papilla (SCAPs). i-PRF and PRF were obtained from venous blood by two different centrifugation methods, followed by hematoxylin-eosin (HE) staining and scanning electron microscopy (SEM). Enzyme-linked immunosorbent assay (ELISA) was conducted to quantify the growth factors. SCAPs were cultured with different concentrations of i-PRF extract (i-PRFe) and PRF extract (PRFe), and the optimal concentrations were selected using the Cell Counting Kit-8 (CCK-8) assay. The cell proliferation and migration potentials of SCAPs were then observed using the CCK-8 and Transwell assays. Mineralization ability was detected by alizarin red staining (ARS), and angiogenesis ability was detected by tube formation assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of genes related to mineralization and angiogenesis. The data were subjected to statistical analysis. i-PRF and PRF showed a similar three-dimensional fibrin structure, while i-PRF released a higher concentration of growth factors than PRF ( P <.05). 1/4× i-PRFe and 1/4× PRFe were selected as the optimal concentrations. The cell proliferation rate of the i-PRFe group was higher than that of the PRFe group ( P <.05), while no statistical difference was observed between them in terms of cell mitigation ( P >.05). More importantly, our results showed that i-PRFe had a stronger effect on SCAPs than PRFe in facilitating mineralization and angiogenesis, with the consistent result of RT-qPCR ( P <.05). This study revealed that i-PRF released a higher concentration of growth factors and was superior to PRF in promoting proliferation, mineralization and angiogenesis of SCAPs, which indicates that i-PRF could be a promising biological scaffold for application in pulp regeneration.

Update on chelating agents in endodontic treatment: A systematic review.

The aim of this review was to assess the evidence regarding the most commonly used chelating agents in terms of efficacy, erosive potential, cytotoxicity, interaction, antimicrobial effect, impact on sealers adhesion, and release of growth factors. MEDLINE (PubMed) database, Cochrane Library and Scopus were searched up to January 14, 2023, including studies with one or more of the following chelating agents: 17% EDTA, 9% and 18% HEDP, 10% and 20% citric acid, 2%-2.25% peracetic acid and 7% maleic acid. In addition, the reference lists of all selected articles were also checked to identify additional relevant studies. Articles published in English and available in full-text were selected. The quality of studies was assessed using the modified CONSORT checklist guide and the Cochrane Collaboration tool. The electronic search yielded 538 citations, 56 of which were included. The articles included had moderate and low evidence values. Among 56 articles included, 55 were in vitro studies and one was a randomized clinical trial. Among the in vitro studies, 15 evaluated efficacy and dentin erosion, 12 evaluated interaction with other endodontic irrigants, 9 tested antimicrobial effect, 4 evaluated cytotoxicity in hamster and rat lung cells, 9 evaluated intervention in adhesion of filling materials and 8 focused on release of growth factors and on behavior of stem cells in regenerative endodontic. The RCT tested antimicrobial effect. 17% EDTA is the most effective in smear layer removal and in releasing growth factors on regenerative endodontics. However, the current incorporation of 9% and 18% etidronic acid has shown optimal results due to its compatibility with sodium hypochlorite and its capability on avoiding smear layer formation through a continuous chelation action. Despite these preliminary findings, methodological standardization between studies is required and in vivo studies are necessary to confirm in vitro studies. Key words:Chelating Agents, Smear Layer, Systematic Review, Endodontics, Root Canal Irrigants.

Regenerative endodontics: repair or true regeneration? A narrative review

Regenerative endodontics: repair or true regeneration? A narrative review

Clinical evaluation of a new laser enhanced ablation procedure (LEAP) in regenerative endodontics: a case report

Clinical evaluation of a new laser enhanced ablation procedure (LEAP) in regenerative endodontics: a case report

Advancements and challenges in stem/progenitor cell transplantation for dentin-pulp regeneration: a systematic review of animal studies (part I).

Dentin-pulp regeneration through stem/progenitor cell transplantation represents a promising frontier in regenerative endodontics. This systematic review meticulously evaluates animal studies to investigate the efficacy of stem cell therapy in repairing/regenerating the dentine-pulp complex in mature/immature animal teeth. Employing a comprehensive electronic search of PubMed and Scopus databases up to October 2023, relevant English studies were identified/assessed. Evaluation parameters encompassed radiographic and histological assessments of dentin-pulp complex formation. Outcome measures included pulp-like and dentin-like tissues regeneration, apical healing, dentin thickening, apical closure, and dentinal bridge formation. The risk-of-bias assessment adhered to the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) guidelines. Out of 3250 identified articles, 23 animal experiments were included, categorized into regenerative procedures in mature teeth (n=11), regenerative procedures in immature teeth (n=4), and vital pulp therapy (n=8). Despite the promising potential, the bias in the included studies was high. Notably, Various scaffolds, and growth factors were employed, highlighting the heterogeneity across the studies. Dental pulp stem cells (DPSCs) and bone marrow stem cells, especially specific subfractions, demonstrated notable regenerative potential: hypoxic conditions and extracellular vesicles from preconditioned DPSCs enhanced regeneration, with considerations of cell fate. Donor age impacted regeneration, and challenges persisted in pulpotomy and direct pulp capping. Scaffold and growth factor choices influenced outcomes, underscoring the need for standardized strategies. Despite the promise, clinical viability faces hurdles, necessitating further investigation into adverse effects, optimized scaffolds, and regulatory considerations. This systematic review illuminates the potential of stem cell transplantation for dentin-pulp complex regeneration. The overall evidence quality, influenced by study heterogeneity and biases, underscores the need for cautious interpretation of findings. Future studies should refine methodologies and establish reliable histological parameters for meaningful advancements in dentin-pulp regeneration.

Comparison between Calcium Hydroxide with Mineral Trioxide Aggregate and Regenerative Endodontics in Inducing Root Apex Closure during Apexification – A Systematic Review and Meta-analysis

Abstract This study aimed to assess better effectiveness between regenerative endodontic procedures (REP) and apexification procedures (AP) with mineral trioxide aggregate (MTA) and calcium hydroxide for inducing root end apex closure. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed and registered in PROSPERO-CRD42023398997. Electronic databases were searched for studies evaluating effectiveness of REP and AP in terms of survival rate, success rate, increase in root length, root width and decrease in apical diameter. Cochrane risk of bias (RoB) -2 tool was used for quality assesssment using RevMan 5.3. The risk ratio (RR) and standardized mean difference (SMD) was used as summary statistic measure with random effect model (P &lt; 0.05). Nine studies were included in qualitative synthesis and eight studies for meta-analysis. Quality assessment revealed moderate to low risk of bias. The pooled estimate through RR and SMD favoured REP being superior to AP for better survival rate (RR = 1.01 (0.96 – 1.06)), success rate (RR = 1.09 (0.96 – 1.24)), increase in root length (SMD = 0.25 (-0.14 – 0.63)), root width (0.66 (0.22 – 1.10)) and decrease in apical diameter (SMD =0.66 (-0.51 – 1.83)). Funnel plot did not show any heterogeneity indicating absence of publication bias. REP significantly improved apical root end closure. AP are equally effective in forming calcific barrier, however it was concluded that regeneration procedures are comparably superior to apexification procedures with greater outcomes. Clinicians should consider employing the REP in cases when root development is severely deficient and where tooth’s prognosis is hopeless even with an apexification procedure.

Advancing dentin-pulp regeneration: clinical perspectives and insights from stem/progenitor cell transplantation (part II).

This systematic review evaluates clinical studies investigating regenerative endodontic procedures for mature/immature teeth utilizing stem cell transplantation. An electronic search of Scopus, PubMed, ISI Web Science, and Google Scholar was conducted up to January 2023. Outcome measures encompassed radiographic (periapical lesion, root length, apical foramen width, volume of the regenerated pulp) and clinical (post-operative pain, sensibility test) parameters. Among 3250 identified articles, five clinical studies were selected, comprising two randomized controlled trials (RCTs) for mature/immature teeth, and three case reports/series for mature teeth. Despite the promising potential, the included studies exhibited a notable risk of bias. The diversity in stem cells (e.g., dental pulp stem cells [DPSCs], umbilical cord mesenchymal stem cells [UC-MSCs]), scaffolds (Atecollagen, collagen membrane, platelet-poor plasma [PPP], leukocyte platelet-rich in fibrin [L-PRF]), and growth factors (granulocyte colony-stimulating factor [G-CSF]) emphasized the heterogeneity across interventions. In RCTs, DPSCs application increased root length and reduced apical foramen width in immature teeth, while UC-MSCs transplantation reduced apical lesions in mature teeth. Transplantation of DPSCs aggregates or UC-MSCs/PPP also elicited positive pulp responses and increased blood flow. In case reports/series, DPSCs application in teeth with irreversible pulpitis resulted in mineralization and increased the regenerated pulp' volume. Furthermore, transplantation of DPSCs with G-CSF/atelocollagen or L-PRF/collagen membrane led to positive pulp responses. While underscoring the potential of stem cell transplantation for regenerative endodontics in mature/immature teeth, the overall evidence quality and the limited number of available studies emphasize the need for cautious interpretation of results. Future well-designed clinical studies are essential to validate these findings further.

Micro-computed tomography (micro-CT) evaluation of root canal morphology in immature maxillary third molars.

The endodontic treatment of immature permanent teeth with necrotic pulp is a significant clinical challenge. The success of regenerative endodontic procedure is highly dependent on disinfection of the root canal and an accurate anatomical knowledge of the root canal. The aim of this study was to use micro-computed tomography (micro-CT) analysis to investigate the configuration of root canals in the upper permanent third maxillary molars with incomplete root development in their coronal, apical and middle third portions. Thirty immature third permanent maxillary molars were scanned using a micro-CT system. Then, we measured the diameters and areas of the root canal in the coronal, middle and apical third of the roots. The ratio between the long and short diameter of each root canal was then calculated and the canals were divided into several groups: round, oval, long oval, flat and irregular. The round configuration was not observed in the distobuccal and mesiobuccal roots in any of their anatomical regions. Oval and long oval canals predominated in the distobuccal root. The greatest variations were observed in the mesiobuccal root, with the ribbon-shaped canal predominating in the middle region and an irregular shape in the apical region. In the coronal region of the palatal canal, the round configuration predominated; in the middle third, we observed an almost equivalent distribution between round and oval configurations; apically, the oval shape predominated. In conclusion, we observed significant complexity and variation in the morphology and configuration of root canals in immature permanent molars, thus generating additional obstacles for the success of regenerative endodontics.

Case series on two-stage disinfection in regenerative endodontics on permanent mandibular molar with blunderbuss canal

Background: Revascularization is a promising approach as it promotes root end closure forming healthy, thick root dentin at the apex which provides clinical and radiographic success due to the elimination of bacteria and disinfection of the canal which gives a 100% sterile environment to receive SCAP. Aim: To examine the effect of a regenerative endodontic procedure on immature necrotic teeth with apical periodontitis Method: An 8-year-old medically fit boy was referred to the department with a lingering type of pain in the immature permanent mandibular first right molar. Bleeding was induced in the root canals at the third appointment. The blood clots (scaffolds) were covered with MTA, and the tooth was restored with a composite filling. Recall sessions were scheduled after one month and 3 months, when the tooth appeared asymptomatic clinically and radiographically, with considerable periapical healing. Conclusion: An immature multirooted tooth with necrotic pulps and periapical radiolucency was managed with evident clinical and radiographic success, wherein non-setting calcium hydroxide paste and triple antibiotic paste were used sequentially to guarantee complete canal disinfection.