Regenerative Endodontic Therapy Research Articles

The Use of Nanofibers in Regenerative Endodontic Therapy—A Systematic Review

The Use of Nanofibers in Regenerative Endodontic Therapy—A Systematic Review

Providing biomimetic microenvironment for pulp regeneration via hydrogel-mediated sustained delivery of tissue-specific developmental signals

Regenerative endodontic therapy is a promising approach to restore the vitality of necrotic teeth, however, pulp regeneration in mature permanent teeth remains a substantial challenge due to insufficient developmental signals. The dentin is embryologically and histologically similar to the pulp, which contains a cocktail of pulp-specific structural proteins and growth factors, thus we proposed an optimizing strategy to obtain dentin matrix extracted protein (DMEP) and engineered a DMEP functionalized double network hydrogel, whose physicochemical property was tunable by adjusting polymer concentrations to synchronize with regenerated tissues. In vitro models showed that the biomimetic hydrogel with sustained release of DMEP provided a beneficial microenvironment for the encapsulation, propagation and migration of human dental pulp stem cells (hDPSCs). The odontogenic and angiogenic differentiation of hDPSCs were enhanced as well. To elicit the mechanism hidden in the microenvironment to guide cell fate, RNA sequencing was performed and 109 differential expression of genes were identified, the majority of which enriched in cell metabolism, cell differentiation and intercellular communications. The involvement of ERK, p38 and JNK MAPK signaling pathways in the process was confirmed. Of note, the in vivo model showed that the injectable and in situ photo-crosslinkable hydrogel was user-friendly for root canal systems and was capable of inducing the regeneration of highly organized and vascularized pulp-like tissues in root segments that subcutaneously implanted into nude mice. Taken together, this study reported a facile and efficient way to fabricate a cell delivery hydrogel with pulp-specific developmental cues, which exhibited promising application and translation potential in future regenerative endodontic fields.

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

ObjectiveThe 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. DesignTen 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. ResultsThe 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. ConclusionsThis 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.

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.

Multifunctional Exosomes Derived from M2 Macrophages with Enhanced Odontogenesis, Neurogenesis and Angiogenesis for Regenerative Endodontic Therapy: An In Vitro and In Vivo Investigation.

Exosomes derived from M2 macrophages (M2-Exos) exhibit tremendous potential for inducing tissue repair and regeneration. Herein, this study was designed to elucidate the biological roles of M2-Exos in regenerative endodontic therapy (RET) compared with exosomes from M1 macrophages (M1-Exos). The internalization of M1-Exos and M2-Exos by dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) was detected by uptake assay. The effects of M1-Exos and M2-Exos on DPSC and HUVEC behaviors, including migration, proliferation, odonto/osteogenesis, neurogenesis, and angiogenesis were determined in vitro. Then, Matrigel plugs incorporating M2-Exos were transplanted subcutaneously into nude mice. Immunostaining for vascular endothelial growth factor (VEGF) and CD31 was performed to validate capillary-like networks. M1-Exos and M2-Exos were effectively absorbed by DPSCs and HUVECs. Compared with M1-Exos, M2-Exos considerably facilitated the proliferation and migration of DPSCs and HUVECs. Furthermore, M2-Exos robustly promoted ALP activity, mineral nodule deposition, and the odonto/osteogenic marker expression of DPSCs, indicating the powerful odonto/osteogenic potential of M2-Exos. In sharp contrast with M1-Exos, which inhibited the neurogenic capacity of DPSCs, M2-Exos contributed to a significantly augmented expression of neurogenic genes and the stronger immunostaining of Nestin. Consistent with remarkably enhanced angiogenic markers and tubular structure formation in DPSCs and HUVECs in vitro, the employment of M2-Exos gave rise to more abundant vascular networks, dramatically higher VEGF expression, and widely spread CD31+ tubular lumens in vivo, supporting the enormous pro-angiogenic capability of M2-Exos. The multifaceted roles of M2-Exos in ameliorating DPSC and HUVEC functions potentially contribute to complete functional pulp-dentin complex regeneration.

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

IntroductionEDTA 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. MethodsForty 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%). ResultsAll 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). ConclusionsEDTA 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.

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). 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. 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. 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.

A Comparative Evaluation of Biological Scaffold in Regenerative Endodontic Treatment of Immature Non-Vital Permanent Teeth

Endodontic treatments techniques for immature necrotic teeth include: surgical endodontics, apexification, and singlevisit MTA plug. Regenerative endodontic therapy (RET) is a newer concept that involves restoring the pulp-dentin complex in an infected tooth with an open apex. The aims of this paper were to evaluate RET of immature permanent teeth using biological scaffold and the distinctions between them, with a focus on their ease of manipulation and regenerative potential.

Effect of rapamycin on human periodontal ligament stem cells that have been exposed to sodium hypochlorite

AimsThe present study investigated the effect of rapamycin on the viability and osteogenic differentiation potential of human periodontal ligament stem cells (hPDLSCs) in the presence of sodium hypochlorite (NaOCl). Main methodsAfter determining the minimum inhibitory concentration of NaOCl and optimum concentration of rapamycin, the viability of hPDLSCs was evaluated using the MTT assay subsequent to their exposure to NaOCl, rapamycin, or a combination of both. Osteogenic differentiation was evaluated by the cell mineralization assay performed by alizarin red S staining, alkaline phosphatase activity, and monitoring the expression of osteogenic genes markers Runt-related transcription factor 2, osteocalcin, and osteoprotegerin, using real-time quantitative polymerase chain reaction (RT-qPCR). The expression of autophagy-related genes PI3K, Akt, and mTOR, was also analyzed with RT-qPCR. Key findingsStem cells treated with rapamycin showed the highest percentage of viable cells in the presence of NaOCl. The same trend was observed for all osteogenic differentiation assays. The hPDLSCs treated with rapamycin demonstrated the highest calcium nodule deposition, alkaline phosphatase activity, and the expression of osteogenic gene markers. These effects were not adversely affected by the presence of NaOCl. Rapamycin significantly inhibited mTOR gene expression, while there were no differences in the gene expression of PI3K and Akt. SignificanceRapamycin counteracts the cytotoxic effect of NaOCl by enhancing the viability and osteogenic differentiation potential of hPDLSCs. Rapamycin appears to accomplish these processes via autophagy activation, by inhibiting mTOR gene expression. The incorporation of rapamycin in regenerative endodontic therapy may encourage a higher success rate.

The efficacy of concentrated growth factor and platelet-rich fibrin as scaffolds in regenerative endodontic treatment applied to immature permanent teeth: a retrospective study

BackgroundThe aim of this retrospective study was to compare the efficacy of concentrated growth factor (CGF) and platelet-rich fibrin (PRF) as scaffolds in regenerative endodontic therapy (RET).MethodsNecrotic immature permanent teeth treated with regenerative endodontic therapy during January 2018 to August 2022 were divided into the CGF and PRF groups according to the scaffold. The CGF and PRF groups included 7 and 6 teeth, respectively. The efficacy of regenerative endodontic therapy was analyzed based on the clinical and radiological outcomes at three different follow up periods: T1 (3–6 months), T2 (6–12 months) and T3 (12–24 months). Statistical analysis was performed using the independent T test, Mann-Whitney test and Fisher’s exact test at a significance level of 0.05.ResultsThe success rate of each stage in both groups was 100%. Through quantitative comparison of radiographic outcomes, there was no statistically significant difference between the two groups in terms of root development and periapical lesion healing at each stage, except that the increase rate of radiographic root area in PRF group in the T3 stage was above one in CGF group with statistically significance.ConclusionsBoth CGF and PRF had a similar clinical performance regarding resolution of clinical signs and symptoms, periapical lesion healing, and continued root development as scaffolds in RET. Further prospective studies with large samples for longer follow-up periods are needed.

A 1-year Clinical and Radiographic Assessment of Regenerative Endodontic Therapy for Necrotic Primary Molars: A Randomized controlled Trial.

Preservation of necrotic primary teeth is important. Pulpectomy is the gold standard treatment in this situation. Reinfection is the main cause of failure in pulpectomy. The application of regenerative endodontic therapy in mature teeth has the rationale of restoring dental-pulp-like tissue and preventing reinfection. The current study was designed to clinically and radiographically assess regenerative endodontics therapy in necrotic primary molars in comparison to zinc oxide eugenol (ZOE) pulpectomy. A double-blinded randomized controlled trial with three parallel arms and a 1:1:1 allocation ratio was conducted. A total of 54 necrotic primary molars in 39 healthy children aged 4-7 years old were randomly allocated as follows group I-control group, in which ZOE pulpectomy was performed. Group II and III-experimental groups, in which regenerative endodontic therapy (RET) was performed. Modified triple antibiotic paste (mTAP) and Metapex™ were used as intracanal medicaments in groups II and III, respectively. Clinical and radiographic assessments were recorded at baseline, 6 and 12 months. Chi-squared and Fisher's exact tests were used to compare the qualitative data, while Friedman's test was used to study the changes by time within each group. Nonstatistically significant differences were reported between the three groups at the 6 and 12 months follow-ups regarding the clinical or radiographic assessment (p-value = 0.327 and effect size = 0.22), (p-value = 0.055 and effect size = 0.118), respectively. Regenerative endodontic therapy (RET) yielded comparable results to pulpectomy. However, the use of 5 mg/mL mTAP in RET represented the highest level of clinical as well as radiographic insignificant failure. Regenerative endodontic therapy (RET) provides an acceptable biological alternative to pulpectomy. The protocol was registered at ClinicalTrial.gov with the registration number (NCT04190914). 12/5/2019. Abdelmoneim DD, Abdelaziz AM, Allam GG, et al. A 1-year Clinical and Radiographic Assessment of Regenerative Endodontic Therapy for Necrotic Primary Molars: A Randomized controlled Trial. Int J Clin Pediatr Dent 2023;16(2):295-301.

Regenerative endodontic therapy in mature teeth with necrotic pulp and apical periodontitis using two disinfection protocols

ObjectiveThis study compared the effect of diode laser (DL) 980 nm and double antibiotic paste (DAP) on response of mature teeth with necrotic pulp and apical periodontitis to regenerative endodontic therapy in a dog model.MethodsPulp necrosis and periapical pathosis were induced in 40 mature double rooted premolars in four 2-year-old mongrel dogs. These teeth were randomly divided according to disinfection protocol into four equal groups (10 teeth each/20 roots), group I: DAP; group II: DL980 nm; group III: positive control (without treatment) and group IV: negative control (untouched teeth). These groups were further subdivided into 2 subgroups (5 teeth each/10 roots) according to evaluation period, subgroup (A): one month and subgroup (B): three months. Revascularization techniques were performed using bleeding induction and application of platelet rich fibrin (PRF). The coronal cavities were sealed with mineral trioxide aggregate (MTA) and glass ionomer cement. The inflammatory response, vital tissue in-growth, new hard tissue formation and bone resorption were assessed. Statistical analysis was done utilizing ANOVA, Tukey’s post hoc and paired t tests.ResultsIn both subgroups, there were no significant differences between DAP and DL980 in terms of inflammatory cell count, vital tissue in-growth, new hard tissue formation and bone resorption (P ≤ 0.05).ConclusionDiode laser 980 nm can alternate DAP as a disinfection method of the root canal during RET for mature necrotic teeth, therefore it may accelerate regenerative endodontic therapy for both the patient and dentist and allows for RET in a single appointment.

Influence of Ascorbic Acid as a Growth and Differentiation Factor on Dental Stem Cells Used in Regenerative Endodontic Therapies.

Vitamin C is one of the major extracellular nonenzymatic antioxidants involved in the biosynthesis of collagen. It promotes the growth of fibroblasts, wound healing processes, and enhances the survival and differentiation of osteoblasts. The potential effects of ascorbic acid on human dental pulp cells (DPC) and the cells of the apical papilla (CAP) used in actual regenerative endodontic procedures remain largely unknown. In this study, we investigated the possible employment of ascorbic acid in the differentiation and regenerative therapies of DPC and CAP. Nine extracted human wisdom teeth were selected for this study. Subpopulations of stem cells within DPC and CAP were sorted with the mesenchymal stem cell marker STRO-1, followed by treatments with different concentrations (0 mM, 0.1 mM, 0.5 mM, and 1.0 mM) of ascorbic acid (AA), RT-PCR, and Western blot analysis. FACS analysis revealed the presence of cell subpopulations characterized by a strong expression of mesenchymal stem cell marker STRO-1 and dental stem cell markers CD105, CD44, CD146, CD90, and CD29. Treatment of the cells with defined amounts of AA revealed a markedly increased expression of proliferation marker Ki-67, especially in the concentration range between 0.1 mM and 0.5 mM. Further investigations demonstrated that treatment with AA led to significantly increased expression of common stem cell markers OCT4, Nanog, and Sox2. The most potent proliferative and expressional effects of AA were observed in the concentration of 0.1 mM. AA might be a novel and potent growth promoter of human dental cells. Increasing the properties of human dental pulp cells and the cells of the apical papilla using AA could be a useful factor for further clinical developments of regenerative endodontic procedures.

Comparison of various methods for removing double antibiotic paste from root canal walls during regenerative endodontic therapy

ABSTRACT Aim: This study investigated the efficacy of Endoactivator, Pro-agitator tip system (PATS) Vario, BF brush, and dual side-vented needle irrigation to remove double antibiotic paste (DAP) from the root canal. Methods: Biomechanical preparation till size #25 (F2) was carried out utilizing the Protaper Universal System on 92 extracted teeth with single root and root canal. All the canals were filled with DAP for 21 days, and the roots were split into two halves (n = 20) and divided into four groups randomly based on the irrigation method, using either dual side-vented needle irrigation, BF brush, Endoactivator, or PATS Vario. Under a stereomicroscope, the quantity of medication still present at every root half was assessed using a four-grade scoring system. Results: PATS Vario (0.46 ± 0.50) followed by Endoactivator (0.46 ± 0.52) groups were substantially more effective at eliminating DAP from the root canal than BF brush groups (0.98 ± 0.58) and dual side-vented irrigation tips (2.29 ± 0.53) (P &lt; 0.05) However, none of the methods succeeded in entirely removing antibiotic paste from canal walls. Conclusion: PATS Vario Group was more efficient than Endoactivator at eliminating DAP from root canal walls, but the difference was not statistically significant (P &gt; 0.05).

Comparative outcomes of platelet concentrates and blood clot scaffolds for regenerative endodontic procedures: A systematic review of randomized controlled clinical trials.

The main objective of this systematic review is to evaluate the effectiveness of platelet concentrates -Platelet-rich plasma (PRP) or Fibrin-rich plasma (PRF)- compared with blood clot (BC) as scaffolds for maturogenesis, in patients with immature permanent teeth with or without AP, in terms of the criteria for pulp revascularization success. We reviewed randomized controlled clinical trials comparing regenerative endodontic therapies (maturogenesis) based on PRP or PRF versus the conventional BC approach, in necrotic teeth with or without apical periodontitis (AP) under clinical and radiographic criteria. We performed a strategic search in MEDLINE (PUBMED), EMBASE, and ISI Web of Science from inception to October 2022. This systematic review of the literature was developed following the Cochrane Collaboration and PRISMA statement recommendations. We used the Cochrane risk of bias tool v2 to assess the included studies' quality. We performed a qualitative synthesis of the evidence. Ten randomized controlled clinical trials were included in this systematic review. Analyses of these studies suggest that maturogenesis is a successful therapy regardless of the method employed. However, further research should be conducted with more suitable research methodologies and more homogenous data for meta-analysis. Results from this systematic review suggest that BC maturogenesis approaches yield similar clinical and radiographic outcomes when compared to Platelet-concentrates based therapies (PRP and PRF). Key words:Maturogenesis, Revascularization, Platelet-rich plasma, Fibrin-rich plasma, blood clot, systematic review.

The Effect of Etiology on the Function of Hertwig\'s Epithelial Root Sheath in Regenerative Endodontic Procedures—A Review of Literature

AbstractThe management of nonvital immature permanent teeth poses quite a challenge. The apexification procedure is in use for long-term now but the treated teeth are more prone to fracture questioning the long-term prognosis of this technique. The introduction of regenerative procedures for the treatment of these teeth is quite favorable; however, despite the increasing use of regenerative endodontic therapy procedures, inconsistent results are seen in the root development. Conservation of Hertwig's epithelial root sheath may have a prime role and selecting the cases with viable root sheath may impact on the consistent positive results treated with regenerative procedures. This article aims to look at the database to find the role of etiology and its implication on Hertwig's epithelial root sheath in the outcome of regenerative endodontics.

Regenerative endodontic therapy for external inflammatory lateral resorption following traumatic dental injuries: Evidence assessment of best practices.

External inflammatory lateral resorption (EILR) following dental trauma is a severe complication that can lead to significant root loss and tooth extraction. The aim of this project was to review current evidence in the literature on regenerative endodontic therapy (RET) for EILR following traumatic injuries and assess the best treatment practices. Publications appearing in PubMed, from January 1, 2001 to January 9, 2022 were studied. Inclusion criteria were: (a) Publications in English; (b) Publications on RET and EILR; (c) Teeth subjected to dental trauma; and (d) Presence of intracanal bleeding and blood clots. Exclusion criteria were: (a) Conference proceedings; (b) Lectures; (c) Abstracts; and (d) Letters to editor; (e) Non-English publications. 355 publications were analysed. Nine met all inclusion criteria. In 10 (58.8%) teeth, triple antibiotic paste was used for an average of 26 days. Double antibiotic paste was used in 3 (17.6%) teeth for an average of 14 days. In 3 (17.6%) cases, calcium hydroxide (Ca(OH)2 ) was used for 14 days and negative pressure irrigation was applied once on 1 (6%) tooth. Using RET to treat EILR has some advantages compared to long term CA(OH)2 dressing. RET requires shorter dressing time compared to CA(OH)2 . This can significantly improve patient compliance. Additionally, in immature teeth, RET helps to arrest root resorption leading to continued root maturogenesis and revascularization. It is recommended that a meticulous follow-up should be conducted when RET is performed to assure early detection of treatment failure. RET appears to be a good treatment modality producing biologic repair and improving prognosis in cases of EILR in post-traumatic tooth/pulp injuries. The key limitation of this study is that all publications included were either case reports or case series that usually tend to report successful outcome.

The Four Pillars for Successful Regenerative Therapy in Endodontics: Stem Cells, Biomaterials, Growth Factors, and Their Synergistic Interactions.

Endodontics has made significant progress in regenerative approaches in recent years, thanks to advances in biologically based procedures or regenerative endodontic therapy (RET). In recent years, our profession has witnessed a clear conceptual shift in this therapy. RET was initially based on a blood clot induced by apical bleeding without harvesting the patient's cells or cell-free RET. Later, the RET encompassed the three principles of tissue engineering, stromal/stem cells, scaffolds, and growth factors, aiming for the regeneration of a functional dentin pulp complex. The regenerated dental pulp will recover the protective mechanisms including innate immunity, tertiary dentin formation, and pain sensitivity. This comprehensive review covers the basic knowledge and practical information for translational applications of stem cell-based RET and tissue engineering procedures for the regeneration of dental pulp. It will also provide overall information on the emerging technologies in biological and synthetic matrices, biomaterials, and signaling molecules, recent advances in stem cell therapy, and updated experimental results. This review brings useful and timely clinical evidence for practitioners to understand the challenges faced for a successful cell-based RET and the importance of preserving or reestablishing tooth vitality. The clinical translation of these current bioengineering approaches will undoubtedly be beneficial to the future practice of endodontics.

Endodontic and surgical treatment of chronic apical periodontitis: a randomized clinical study

The development of regenerative endodontic therapy offers new opportunities for faster tooth recovery in chronic apical periodontitis. This study aimed to use three different surgical protocols to compare the results (filling the apical lesion with bone tissue over 6 months) of treatment in patients with chronic apical periodontitis. This study included 23 patients and 30 teeth with chronic apical periodontitis. The patients were divided into three groups: (1) Endodontic treatment and apical osteotomy without filling; (2) Endodontic treatment and apical osteotomy with the placement of blood concentrate according to the advanced platelet-rich fibrin A-PRF + protocol; (3) Endodontic treatment and apical osteotomy with the placement of blood concentrate according to the ‘sticky bone’ and A-PRF + protocols with allograft. The results were reported after 6 months using cone-beam computed tomography. The results showed a statistically significant difference (Mann–Whitney U test) in the filling of the bone defect in the healing process between the first group (average rank 31.490) and the second group (average rank 96.015), as well as between the first group (average rank 31.490) and the third group (average rank 91.765). No significant difference was found in the filling of the bone defects between the second and third groups. We show that placement of A-PRF + blood concentrate alone or combined with alloplastic graft after classical apical osteotomy of teeth with chronic apical periodontitis leads to a size reduction of the bone defect with 95.25% for group 2 and 90.80% for group 3 after 6 months.

Clinical Outcome and Comparison of Regenerative and Apexification Intervention in Young Immature Necrotic Teeth-A Systematic Review and Meta-Analysis.

This systematic review aimed to evaluate interventions individually and compare the clinical outcome of young, immature teeth treated with regenerative endodontic therapy (RET) and apexification procedure. The protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews), bearing the registration number CRD42021230284. A bibliographic search in the biomedical databases was conducted in four databases—PubMed, CENTRAL, EMBASE and ProQuest—using searching keywords and was limited to studies published between January 2000 and April 2022 in English. The search was supplemented by manual searching, citation screening and scanning of all reference lists of selected paper. The study selection criteria were randomized clinical trial, prospective clinical studies and observational studies. The search found 32 eligible articles, which were included in the study. The quality assessment of the studies was performed using the Cochrane risk of bias tool for randomized control trials and non-randomized clinical studies. The meta-analysis was performed using Review Manager software (REVMAN, version 5). The results indicated that a clinicians’ MTA apexification procedure was more successful compared to calcium hydroxide. In RET, apical closure and overall success rate is statistically same for both apical platelet concentrates (APCs) and blood clots (BC). Both interventions have similar survival rates; however, RET should be preferred in cases where the root development is severely deficient, there is insufficient dentine and the tooth’s prognosis is hopeless even with an apexification procedure.