A 12-month randomized controlled trial to assess the efficacy of revitalization of retreated mature incisors with periapical radiolucency in adolescents.

The use of regenrative endodontics is restoring the health status of the root canals of retreated mature teeth is a novel approach. Therefore, the current trial aimed to compare the effectiveness of regenerative endodontic procedures (REPs) to non-surgical root canal retreatment (NS-RCR) in reducing periapical radiolucency over one year for the retreatment of mature incisors with periapical periodontitis. The secondary purpose was to assess clinical success and regain pulp sensibility. A parallel randomized controlled trial, 66 mature incisors with periapical radiolucencies were randomly divided into two equal groups and retreated with either REPs or NS-RCR. At baseline and after 6 and 12 months, teeth were assessed clinically and radiographically using a periapical index (PAI). The Mann-Whitney test was used to analyze nonparametric PAI scores. The Electric pulp test readings were analyzed using the repeated measure analysis of variance (ANOVA). Over the follow-up intervals, there was no significant intergroup difference in the PAI medians, the majority of the teeth displayed a reduction in periapical radiolucency. At the end of the follow-up period, the clinical successes for the REP and NS-RCR groups were 93.9% and 97%, respectively (p = 0.555). Positive pulp sensibility was recorded in 54.54% of cases in the REPs after 12 months. Both approaches showed a comparable diminishing of periapical radiolucencies and equivalent clinical results. A conventional, non-surgical endodontic retreatment may not always be necessary.

Regenerative potential of mesoporous silica nanoparticles scaffold on dental pulp and root maturation in immature dog's teeth: a histologic and radiographic study.

OBJECTIVE: To evaluate histologically and radiographically the potential of dog's immature roots with apical periodontitis to regenerate after regenerative endodontic treatment using mesoporous silica nanoparticles (MSNs) with/without bone morphogenic protein (BMP-2) as scaffolds. METHODS: In 4 mongrel dogs, 56 immature teeth with 96 roots were infected, resulting in necrotic pulps and periapical pathosis. According to the evaluation time (Group I = 30 days and Group II = 90 days), 90 roots were divided into two equal groups (45 roots each) and 6 roots used to replace any lost root during the procedure. The two main groups were further divided according to treatment protocol into 5 subgroups (9 roots each): blood clot (BC subgroup), mesoporous silica nanoparticles scaffold only (MSNs subgroup), mesoporous silica nanoparticles impregnated with BMP2 (MSNs + BMP2 subgroup), infected teeth without treatment (+ ve control subgroup) and normal untouched teeth (-ve control subgroup). All teeth surfaces were coated with Tincture iodine and calcium hydroxide was applied prior to treatment protocols. Then, teeth were restored with glass ionomer filling to seal the remaining part of the access cavity. Radiography evaluation of the increase in root length, root thickness and occurrence of apical closure were performed. Following the sacrifice of the two dogs at each time of evaluation, histopathological analysis was performed and included the inflammatory cells count, bone resorption, tissue ingrowth, deposition of hard tissue, and closure of the apical part. All data were statistically analyzed. RESULTS: Compared to BC subgroup, MSNs and MSNs + BMP-2 subgroups exhibited significant higher increase in root length and thickness as well as higher vital tissue in-growth and new hard tissue formation in group II (P < 0.05). MSNs + BMP-2 subgroup had significant higher increase in root length and thickness as well as significant lower inflammatory cell count than MSNs subgroup in both groups (P < 0.05). There were no significant differences between MSNs and MSNs + BMP-2 subgroups regarding new hard tissue formation in both groups and apical closure in group I (P > 0.05). CONCLUSION: MSNs with/without BMP-2 scaffolds enabled the continuing growth of roots in immature teeth with necrotic pulps and periapical pathosis. Addition of BMP-2 to MSNs scaffold improved its outcome in regenerative endodontics. CLINICAL RELEVANCE: MSNs with/without BMP-2 scaffolds may alternate blood clot for regenerative endodontic treatment of immature teeth with necrotic pulps.

Regenerative endodontic treatment of necrotic permanent teeth with pre-eruptive intracoronal radiolucency: a case report.

Pre-eruptive intracoronal radiolucency is a rare dental anomaly with unclear aetiology, generally asymptomatic and diagnosed through routine radiographs. Failure to diagnose and treat it early can lead to rapid pulp damage, potentially compromising root development. The presented clinical report describes a mandibular second premolar with pre-eruptive intracoronal radiolucency that caused early pulp necrosis with arrest of root formation and emphasises the endodontic management using regenerative endodontic therapy.

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

OBJECTIVE: 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). METHODOLOGY: 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. RESULTS: 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). CONCLUSION: 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.

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.

Regenerative Endodontic Procedure on an Immature Necrotic Molar: A Case Report with a 5-Year Review.

BACKGROUND The regenerative endodontic procedure (REP) for managing necrotic immature permanent teeth has the advantage of promoting root growth over the traditionally used apexification techniques. However, there is limited evidence on the long-term outcome of standardized REPs performed on immature molars. This case report presents the 5-year clinical and radiographic outcomes of REP performed on an immature mandibular first molar. CASE REPORT A healthy 7-year-old girl with a carious right mandibular first molar was referred to the endodontic clinic for evaluation and treatment. Clinical examination showed large occlusal caries, no tenderness to palpation and percussion tests, and no response to cold and electric pulp tests. Radiographic examination showed deep caries, apical radiolucency related to the open apices, and wide root canal space. Accordingly, the tooth was diagnosed with necrotic pulp and asymptomatic apical periodontitis. The REP was performed following the American Association of Endodontics guidelines, which comprise minimal instrumentation, disinfection with sodium hypochlorite irrigant, use of triple antibiotic paste, induced intracanal bleeding, and application of a coronal mineral trioxide aggregate plug. The patient missed the scheduled follow-up appointments but presented at the clinic 5 years later with an asymptomatic tooth. Clinical and radiographic examination revealed no tenderness to percussion and palpation test, no response to cold test, positive response to electric pulp test, apical healing, apical closure, root lengthening, and canal wall thickening and calcification. CONCLUSIONS While true pulp regeneration is unachievable, the REP, following the current protocol, is clinically successful in achieving root maturation and tooth retention.

Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration.

Dental pulp is the only soft tissue in the tooth which plays a crucial role in maintaining intrinsic multi-functional behaviors of the dentin-pulp complex. Nevertheless, the restoration of fully functional pulps after pulpitis or pulp necrosis, termed endodontic regeneration, remained a major challenge for decades. Therefore, a bioactive and in-situ injectable biomaterial is highly desired for tissue-engineered pulp regeneration. Herein, a decellularized matrix hydrogel derived from porcine dental pulps (pDDPM-G) was prepared and characterized through systematic comparison against the porcine decellularized nerve matrix hydrogel (pDNM-G). The pDDPM-G not only exhibited superior capabilities in facilitating multi-directional differentiation of dental pulp stem cells (DPSCs) during 3D culture, but also promoted regeneration of pulp-like tissues after DPSCs encapsulation and transplantation. Further comparative proteomic and transcriptome analyses revealed the differential compositions and potential mechanisms that endow the pDDPM-G with highly tissue-specific properties. Finally, it was realized that the abundant tenascin C (TNC) in pDDPM served as key factor responsible for the activation of Notch signaling cascades and promoted DPSCs odontoblastic differentiation. Overall, it is believed that pDDPM-G is a sort of multi-functional and tissue-specific hydrogel-based material that holds great promise in endodontic regeneration and clinical translation. STATEMENT OF SIGNIFICANCE: Functional hydrogel-based biomaterials are highly desirable for endodontic regeneration treatments. Decellularized extracellular matrix (dECM) preserves most extracellular matrix components of its native tissue, exhibiting unique advantages in promoting tissue regeneration and functional restoration. In this study, we prepared a porcine dental pulp-derived dECM hydrogel (pDDPM-G), which exhibited superior performance in promoting odontogenesis, angiogenesis, and neurogenesis of the regenerating pulp-like tissue, further showed its tissue-specificity compared to the peripheral nerve-derived dECM hydrogel. In-depth proteomic and transcriptomic analyses revealed that the activation of tenascin C-Notch axis played an important role in facilitating odontogenic regeneration. This biomaterial-based study validated the great potential of the dental pulp-specific pDDPM-G for clinical applications, and provides a springboard for research strategies in ECM-related regenerative medicine.

Deciduous pulp tissue implantation into the root canal of mandibular incisor resulted in pulp revascularization: a case report with a 5-year follow-up.

To explore a new method to implant deciduous tooth pulp into the canal of young permanent teeth with necrotic pulps and apical periodontitis for the regenerative endodontic treatment of tooth no: 41 in a 7-year-old male. Briefly, 1.5% Sodium Hypochlorite (NaOCl) irrigation and calcium hydroxide-iodoform paste were used as root canal disinfectant at the first visit. After 2 weeks, the intracanal medication was removed, and the root canal was slowly rinsed with 17% Ethylene Diamine Tetraacetic Acid (EDTA), followed by flushing with 20 mL saline and then drying with paper points. Tooth no: 72 was extracted, and its pulp was extracted and subsequently implanted into the disinfected root canal along with induced apical bleeding. Calcium hydroxide iodoform paste was gently placed over the bleeding clot, and after forming a mineral trioxide aggregate (MTA) coronal barrier, the accessed cavities were restored using Z350 resin composite. The root developments were evaluated via radiographic imaging at 6 months, 1 year and 5 years after treatment. Imaging and clinical analysis showed closure of the apical foramen, thickening of the root canal wall, and satisfactory root length growth. Autologous transplantation might be useful to regenerate dental pulp in necrotic young permanent teeth.

GelMA-based hydrogel biomaterial scaffold: A versatile platform for regenerative endodontics.

Endodontic therapy, while generally successful, is primarily limited to mature teeth, hence the pressing need to explore regenerative approaches. Gelatin methacryloyl (GelMA) hydrogels have emerged as pivotal biomaterials, promising a bright future for dental pulp regeneration. Despite advancements in tissue engineering and biomaterials, achieving true pulp tissue regeneration remains a formidable task. GelMA stands out for its injectability, rapid gelation, and excellent biocompatibility, serving as the cornerstone of scaffold materials. In the pursuit of dental pulp regeneration, GelMA holds significant potential, facilitating the delivery of stem cells, growth factors, and other vital substances crucial for tissue repair. Presently, in the field of dental pulp regeneration, researchers have been diligently utilizing GelMA hydrogels as engineering scaffolds to transport various effective substances to promote pulp regeneration. However, existing research is relatively scattered and lacks comprehensive reviews and summaries. Therefore, the primary objective of this article is to elucidate the application of GelMA hydrogels as regenerative scaffolds in this field, thereby providing clear direction for future researchers. Additionally, this article provides a comprehensive discussion on the synthesis, characterization, and application of GelMA hydrogels in root canal therapy regeneration. Furthermore, it offers new application strategies and profound insights into future challenges, such as optimizing GelMA formulations to mimic the complex microenvironment of pulp tissue and enhancing its integration with host tissues.

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.

Can a dentin bonding agent prevent color change in regenerative endodontic procedures? An in vitro evaluation.

This in vitro study aimed to determine the efficacy of dentin bonding agents in preventing color changes following Regenerative Endodontic Procedures. One hundred twenty bovine incisors were endodontically prepared and randomly assigned to a two main factors design: application of a dentin bonding agent (Scotchbond Adper, 3M ESPE, St Paul, MN, USA) in the pulp chamber (Group 1, n=60) versus no bonding intervention (Group 2, n=60), and five levels of intracanal medication (n=12/subgroup): Triple antibiotic paste (TAP), double antibiotic paste (DAB), calcium hydroxide (CH), modified triple antibiotic paste (TAPM), and Control (CTL). Color changes were measured over 28 days at multiple time points (1, 3, 7, 14, 21, and 28 days) using the CIEDE2000 formula to calculate the color difference (ΔE00) from baseline (T0). The ΔE00 quantifies the perceptible color difference between the initial and final tooth color, with lower values indicating less discoloration. The results were analyzed using repeated measures ANOVA-2 and post-hoc Holm-Sidak tests. The TAP subgroups, both with and without the bonding agent, exhibited the highest color variation. However, a pulp chamber seal with a bonding agent showed a protective effect against discoloration compared to no seal, even though complete prevention was not achieved. All groups demonstrated ΔE00 values beyond acceptable interpretation thresholds for clinical application, primarily driven by a reduction in lightness (L*) and a decrease in redness (a* value, shifting towards green). In conclusion, while the pulp chamber seal with a bonding agent mitigated TAP-induced discoloration, it did not eliminate it.

Enhancing Antibiotic Efficacy in Regenerative Endodontics by Improving Biofilm Susceptibility.

INTRODUCTION: Various strategies have been researched to enhance the susceptibility of biofilms, given their tolerance to antibiotics. This study evaluated the effect of the anti-microbial peptide nisin in association with antibiotics used in regenerative endodontics, exploring different treatment times and biofilm growth conditions. METHODS: A mixture of 10 bacterial species was cultivated on dentin specimens anaerobically for 21 days. Biofilms were treated with 1 mL of high-purity nisin Z (nisin ZP, 200 µg/mL) and a triple antibiotic mixture (TAP: ciprofloxacin + metronidazole + minocycline, 5 mg/mL), alone or in combination. The effectiveness of antimicrobial agents was assessed after 1 and 7 days. During the 7-day period, biofilms were treated under 2 conditions: a single dose in a nutrient-depleted setting (ie, no replenishment of growth medium) and multiple doses in a nutrient-rich environment (ie, renewal of medium and antimicrobial agents every 48 h). After treatments, biofilm cells were dispersed, and total colony-forming units were counted. RESULTS: After 1 d-treatment, nisin ZP + TAP resulted in 2-log cell reduction compared to TAP alone (P < .05). After 7 d-treatment with a single dose, nisin ZP + TAP and TAP reduced bacteria to nonculturable levels (P < .05), whereas repeated antimicrobial doses did not eliminate bacteria in a nutrient-rich environment. No bacterial reduction was observed with nisin ZP alone in any treatment time. CONCLUSIONS: The additional use of nisin improved the TAP activity only after a short exposure time. Longer exposure to TAP or nisin + TAP in a nutrient-deprived environment effectively eliminated biofilms.

Regenerative Endodontic Procedures in Immature Teeth Affected by Regional Odontodysplasia.

INTRODUCTION: Regional odontodysplasia (ROD) is a rare developmental disorder characterized by hypo-mineralization and hypoplasia of enamel and dentin. Symptoms include poorly developed tooth buds, delayed eruption of permanent teeth in affected quadrants, and ghost teeth. The affected teeth often become necrotic due to abnormal enamel and dentin development, making them susceptible to caries and infection. The aim of this case report is to describe the treatment of ROD through pulp revascularization. CASE REPORT: A 13-year-old girl was referred for endodontic treatment. The mandibular left incisors and first premolar, which were affected by regional odontodysplasia, lost their vitality because of the impaired structure of the enamel. Due to the teeth's early developmental stage, a regenerative endodontic treatment was attempted. All 3 teeth were treated using the same protocol following the AAE guidelines. After 4 weeks, treatment of the premolar was completed, whereas the incisor teeth remained symptomatic and were and therefore, intracanal dressing with calcium hydroxide was repeated and left in place for 5 months. Finally, the regenerative procedure was completed, and the crowns were restored. The patient was scheduled for follow-up examinations after 6 months, and then yearly for the next 3 years. After 1 year, the periapical lesion around the central incisor and premolar had resolved, the lesion around the apex of the lateral incisor was healing, and the roots had continued to develop. After 3 years, complete healing and pulp canal obliteration were observed in the central incisor and in the premolar. However, the root of the lateral incisor tooth was split, and it was recommended to extract this tooth. CONCLUSION: The positive outcomes of regenerative endodontics in the central incisor and premolar suggest that revascularization of the pulp may be optional for the treatment of immature necrotic teeth affected by developmental disorders, such as ROD, amelogenesis imperfecta, or dentinogenesis imperfecta.

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.

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

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

Exosomes as Promising Therapeutic Tools for Regenerative Endodontic Therapy.

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

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

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

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

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