Regenerative Endodontics Research Articles (Page 1)

Regenerative endodontics (RE) is a biologically based procedure designed to replace damaged dental structures, including dentin and root structures, and cells of the pulp-dentin complex. It is the first-line treatment for patients with immature permanent teeth (IPT) that have lost vitality due to dentoalveolar trauma (DAT), caries, or developmental anomalies such as dens evaginatus (DE). Beyond resolving clinical signs and symptoms, RE allows for continued root development, substantially improving the long-term prognosis of these cases. Here, we present a clinical case of a 12-year-old female patient who, as a result of dentoalveolar trauma, exhibits asymptomatic apical periodontitis of tooth 1.1 and chronic apical abscess of tooth 2.1 in IPT. Both teeth were treated with regenerative endodontics, achieving successful RE in tooth 2.1 and inducing apical closure with Biodentine in tooth 1.1. In addition, we conducted a bioinformatic analysis to identify key genes associated with the success of post-trauma RE, providing a more complete and mechanistic understanding of the factors determining treatment success. In conclusion, the success of RE procedures in IPT may be conditioned by the type of DAT suffered by the tooth. Moreover, incorporating bioinformatic analysis introduces an innovative approach to unravel the molecular mechanisms involved in post-trauma dental regeneration.

To reassess the success rate of vital pulp therapy (VPT) in dogs and evaluate the impact of patient age and pulp exposure duration on outcomes. The University of Wisconsin Veterinary Care medical records database was searched for dogs undergoing VPT from January 2000. Patient age, pulp exposure duration, and other variables were recorded. Radiographs taken before, immediately after, and at the last follow-up were evaluated. Outcomes were categorized as successful, having no evidence of failure, or failure. Of 219 VPT cases, 48 dogs with 79 teeth met the inclusion criteria. The VPT success rate was 80% (63 of 79). No significant correlation was found between age and success. Longer exposure (> 24 hours) was linked to longer time to failure, while shorter exposure (< 24 hours) had a shorter time to failure, compared to immediate treatment. Deep penetration of pulp dressing significantly increased failure odds. VPT remains a viable alternative to root canal therapy for managing pulp exposure in dogs, with an 80% success rate. While age and exposure duration did not significantly impact outcomes, pulp dressing depth and treatment indication (eg, malocclusion vs complicated crown fracture) did. This study updates the success rate of VPT in dogs and examines factors influencing outcomes with current standards. Potential advancements in biomaterials and regenerative endodontics to improve future success are also discussed.

Enhanced neurogenic differentiation of human dental pulp stem cells via BDNF-loaded oxidized alginate hydrogel.

INTRODUCTION. Dental pulp stem cells (DPSCs) are of interest in regenerative endodontics due to their multipotency. Mineral trioxide aggregate (MTA) is highly sought after due to its biocompatibility, but the limitations of long setting time and poor handling have created interest in newer products such as Baghdadite. To evaluate the biocompatibility and osteogenic potential of Baghdadite, MTA, and their combination on DPSCs using MTT and Alizarin Red assay.MATERIALS AND METHODS. DPSCs were cultured and characterized by flow cytometry and CFU assays. Experimental groups (MTA, Baghdadite, MTA+Baghdadite) were exposed to cytotoxicity test (MTT assay) and mineralization test (Alizarin Red staining).RESULTS. Cell viability of all the groups was higher than control. Combination group showed maximum viability (mean OD: 0.4066) than Baghdadite (0.3975) and MTA (0.3563). Alizarin Red staining showed the maximum mineralization in combination group (mean OD: 1.7069) than MTA (0.5788) and Baghdadite (0.4020).CONCLUSIONS. The association of MTA and Baghdadite showed improved biocompatibility and osteogenic ability, which is promising for application as a pulp-capping agent in regenerative endodontics.

ABSTRACT Background: Traumatic dental injuries (TDIs) often compromise the dentin-pulp complex, necessitating innovative therapeutic approaches. Stem cell therapy has emerged as a promising solution for regenerative endodontics. Objective: This research investigates the application of stem cell therapy in regenerating dentin for patients with TDIs by using a retrospective analysis of clinical outcomes. Methods: A retrospective data analysis was performed on 120 cases involving TDIs treated with stem cell-based interventions. Key parameters included patient demographics, clinical outcomes, and histological findings. Statistical significance was assessed using a P value of &lt;0.05. Results: Significant improvement in dentin regeneration was observed in 85% of cases treated with stem cell therapy. Histological findings confirmed the formation of tubular dentin in 75% of cases. Younger patients exhibited superior outcomes compared to older cohorts. Conclusion: Stem cell therapy demonstrates significant potential for regenerating dentin in TDIs. Future studies should explore long-term outcomes and optimization of protocols.

Enhanced regenerative potential of human dental pulp stem cells for the pulp-dentin complex through coculture with iPSC-derived endothelial cells: An in vitro study.

Background: Regenerative dentistry, an emerging branch of dental science, focuses on biological restoration of oral tissues using advanced techniques such as stem cell therapy, tissue engineering, platelet-rich plasma, and guided tissue regeneration. While these approaches are widely recognized internationally, their clinical adoption remains inconsistent in developing countries like Pakistan due to training, cost, and infrastructure limitations. Objective: This study aimed to assess the awareness, knowledge, and adoption of regenerative dentistry among dental students and practitioners in Pakistan and to identify barriers that hinder its integration into routine clinical practice. Methods: A descriptive cross-sectional study was conducted from June to September 2025 using a structured, close-ended online questionnaire distributed among dental professionals and senior undergraduate students across Pakistan. Convenience sampling yielded 204 responses. Data were analyzed using descriptive and inferential statistics in SPSS v27 to determine awareness levels, clinical adoption rates, and perceived barriers. Results: Of 204 respondents, 91.7% were aware of regenerative dentistry, 74.5% understood its scope, and 68.1% were familiar with its clinical applications. The most recognized approaches were stem cell therapy (79.9%) and guided tissue regeneration (73%). However, only 28.9% reported implementing regenerative endodontics and 32.8% used guided tissue regeneration clinically. Key barriers included insufficient training (66.7%), low patient awareness (62.7%), high costs (52.9%), and limited infrastructure (38.2%). Nearly all participants (98%) supported incorporating regenerative dentistry into curricula. Conclusion: Despite widespread awareness of regenerative dentistry among Pakistani dental professionals, clinical adoption remains limited due to educational, economic, and infrastructural constraints. Integrating regenerative concepts into dental curricula, enhancing hands-on training, improving resource availability, and increasing patient awareness are crucial for translating knowledge into clinical practice.

Intracellular Bacteria in Stem Cells of the Apical Papilla: A "Trojan Horse" for Regenerative Endodontic Failure.

The RNA N6-methyladenosine (m6A) modification, catalyzed by methyltransferase-like 3 (METTL3), is a key epigenetic regulator of oral health and disease. This narrative review positions METTL3 as a dual-function master switch in oral biology. It promotes stem cell-driven regeneration but also drives disease progression. Physiologically, METTL3 enhances the odontogenic/osteogenic differentiation of dental pulp stem cells (DPSCs). It stabilizes key transcripts (e.g., lncSNHG7, GDF6, STC1) via m6A modification, activating Wnt/β-catenin signaling to foster dentinogenesis and pulp vitality-key goals in regenerative endodontics. Conversely, METTL3 dysregulation promotes oral diseases. It impairs osteogenesis in periodontal stem cells (BMSCs/PDLSCs) via the IGF2BP1/m6A/RUNX2 and PI3K/AKT pathways, worsening bone loss in periodontitis. In oral squamous cell carcinoma (OSCC), METTL3 acts oncogenic. It stabilizes mRNAs like c-Myc, PD-L1, and BMI1 through reader proteins (YTHDF1/IGF2BPs), driving tumor growth, metastasis, and chemoresistance (e.g., to Cisplatin and Anlotinib). Pharmacological inhibition of METTL3 (e.g., with Allocryptopine or Oxymatrine) shows promise by suppressing OSCC progression and rescuing bone formation. We propose METTL3 as a unifying therapeutic target to advance both regenerative dentistry and precision oncology for oral diseases. Targeting METTL3 epitranscriptomics could transform future oral therapies.

Advances in tissue engineering strategies for periodontal and endodontic regeneration: Current therapies and future trends for disease treatment and tissue repair in the oral cavity.

hDPSC-derived Secretomes Enhance Odontogenic Differentiation and Suppress Inflammation: A Potential Cell-free Approach for Regenerative Endodontics.

Ultrastructural and immunobiological responses of human periodontal ligament stem cells to novel tricalcium silicate sealers.

The management of teeth with open apices, typically resulting from trauma or developmental anomalies, remains a clinical challenge in endodontics. Historically, apexification with long-term calcium hydroxide therapy was the primary approach to induce apical closure. However, this method is associated with extended treatment duration and increased risk of root fracture. Bioceramic materials such as mineral trioxide aggregate (MTA), artificial apical barriers have gained popularity due to their reduced treatment time and favorable sealing properties. More recently, regenerative endodontic procedures (REPs) have emerged as a biologically based alternative aiming to restore the pulp–dentin complex and promote continued root development. This review provides a comprehensive overview of current treatment strategies for immature permanent teeth, comparing traditional apexification with modern regenerative techniques. Clinical indications, protocols, advantages, limitations, and prognosis are discussed in detail to guide evidence-based clinical decision-making.

Regenerative endodontic approaches for immature necrotic permanent teeth must balance biological efficacy, clinical practicality and long-term aesthetic outcomes. This study evaluates a novel regenerative protocol using autologous advanced platelet-rich fibrin plus (A-PRF+) scaffold sealed exclusively with glass ionomer cement (GIC) and compares it to conventional calcium hydroxide apexification used as the control. Twenty-eight patients were prospectively enrolled and followed for 12 months alongside a retrospectively selected historical control group. Outcomes were evaluated through standardised blinded clinical, radiographic and vitality assessments. The A-PRF+ protocol demonstrated significantly faster periapical healing, superior root lengthening, increased dentinal wall thickness and apical closure (p < 0.0001), with excellent aesthetic outcomes and no reported tooth discolouration. Pulpal blood flow measured by laser Doppler flowmetry indicated vitality restoration in 93% of cases. Preliminary linear regression identified treatment duration as a significant predictor of apical closure (p < 0.0001), with possible enhancement by additional patient-specific variables. These findings validate the A-PRF+ protocol as a highly effective, aesthetically favourable and predictable regenerative strategy, establishing a new benchmark for the management of immature necrotic teeth and laying the foundation for personalised predictive endodontic care. Future studies should include multicentre randomised controlled trials to confirm long-term clinical sustainability and generalisability.

BackgroundDental pulp regeneration represents a critical frontier in translational dentistry, with dental pulp stem cells (DPSCs) demonstrating exceptional reparative potential through their multipotent differentiation capacity. While oxygen tension is known to influence cellular physiology, its regulatory mechanisms on DPSC osteo/odontogenic differentiation remain poorly understood.MethodsWe established physiologically relevant oxygen gradients (3%, 5%, 21% O2) to mimic developmental and pathological pulp microenvironments. Cellular proliferation and osteogenic capacity were assessed through flow cytometry, CCK-8 assays, and Live/Dead staining. Differentiation markers (RUNX2, OCN, ALP, DSPP) were quantified via qRT-PCR, immunoblotting, and enzymatic activity assays. Pharmacological inhibition studies using Oltipraz (HIF-1α inhibitor) and Valproic acid (HDAC inhibitor) elucidated pathway interactions. Publicly available transcriptomic datasets were analyzed to identify hypoxia-regulated pathways, and protein interactions were predicted using bioinformatics tools.ResultsModerate hypoxia (5% O2) significantly enhanced DPSC proliferation (p < 0.05 vs. normoxia) and upregulated osteogenic markers at transcriptional (1.8–3.2 fold) and translational levels. Severe hypoxia (3% O2) suppressed both proliferation (p < 0.01) and differentiation markers (0.4–0.7 fold). HIF-1α inhibition reversed 5% O2-mediated osteogenic enhancement (p < 0.01), while HDAC1 blockade with Valproic acid rescued differentiation capacity under 3% O2 (1.5–2.1 fold induction). Mechanistically, HDAC1 appeared to influence HIF-1α protein levels in an oxygen-dependent manner, and its inhibition affected pathways consistent with alterations in chromatin remodeling, influencing VEGFA-mediated osteogenic signaling.ConclusionOur findings establish an oxygen-sensitive HDAC/HIF-1α regulatory axis governing DPSC fate determination. The biphasic response to hypoxia gradients suggests microenvironmental optimization strategies could enhance pulp regenerative outcomes. These insights provide mechanistic foundations for developing HDAC-targeted approaches in endodontic regeneration.

Alginate-Xanthan Nanocomposite Scaffolds Incorporating Copper-Doped Bioactive Glass for Novel Tissue Engineering Potential in Regenerative Endodontics

ObjectiveThis systematic review and meta-analysis aimed to evaluate the efficacy of regenerative endodontic procedures compared with conventional root canal treatment procedures in mature permanent teeth with periapical lesions.MethodsThis systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials that were included in the study compared regenerative endodontic procedures with traditional root canal treatment procedures in mature permanent teeth with irreversible pulpitis. The Risk of Bias 2 tool was used for quality assessment, and the certainty of the evidence was evaluated using the GRADE approach. Meta-analysis was performed using the RevMan Web software, using odds ratios for dichotomous outcomes and mean differences for continuous outcomes, with a random-effects model applied. Heterogeneity was assessed using the I2 statistic, and publication bias was evaluated using funnel plots and Egger's test.ResultsThe analysis included five studies encompassing diverse regenerative strategies. Overall, regenerative endodontic procedures demonstrated comparable or superior clinical and radiographic healing outcomes relative to conventional treatments. Notably, certain regenerative approaches showed greater potential for restoring pulp vitality and reducing early postoperative pain. However, the quality of evidence was moderate, constrained by small sample sizes, methodological heterogeneity, and blinding challenges.ConclusionCurrent evidence suggests that regenerative endodontic procedures are promising alternatives to conventional root canal treatment procedures for mature teeth with periapical lesions. Despite these encouraging findings, further high-quality, multicenter trials with standardized protocols and extended follow-up periods are necessary to confirm the results and establish the long-term benefits and cost-effectiveness of regenerative endodontics.

Injectable laponite nanocomposite hydrogel with synergistic antibacterial and odontogenic activity for endodontic regeneration.

Although regenerative endodontics has advanced in recent years, the influence of pre-operative factors on treatment outcomes remains poorly understood. To evaluate the effect of pre-operative factors-including age, gender, tooth type, aetiology of pulp necrosis, stage of root development, clinical signs/symptoms and periradicular status-on the treatment outcomes of regenerative endodontic procedures (REPs) in immature permanent teeth. A literature search was conducted on six electronic databases and grey literature to identify studies investigating the effect of pre-operative factors on REP outcomes. The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk-of-Bias 2 tool for randomised clinical trials (RCTs). Meta-analyses of proportions were conducted to estimate pooled rates for the outcomes 'clinical and radiographic healing', 'root development' and 'apical closure' across different pre-operative factors. Associations between these factors and treatment outcomes were assessed through meta-analyses of effect sizes. The certainty of evidence was evaluated using the GRADE approach. Twenty studies were included, comprising 13 observational studies and seven RCTs. Most studies presented a moderate to high risk of bias. The pooled success rate for clinical and radiographic healing exceeded 81% across all pre-operative factors. Moreover, root development was achieved in 52%-95% of cases, whereas complete apical closure ranged from 32% to 91%. No significant association was found between pre-operative factors and clinical and radiographic healing. It was found that teeth with pulp necrosis due to trauma presented 3.59 times higher relative risk of root development failure compared to those with necrosis due to anatomic anomaly (RR = 3.59, 95% CI 1.21-10.67, p = 0.02). Incisors presented 1.90 times higher relative risk of root development failure (RR = 1.90, 95% CI: 1.37-2.63, p < 0.01) and 1.98 times higher relative risk of incomplete apical closure (RR = 1.98, 95% CI: 1.34-3.13, p = 0.02) compared to premolars. The presence of an apical lesion increased the relative risk of root development failure by 2.55 times (RR = 2.55, 95% CI: 1.63-4.86, p = 0.01). The certainty of evidence was rated as very low. Pre-operative factors were not significantly associated with clinical and radiographic healing in REPs. However, trauma-related pulp necrosis, tooth type (incisors) and the presence of apical lesions were associated with an increased risk of root development failure. These findings should be interpreted with caution due to between-study heterogeneity, the moderate to high risk of bias and the very low certainty of the evidence.

Although regenerative endodontics demonstrate promise for dental pulp regeneration, chronic inflammation often hinders the success. This study aims to explore the mechanism whereby lipopolysaccharide (LPS) induces dental pulp regeneration failure. Transcriptomic profiling of LPS-stimulated dental pulp stem cells (DPSCs) reveals dysregulated cation homeostasis and increased magnesium (Mg2⁺) transmembrane transport. Mechanistically, LPS is observed to activate the transcription factor signal transducer and activator of transcription 5A (STAT5A), which binds to the solute carrier family 41 member 1 (SLC41A1) promoter, thereby upregulating the Mg2⁺ efflux transporter and depleting intracellular Mg2⁺ levels. Mg2⁺ efflux destabilizes the mitochondrial permeability transition pore (mPTP), thus facilitating its opening via the interaction of oligomycin sensitivity-conferring protein (OSCP) and cyclophilin D (CypD), which releases reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) and exacerbates oxidative stress. The released mtDNA activates the absent in melanoma 2 (AIM2) inflammasome, thereby amplifying gasdermin D (GSDMD)-mediated pyroptosis. Exogenous supplementation with Mg2⁺ restores intracellular Mg2⁺ homeostasis, suppresses mPTP opening, and reduces mtDNA and ROS leakage, thereby rescuing DPSCs viability and differentiation capacity. This study identifies SLC41A1-mediated Mg2⁺ dysregulation as a pivotal driver of LPS-induced mitochondrial damage and demonstrates that Mg2⁺ replenishment is a therapeutic strategy to counteract inflammation-driven regenerative failure.