Open research questions in Endodontics and Root Canal Treatments

What the literature leaves open

• To strengthen evidence for REP and apexification in imma- ture necrotic teeth, future research should focus on: large multicenter RCTs across diverse populations are needed to improve generalizability.

  Clinical outcomes of regenerative endodontic procedures compared with apexification in young immature necrotic teeth: a systematic review of randomized controlled trials · 2026 · DOI

• One of the limitations of this study was utilizing OPGs for OIEARR evaluation. The lack of a control group without fixed functional appliances was also another limitation of this study.

  Comparison of external apical root resorption and repair levels induced by PowerScope and Forsus fatigue resistant device appliances · 2026 · DOI

• In addition, clinically relevant parameters such as retreatment time, apical debris extrusion [15,26], and the influence of advanced irrigant activation techniques were not investigated in this study. Future studies incorporating more complex root canal anatomies, different bioceramic sealers, volumetric imaging techniques, and clinical outcome measures are warranted to validate and expand upon the present findings.

  Comparative Evaluation of Automated Retreatment Systems for Bioceramic Sealer Removal: An In Vitro Scanning Electron Microscopic Study · 2026 · DOI

• in The failure rate of IANB injection alone indi- cates that it is insufficient to achieve adequate an- esthesia irreversible pulpitis of mandibular molars; therefore, supplemental anesthetic injec- tions are required11,12.

  Anesthetic Efficacy of Inferior Alveolar Nerve Block Combined with Articaine Buccal Infiltration in Molars with Symptomatic Irreversible Pulpitis. · 2026 · DOI

• - Club shape (65 %) and focal (35 %) types observed - Apical deltas in 53.3 % of HC teeth vs 20 % in controls - Frequent constrictions (40 %) and path deviations (46.6 %) - Microscopy showed cementum irregularities and canaliculi linked to apical deltas - Multiple foramina in mild/ moderate forms - Apical obliteration in severe forms - Lateral foramina in focal types - CCH: thick cementum, foraminal depressions - Hypercementosis present in 6.6 % of teeth with chronic pulpitis - Most frequent in 16–35 age group - First molars most commonly affected - Lesions mainly up to 2/3 of root length Table 1: This table presents a summary of experimental and observational studies that investigated various aspects of hypercementosis in teeth. It includes key details and their relevance to the hypothesis regarding the challenges posed by hypercementosis in endodontic treatment. HC: hypercementosis; CBCT: cone beam computed tomography; micro-CT: micro-computed tomography; SEM: scanning electron microscopy; CCH: circular cementum hyperplasia. apical anatomy and foramina, while another was based on histopatho- logical and macroscopic anatomical observations [22]. The case reports and the case series presented a range of endodontic scenarios involving hypercementosed teeth, such as acute apical peri- odontitis [28], asymptomatic apical periodontitis [14,23], failed end- odontic treatments [25], anatomical anomalies [27], and intraoperative diagnostic challenges [26]. The posterior mandibular region was the most frequently affected site, and CBCT imaging was used in several cases to support diagnostic and therapeutic decision-making [14,23,28]. In terms of treatment, both surgical and non-surgical endodontic ap- proaches were discussed, with outcomes varying depending on the severity and morphology of hypercementosis. Tables 1 and 2 provide a detailed synthesis of each study and clinical report, including method- ological or clinical context, findings, endodontic treatment strategies, clinical implications, limitations, and relevance to the research hypothesis. 3.3. Endodontic challenges associated with hypercementosis Hypercementosis presents multiple anatomical and technical chal- lenges that can significantly hinder the success of endodontic treatment. Across the included studies and case reports, the most frequently 71 reported issue was the high morphological variability of the apical third, especially in club-shaped or bulbous root forms [20,21]. The presence of multiple apical foramina, including lateral and accessory canals, was commonly observed, and is associated with difficulty in achieving complete cleaning, shaping, and sealing of the root canal system. In several cases, obliteration or narrowing of the main apical fora- men was reported [14,21,28], preventing proper canal negotiation or instrumentation. Some studies highlighted the displacement of the api- cal foramen from the anatomical apex, or its presence on lateral sur- faces, complicating the determination of the working length [21]. Additionally, excessive cementum apposition may interfere with elec- tronic apex locators and radiographic interpretations [28]. Instrumentation difficulties were frequently cited, especially in teeth with constricted or irregular apical canals [23–25], increasing the risk of procedural errors such as ledging or perforation. In some reports, instrumentation was deemed impossible, leading to the decision to manage the case surgically or conservatively [14]. These findings emphasize the need for adapted endodontic approaches in teeth affected by hypercementosis. C. Lafourcade et al. Japanese Dental Science Review 62 (2026) 68–80 Table 2 Data extraction from clinical case reports.

  Endodontic implications of hypercementosis: A systematic review of anatomical challenges and therapeutic strategies · 2026 · DOI

• The limitations of this study include the inability to assess how long before the patient presented to our institution with symptoms of apical periodontitis, absence of long- term follow-up after treatment, and the fact that symptom- atic teeth were only considered as posterior teeth and could not be classified. 1 3Clinical Oral Investigations (2026) 30:239 Conclusion SAP leads to a decrease in the thickness and stiffness of the masseter muscle on the affected side; this change can be objectively measured using B-mode USG and SWE. Our findings demonstrate that successful RCT initiates a sig- nificant reversal of these biomechanical changes and sup- ports the hypothesis that the adaptation of the masticatory muscles to endodontic pain is reversible. However, the persistence of lower values compared to healthy controls at day 28 suggests that, despite clinical and symptomatic relief, complete physiological restoration of muscle tissue is a progressive process requiring a longer period than the initial healing phase of the periapical tissues. Author contributions Conceptualization: M.E.D., N.Ç.,;Methodology: M.E.D., N.Ç.;Data collection: M.E.D., N.Ç.; Image evaluation and analy- sis: M.E.D.; Statistical analysis: M.E.D.;Writing – original draft: M.E.D., N.Ç.; Writing – review & editing: N.Ç., M.E.D.; Supervision: M.E.D. Funding Open access funding provided by the Scientific and Techno- logical Research Council of Türkiye (TÜBİTAK). There was no fund- ing providers for this study. Data availability It can be obtained from the corresponding author if there is a reasonable reason.

  Ultrasonographic measurement of masseter muscle thickness and elasticity in patients with symptomatic apical periodontitis · 2026 · DOI

• Several limitations should be acknowledged. The retrospec- tive design may introduce selection bias. Although teeth with obvious apical resorption were excluded, the degree of physiological resorption was not quantitatively stratified, nor were age-related differences; sample size precluded such stratification. Future studies with larger sample sizes should consider stratification by root resorption stage or age to further elucidate the impact of these factors on treat- ment outcomes. Preoperative pain was analyzed, but pain measures are subjective, and the lack of standardization or subgroup analysis based on preoperative symptoms is a potential source of bias. Therefore, future studies should also consider stratified analyses based on preoperative symptoms to clarify their influence. The follow-up period was relatively short. Despite these limitations, our findings support the use of rotary NiTi instruments with ultrasonic irrigation in primary teeth. Future multicenter, large-sample prospective randomized controlled trials with cost-effec- tiveness analysis are needed. Extended follow-up, larger samples, and CBCT imaging would improve evaluation. Further research should clarify the mechanisms and clinical value of advanced techniques.

  Comparison of rotary NiTi files with ultrasonic irrigation and manual K-files with syringe irrigation in primary molar pulpectomy: A retrospective cohort study · 2026 · DOI

• In conclusion, and within the limitations of this preliminary clinical trial, REPs using NeoPutty may represent a promis- ing alternative treatment option for mature necrotic teeth with periapical radiolucency, but further research is needed to vali- date the current findings.

  The outcome of pulp revascularization of necrotic mature permanent teeth with periapical lesions using platelet-rich fibrin versus induced bleeding: a prospective preliminary randomized clinical trial · 2026 · DOI

• The network meta-analysis stratified mature permanent teeth but did not separately analyze outcomes for specific tooth types (molars vs. premolars vs. incisors) or by caries depth/location, which may differentially affect hemostasis control and restoration margins in pulpotomy procedures. Future RCTs should report subgroup analyses of absolute success rates for bioactive materials disaggregated by tooth type and caries extent.

  Decision-ready evidence for vital pulp therapy: a network meta-analysis of bioactive materials in mature permanent teeth · 2026 · DOI

• Diagnostic thresholds for symptomatic teeth in vital pulp therapy studies were heterogeneous, introducing classification noise that could not be fully eliminated even with composite outcome definitions and sensitivity analyses. Standardized diagnostic criteria and symptom severity scales (e.g., Visual Analogue Scale pain scoring, percussion response grading) should be adopted prospectively in RCTs comparing pulpotomy outcomes in symptomatic mature permanent teeth.

  Decision-ready evidence for vital pulp therapy: a network meta-analysis of bioactive materials in mature permanent teeth · 2026 · DOI

• Follow-up attrition and uneven time windows limited certainty of evidence beyond 24 months for several bioactive material comparisons in mature permanent teeth undergoing vital pulp therapy. Prospective cohort studies with standardized follow-up intervals at 3, 5, and 10 years post-pulpotomy or pulp capping are needed to establish durability of modern calcium-silicate cements and assess long-term success decay patterns.

  Decision-ready evidence for vital pulp therapy: a network meta-analysis of bioactive materials in mature permanent teeth · 2026 · DOI

• Unit-of-analysis issues from multiple teeth per patient were rarely addressed at source in included studies, leaving potential residual clustering unaccounted for in the network meta-analysis of pulpotomy and direct pulp capping outcomes. Future trials should employ patient-level or tooth-level statistical models with appropriate variance adjustment to eliminate this confounding.

  Decision-ready evidence for vital pulp therapy: a network meta-analysis of bioactive materials in mature permanent teeth · 2026 · DOI

• Moderator variables critical to vital pulp therapy outcomes—specifically hemostasis regimen/duration, timing of same-visit restoration placement, and isolation breach frequency—were inconsistently reported across included studies, preventing robust meta-regression analysis. Future RCTs in pulpotomy and direct pulp capping should prospectively document and stratify these operative factors to quantify their independent contribution to success rates.

  Decision-ready evidence for vital pulp therapy: a network meta-analysis of bioactive materials in mature permanent teeth · 2026 · DOI

• Evidence networks for laser-assisted vital pulp therapy, PRP/PRF, and potassium nitrate bioactive materials were sparse, reducing precision and inflating rank volatility in network meta-analysis comparisons. Direct head-to-head randomized controlled trials comparing these materials against calcium-silicate cements (MTA, Biodentine) at standardized timepoints are needed to establish reliable rankings.

  Decision-ready evidence for vital pulp therapy: a network meta-analysis of bioactive materials in mature permanent teeth · 2026 · DOI

• Periapical healing is a slow process that may require 12–48 months for complete resolution, and the stability of the observed clinical improvement beyond 6 months remains unknown (27). The antimicrobial efficacy of the tested protocols against the broader endodontic microbiome, particularly obligate anaerobes, remains to be elucidated. Several limitations of this study warrant acknowledgment when interpreting the findings. A key limitation is the 6-month follow-up period, which, while providing useful short-term outcome data, is insufficient for definitive assessment of long-term treatment success.

  Comparative efficacy of semiconductor laser and sodium hypochlorite irrigation for elimination of Enterococcus faecalis in root canals · 2026 · DOI

• The study evaluated only a limited number of sealer types (RealSeal SE, AH Plus, SafeEndo EpoxySeal, SafeEndo BioActive RCS); evaluation of additional modern sealers is needed.

  Effect of antioxidants on dentinal tubular penetration of root canal sealers in sodium hypochlorite treated root canal dentin: a systematic review · 2026 · DOI

• The evidence base is limited by small sample sizes, inconsistent reporting of baseline tooth characteristics, and variability in RET protocols and imaging modalities. Restricting inclusion to RCTs improved internal validity but reduced the number of eligible studies. Meta-analysis was not possible because of substantial heterogeneity, and publication bias could not be meaningfully assessed with fewer than ten studies.

  From blood to biology: evaluating platelet-rich plasma as a scaffold in regenerative endodontics — a systematic review · 2026 · DOI

• BACKGROUND: The single-cone obturation technique with iRoot SP demonstrated strong filling capacity in circular root canals; however, its sealing ability in oval root canals remains underexplored.

  Sealing ability of the single-cone obturation technique with bioceramic sealer iRoot SP in oval root canals: an in vitro study · 2025 · DOI

• SETTINGS AND DESIGN: Various studies have opined on the impact of preparation form on the marginal fit of endocrown, but studies on the effect on the marginal fit of digitally milled endocrown with and without ferrule are sparse.

  Comparative evaluation of marginal fit accuracy of two different designs of endocrown manufactured through CAD-CAM system: An in vitro study · 2025 · DOI

• The lack of extruded AH Plus on the radiograph does not automatically mean that it was completely removed from the periradicular tissues, as the disappearance might be due to resorption of barium sulfate from the AH Plus composition rather than actual sealer resorption.

  HEALING OF APICAL PERIODONTITIS AFTER UNINTENTIONAL EXTRUSION OF AH PLUS SEALER: A RETROSPECTIVE RADIOGRAPHIC ASSESSMENT · 2025 · DOI

• CONCLUSIONS: Despite the limitations of the present study, although a greater percentage of healing was observed in the LAI-SWEEPS and PUI groups, irrigation procedures had no statistically significant effect on the healing of periapical lesions with a single root canal at the 12-month follow-up.

  Association between the irrigation-agitation techniques and Periapical Healing of large periapical lesions: a Randomized Controlled Trial · 2024 · DOI

• Numerous systematic reviews (SRs) have produced conflicting findings on engine-driven nickel-titanium reciprocating instruments (reciprocating instruments) since Yared's seminal study 15 years ago.

  Fifteen years of engine‐driven nickel–titanium reciprocating instruments, what do we know so far? An umbrella review · 2024 · DOI

• Background/purpose: The mineralized tissue-inductive ability and anti-inflammatory properties of hydraulic calcium silicate-based (HCSB) sealers have not been fully elucidated.

  Hydraulic calcium silicate-based root canal sealers mitigate proinflammatory cytokine synthesis and promote osteogenesis in vitro · 2023 · DOI

• However, there are some conflicting reports about their various impacts; hence, the present systematic review study aimed to evaluate the effect of MOP on root resorption, pulp vitality, and the biological changes of teeth subjected to OTM.

  The effect of micro-osteoperforation on root resorption, pulp vitality, and biological changes of teeth subjected to orthodontic tooth movement: A systematic review study · 2023 · DOI

• The objective of this study was to investigate the presence of culturable bacteria, endotoxins (LPS) and lipoteichoic acid (LTA) levels in teeth with normal vital pulp (NVP) with intact crowns (IC) and those with coronal restoration (CR) limited to the enamel level.

  Clinical evaluation of culturable bacteria, endotoxins and lipoteichoic acid in teeth with vital normal pulp tissues · 2023 · DOI

Most-cited papers in Endodontics and Root Canal Treatments

• On the causes of persistent apical periodontitis: a review · International Endodontic Journal · 2006 · 788 citations
• Mechanisms of antimicrobial activity of calcium hydroxide: a critical review · International Endodontic Journal · 1999 · 649 citations
• Passive ultrasonic irrigation of the root canal: a review of the literature · International Endodontic Journal · 2007 · 577 citations
• Outcome of primary root canal treatment: systematic review of the literature – Part 2. Influence of clinical factors · International Endodontic Journal · 2007 · 558 citations
• Mechanical preparation of root canals: shaping goals, techniques and means · Endodontic Topics · 2005 · 556 citations
• Outcome of secondary root canal treatment: a systematic review of the literature · International Endodontic Journal · 2008 · 481 citations
• Outcome of primary root canal treatment: systematic review of the literature – Part 1. Effects of study characteristics on probability of success · International Endodontic Journal · 2007 · 447 citations
• Microorganisms from canals of root-filled teeth with periapical lesions · International Endodontic Journal · 2003 · 441 citations
• Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis · International Endodontic Journal · 1997 · 439 citations
• European Society of Endodontology position statement: Revitalization procedures · International Endodontic Journal · 2016 · 382 citations

Most recent work

• Clinical outcomes of regenerative endodontic procedures compared with apexification in young immature necrotic teeth: a systematic review of randomized controlled trials · Odontology · 2026
• Spatiotemporal Analysis Reveals Mechanisms Controlling Reactive Oxygen Species and Calcium Interplay Following Root Compression · bioRxiv · 2026
• Advantages and limitations of the rubber dam. Part 1: introduction, methods and key findings · Dental Update · 2026
• Evaluation of bone healing using fractal analysis in immature permanent teeth with apical periodontitis treated with three different techniques · Oral Radiology · 2026
• A comparative evaluation of setting time in the presence of blood contamination of four root end filling biomaterials (MTA angelus, biodentine, endosequence root repair material, bio-C repair) An in-vitro study · Endodontology · 2026
• Evaluation of pushout bond strength and marginal adaptation of pullulan-modified mineral trioxide aggregate as root-end filling material – In vitro analysis · Endodontology · 2026
• <scp> <i>Enterococcus faecalis</i> </scp> and Endodontic Treatment Failure: A Qualitative Systematic Review of Its Role and Elimination Strategies · Australian Endodontic Journal · 2026
• Comparison of external apical root resorption and repair levels induced by PowerScope and Forsus fatigue resistant device appliances · Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie · 2026
• Endodontic implications of hypercementosis: A systematic review of anatomical challenges and therapeutic strategies · Japanese Dental Science Review · 2026
• From blood to biology: evaluating platelet-rich plasma as a scaffold in regenerative endodontics — a systematic review · Journal of Baghdad College of Dentistry · 2026

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