The impact of bone grafting with/without barrier membrane placement on the outcome of apical surgery: A systematic review and meta-analysis.

BACKGROUND: Regenerative techniques are increasingly being advocated in endodontic apical surgery (AS) to enhance the healing of periapical lesions. Various grafting and membrane materials are employed as adjuncts to modern AS. OBJECTIVES: This systematic review aimed to answer the following PICO question: In patients with apical periodontitis (P) what is the impact of bone grafting with/without barrier membrane materials (I) compared with surgery without grafting materials (C) on the outcome of AS evaluated clinically and radiographically (O). METHODS: A systematic search was conducted in four databases (Embase, Web of Science, PubMed and Cochrane Central Register of Controlled Trials) until 1 August 2023. Google Scholar was also manually searched. Studies with a prospective randomized design were included. Cochrane risk-of-bias (RoB) tool 2.0 assessed bias. Two independent reviewers performed the study selection, data extraction and appraisal of studies. Meta-analysis was performed using R3.5.1 software. RESULTS: From the identified 2582 studies, eight randomized clinical trials were included for meta-analysis. Two studies had low RoB, while six had some concerns. Analysis revealed significantly better outcomes when surgery involved bone regeneration techniques than conventional surgery (OR = 2.18, 95% CI: 1.32-4.31, p = .004). Subgroup analyses on individual grafts (OR = 0.22, 95% CI: -0.99 to 1.44, p = .720) (OR = -0.09, 95% CI: -1.42 to 1.23, p = .885) and membranes (OR = -1.09, 95% CI: -2.94 to 0.76, p = .247) and their combinations (OR = 0.03, 95% CI: -1.50 to 1.55, p = .970) did not yield any significant results. The type of membrane used did not significantly impact the outcome (OR = -1.09, 95% CI: -2.94 to 0.76, p = .247) nor did altering the combination of graft/membrane. DISCUSSION: This systematic review examined the effects of bone grafting with/without membrane placement on the outcome of AS. It highlights the potential advantages of regenerative techniques and the need for further research in this area. CONCLUSIONS: Based on current evidence, bone grafting with/without barrier membrane placement significantly improves healing after AS. Subgroup analysis of resorbable membranes or grafting did not significantly influence the outcome. The combination of membrane and graft was also not significant. Future well-designed, randomized controlled trials in this area are essential before these materials can be recommended for routine use to enhance healing outcomes in AS. REGISTRATION: PROSPERO (CRD42021255171).

Isolation and Culture of Primary Human Dental Pulp Cells-A Description of Technical and Methodological Steps to Maximise Predictability and Yield.

The dental pulp has critical functions in tooth development as well as an ongoing role in promoting and maintaining the vitality of teeth. In particular, its regenerative ability allows dental tissues to be restored following damage caused by traumatic injury or caries. Regenerative endodontic procedures aim to utilise these processes to stimulate dental pulp repair in a minimally invasive manner and reduce the need for more invasive procedures such as root canal treatment. Dental pulp is a source of dental pulp cells (DPCs), which has a subpopulation of dental pulp stem cells (DPSCs), which are attractive for use in regenerative medicine due to their high proliferation rate, ability to differentiate into multiple cell types, and their preserved vitality following cryopreservation. The development of next-generation clinical therapeutics that maximise the potential of dental pulp relies on strong empirical evidence arising from in vitro experimentation. Here, we describe a modified method for the efficient isolation of primary human DPCs from sound third molar teeth for culture using an explant outgrowth method on basement membrane-coated flasks, as well as using high-resolution macro-photography to illustrate the methods. Critically, steps are taken to minimise potential physical and mechanical trauma to the cells and maximise yield. Human DPCs cultured using this method can be further expanded in cell culture flasks to facilitate their use in various in vitro experimental procedures.

Investigating the technical quality of undergraduate endodontic treatment in a primary care-based dental school.

Introduction The success of root canal treatment (RCTx) relies on the technical quality of the root canal filling, often assessed through radiographic evaluation.Aims This audit aims to evaluate the technical proficiency of Peninsula Dental School (PDS) undergraduate dental students in RCTx, comparing it with established European standards.Design Conducted as a retrospective study, this evaluation focuses on assessing the technical quality of RCTx performed by undergraduate dental students at PDS across various academic years.Setting PDS, a primary care-based dental school in the UK, serves as the focal point for this evaluation.Materials and methods Reviewed 2021-2022 endodontic cases by supervised undergraduates. Analysed radiographs for obturation, voids and errors based on established benchmarks. Randomly selected unbiased cases, assessing voids, filling proximity, missed canals and canal anatomy preservation.Interventions Comparative analysis of RCTx quality between PDS students and counterparts from other dental schools, exemplified by Dublin Dental University Hospital (DDUH).Results Findings revealed that 62.07% of single-rooted and 60% of multi-rooted teeth treated by PDS students met European standards.Discussion The implications highlight the proficiency of PDS students in RCTx, comparing favourably to DDUH.Conclusion Recommendations emphasise conducting regular educational audits in dental schools to continually enhance RCTx techniques and ensure high-quality clinical teaching.

Multiple External Cervical Resorption Lesions in Patient with Graft versus Host Disease Treated with Systemic Bleomycin: A Case Report.

The phenomenon of multiple external cervical root resorption (ECRR) lesions in a single patient is rare but may have a link with the chemotherapeutic agent bleomycin. This case details an adult male with multiple ECRR lesions that developed following chemotherapy. His treatment regimen for Hodgkin's lymphoma included the chemotherapeutic antibiotic bleomycin, which has previously been linked with development of multiple ECRR lesions. The patient developed graft versus host disease following an allogeneic stem cell transplant, which could have a significant role in the development and promotion of the ECRR lesions. In total, 8 teeth developed ECRR, and all the known causative factors were excluded when examined. To our knowledge, this is only the second reported case in the literature to link bleomycin to multiple ECRR lesions. This case report aims to bring the reader's attention to the fact that multiple cervical resorption lesions can develop simultaneously. These lesions can be difficult to diagnose and treat and are often misdiagnosed as caries. Finally, the reader should consider the possible role of bleomycin and graft versus host disease in development of multiple lesions of ECRR.

The Reparative Function of MMP13 in Tertiary Reactionary Dentinogenesis after Tooth Injury.

MMP13 gene expression increases up to 2000-fold in mineralizing dental pulp cells (DPCs), with research previously demonstrating that global MMP13 deletion resulted in critical alterations in the dentine phenotype, affecting dentine-tubule regularity, the odontoblast palisade, and significantly reducing the dentine volume. Global MMP13-KO and wild-type mice of a range of ages had their molar teeth injured to stimulate reactionary tertiary dentinogenesis. The response was measured qualitatively and quantitatively using histology, immunohistochemistry, micro-CT, and qRT-PCR in order to assess changes in the nature and volume of dentine deposited as well as mechanistic links. MMP13 loss affected the reactionary tertiary dentine quality and volume after cuspal injury and reduced Nestin expression in a non-exposure injury model, as well as mechanistic links between MMP13 and the Wnt-responsive gene Axin2. Acute pulpal injury and pulp exposure to oral fluids in mice teeth showed upregulation of the MMP13 in vivo, with an increase in the gene expression of Mmp8, Mmp9, and Mmp13 evident. These results indicate that MMP13 is involved in tertiary reactionary dentine formation after tooth injury in vivo, potentially acting as a key molecule in the dental pulp during dentine-pulp repair processes.

4-Year Pulp Survival in a Randomized Trial on Direct Pulp Capping.

INTRODUCTION: This study aimed to assess pulp survival in a randomized trial on pulp lavage in adult nonpainful posterior teeth with carious pulp exposure. The treatment included complete caries excavation, direct pulp capping with mineral trioxide aggregate, and immediate restoration with composite resin. METHODS: Fluid was collected from the pulp wound to assess matrix metalloproteinase-9 (MMP-9) and total protein values. Before pulp capping, cavities were randomly (block randomization, n = 48) washed with a physiological saline or a sodium hypochlorite solution (2.5% NaOCl). Treatment outcome was assessed clinically (cold test) and radiographically after at least 1 year and again after at least 3 years. Painful failures were differentiated from nonpainful failures. Pulp survival was estimated using the Kaplan-Meier method including 95% confidence intervals (CIs) up to 1500 days. RESULTS: From the 96 patients originally enrolled, 73 individuals could be followed continuously. The clinical observations indicated a beneficial and sustained effect of pulp lavage with 2.5% NaOCl over a control treatment with physiological saline solution on estimated pulp survival 1500 days postintervention, with 7% (95% CI, 1%-40%) in the saline group versus 55% (95% CI, 30%-100%) in the NaOCl group. High MMP-9/total protein values in pulpal fluid collected from the exposed site indicated early and painful treatment failures yet were not associated with failures that occurred more than 250 days after intervention. CONCLUSIONS: The low 4-year success rates reported here challenge the concept of direct pulp capping in the cases that were included. NaOCl lavage did not only increase the survival of affected pulps substantially but also particularly diminished painful failures (33% in the NaOCl group vs 62% in the saline group). The lack of the predictive value of MMP-9 assessments beyond early treatment failures points to inflammatory states of the pulp tissue under deep caries, which are not related to neutrophil infiltration.

Implications of root, pulp chamber, and canal anatomy on pulpotomy and revitalization procedures.

OBJECTIVES: This review aims to discuss the implications of anatomy of the root, pulp chamber, and canals on pulpotomy and revitalization procedures (RPs) as treatment alternatives to root canal treatment procedures. METHODS: This narrative review was undertaken to address two main questions - why remove vital pulp tissue in teeth with complex canal anatomy when it can be preserved? And why replace the necrotic pulp in teeth with mature roots with a synthetic material when we can revitalize? This review also aims to discuss anatomical challenges with pulpotomy and revitalization procedures. RESULTS: Maintaining the vitality of the pulp via partial or full pulpotomy procedures avoids the multiple potential challenges faced by clinicians during root canal treatment. However, carrying out pulpotomy procedures requires a meticulous understanding of the pulp chamber anatomy, which varies from tooth to tooth. Literature shows an increased interest in the application of RPs in teeth with mature roots; however, to date, the relation between the complexity of the root canal system and outcomes of RPs in necrotic multi-rooted teeth with mature roots is unclear and requires further robust comparative research and long-term follow-up. CONCLUSIONS: Whenever indicated, pulpotomy procedures are viable treatment options for vital teeth with mature roots; however, comparative, adequately powered studies with long-term follow-up are needed as a priority in this area. RPs show promising outcomes for necrotic teeth with mature roots that warrant more evidence in different tooth types with long-term follow-ups.  CLINICAL RELEVANCE: Clinicians should be aware of the pulp chamber anatomy, which is subject to morphological changes by age or as a defensive mechanism against microbial irritation, before practicing partial and full pulpotomy procedures. RP is a promising treatment option for teeth with immature roots, but more evidence is needed for its applications in teeth with mature roots. A universal consensus and considerably more robust evidence are needed for the standardization of RPs in teeth with mature roots.

Treatment of pulpal and apical disease: The European Society of Endodontology (ESE) S3-level clinical practice guideline.

BACKGROUND: The ESE previously published quality guidelines for endodontic treatment in 2006; however, there have been significant changes since not only in clinical endodontics but also in consensus and guideline development processes. In the development of the inaugural S3-level clinical practice guidelines (CPG), a comprehensive systematic and methodologically robust guideline consultation process was followed in order to produce evidence-based recommendations for the management of patients presenting with pulpal and apical disease. AIM: To develop an S3-level CPG for the treatment of pulpal and apical disease, focusing on diagnosis and the implementation of the treatment approaches required to manage patients presenting with pulpitis and apical periodontitis (AP) with the ultimate goal of preventing tooth loss. METHODS: This S3-level CPG was developed by the ESE, with the assistance of independent methodological guidance provided by the Association of Scientific Medical Societies in Germany and utilizing the GRADE process. A robust, rigorous and transparent process included the analysis of relevant comparative research in 14 specifically commissioned systematic reviews, prior to evaluation of the quality and strength of evidence, the formulation of specific evidence and expert-based recommendations in a structured consensus process with leading endodontic experts and a broad base of external stakeholders. RESULTS: The S3-level CPG for the treatment of pulpal and apical disease describes in a series of clinical recommendations the effectiveness of diagnosing pulpitis and AP, prior to investigating the effectiveness of endodontic treatments in managing those diseases. Therapeutic strategies include the effectiveness of deep caries management in cases with, and without, spontaneous pain and pulp exposure, vital versus nonvital teeth, the effectiveness of root canal instrumentation, irrigation, dressing, root canal filling materials and adjunct intracanal procedures in the management of AP. Prior to treatment planning, the critical importance of history and case evaluation, aseptic techniques, appropriate training and re-evaluations during and after treatment is stressed. CONCLUSION: The first S3-level CPG in endodontics informs clinical practice, health systems, policymakers, other stakeholders and patients on the available and most effective treatments to manage patients with pulpitis and AP in order to preserve teeth over a patient's lifetime, according to the best comparative evidence currently available.

Methodological assessment and overall confidence in the results of systematic reviews with meta-analyses focusing on traumatic dental injuries: A cross-sectional study.

BACKGROUND/AIMS: High methodological quality is required to interpret results of systematic reviews (SRs) in a reliable and accurate manner. The primary aim of this study was to appraise the methodologic quality of SRs with meta-analysis within the field of traumatic dental injuries using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 tool and assess overall confidence in their results. A secondary aim was to identify potential predictive factors associated with methodological quality. MATERIALS AND METHODS: SRs with meta-analyses published in English in the field of traumatic dental injuries from inception to March 2023 were identified. The methodological quality of the included reviews was assessed using the AMSTAR 2 checklist. Two independent evaluators scored each AMSTAR 2 item as "yes" if it was adequately addressed, "partial yes" if it was partially addressed, and "no" if it was not addressed. The overall confidence in the results of each review was classified as "High," "Moderate," "Low," or "Critically low." Using multiple regression, the relationship between five predictor variables (journal impact factor, year of publication, number of authors, journal adherence to Preferred Reporting Items for Systematic reviews and Meta-analyses [PRISMA] guidelines and a priori protocol registration) and the total AMSTAR 2 scores was analyzed. The p-value was 5%. RESULTS: Forty-one SRs were included. The overall confidence in the results of 13 reviews was categorized as "Critically low," 18 as "Low," 3 as "Moderate" and 7 as "High." Among the five predictor variables analyzed statistically, impact factor of the journal and year of publication significantly influenced the total AMSTAR 2 scores. The number of authors, adherence to PRISMA guidelines, and a priori protocol registration had no significant impact on AMSTAR 2 scores. CONCLUSION: The overall confidence in the results of SRs with meta-analysis within the field of traumatic dental injuries was "Low" or "Critically Low" in the vast majority of studies (31 of 41). SRs with meta-analyses published in journals with higher impact factors and more recent publications had significantly higher methodological quality.

Molecular biomarkers for objective assessment of symptomatic pulpitis: A systematic review and meta-analysis.

BACKGROUND: Inflammatory biomarkers are potentially useful targets for pulpal diagnostic tests that can identify pulp status and predict vital pulp treatment (VPT) outcome, however, their accuracy is unknown. OBJECTIVES: (1) Calculate sensitivity, specificity and diagnostic odds ratio (DOR) of previously investigated pulpitic biomarkers; (2) Determine if biomarker levels discriminate between clinical diagnoses of pulpitis based on the presence or absence of spontaneous pain (3) Evaluate if biomarker level can predict VPT outcome. METHODS: Searches: PubMed/MEDLINE, Ovid SP, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, Embase, Web of Science and Scopus in May 2023. INCLUSION: prospective and retrospective observational studies and randomized trials. Participants were humans with vital permanent teeth and a well-defined pulpal diagnosis. EXCLUSION: deciduous teeth, in vitro and animal studies. Risk of bias was assessed with modified-Downs and Black quality assessment checklist. Meta-analysis was performed using bivariate random effect model in Meta-DiSc 2.0 and RevMan and the quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Fifty-six studies were selected, reporting >70 individual biomolecules investigating pulpal health and disease at the gene and protein level. Most studies were of low and fair quality. Among the biomolecules investigated, IL-8 and IL-6 demonstrated a level of diagnostic accuracy with high sensitivity, specificity and DOR to discriminate between healthy pulps and those exhibiting spontaneous pain suggestive of IRP (low-certainty evidence). However, none was shown to have high DOR and the ability to discriminate between pulpitic states (very low certainty evidence). Limited data suggests high levels of matrix metalloproteinase 9 correlate with poorer outcomes of full pulpotomy. DISCUSSION: The inability of identified molecular inflammatory markers to discriminate between dental pulps with spontaneous and non-spontaneous pain should shift the focus to improved study quality or the pursuit of other molecules potentially associated with healing and repair. CONCLUSIONS: Low-quality evidence suggests IL-8 and IL-6 demonstrated level of diagnostic accuracy to discriminate between healthy pulps and those exhibiting spontaneous pain. There is a need for standardized biomarker diagnostic and prognostic studies focusing on solutions that can accurately determine the degree of pulp inflammation. REGISTRATION: PROSPERO CRD42021259305.

Critical analysis of the reporting quality of case reports focusing on dental traumatology using the Preferred Reporting Items for Case reports in Endodontics 2020 checklist: A baseline evaluation prior to checklist publication.

BACKGROUND/AIMS: The Preferred Reporting Items for Case Reports in Endodontics (PRICE) 2020 guidelines were published to help authors produce high-quality case reports. The aim of this study was to use the PRICE 2020 guidelines to appraise a sample of 50 case reports related to dental traumatology that were published before the guidelines were available in order to assess various parameters influencing the reporting quality. METHODS: Fifty case reports published between 2015 and 2019 and related to dental traumatology were randomly selected from the PubMed database. Reports were assessed by two independent evaluators using the PRICE checklist. Each item received a score of "1" if the manuscript met all pertinent criteria, "0" if it was not reported, and "0.5" if it was reported insufficiently. "Not Applicable" (NA) was assigned to items that were irrelevant to a specific report. The estimated total PRICE score for each case report was computed by adding all the scores, with a maximum score of 47 minus any "NA" scores. Descriptive and Inferential statistics (Student's t-test and ANOVA) were used for analysis. RESULTS: The percentage of case reports that fully met each applicable criteria ranged from 0% to 100%. The percentage of case reports partially satisfying each applicable criterion varied from 0% to 88%. There was a significant difference in scores for case reports published in journals with an impact factor compared with those without (p = .042). No significant difference was observed between the mean scores that compared the period of publication. There was no significant difference between journals that followed the CARE guidelines and those that did not. CONCLUSION: Several items within the PRICE 2020 guidelines were either not reported or only partially reported in case reports related to dental traumatology prior to the checklist publication. It is recommended that authors follow the PRICE 2020 guidelines to improve the overall quality of their case reports.

Epigenetic therapeutics in dental pulp treatment: Hopes, challenges and concerns for the development of next-generation biomaterials.

This opinion-led review paper highlights the need for novel translational research in vital-pulp-treatment (VPT), but also discusses the challenges in translating evidence to clinics. Traditional dentistry is expensive, invasive and relies on an outmoded mechanical understanding of dental disease, rather than employing a biological perspective that harnesses cell activity and the regenerative-capacity. Recent research has focussed on developing minimally-invasive biologically-based 'fillings' that preserve the dental pulp; research that is shifting the paradigm from expensive high-technology dentistry, with high failure rates, to smart restorations targeted at biological processes. Current VPTs promote repair by recruiting odontoblast-like cells in a material-dependent process. Therefore, exciting opportunities exist for development of next-generation biomaterials targeted at regenerative processes in the dentin-pulp complex. This article analyses recent research using pharmacological-inhibitors to therapeutically-target histone-deacetylase (HDAC) enzymes in dental-pulp-cells (DPCs) that stimulate pro-regenerative effects with limited loss of viability. Consequently, HDAC-inhibitors have the potential to enhance biomaterial-driven tissue responses at low concentration by influencing the cellular processes with minimal side-effects, providing an opportunity to develop a topically-placed, inexpensive bio-inductive pulp-capping material. Despite positive results, clinical translation of these innovations requires enterprise to counteract regulatory obstacles, dental-industry priorities and to develop strong academic/industry partnerships. The aim of this opinion-led review paper is to discuss the potential role of therapeutically-targeting epigenetic modifications as part of a topical VPT strategy in the treatment of the damaged dental pulp, while considering the next steps, material considerations, challenges and future for the clinical development of epigenetic therapeutics or other 'smart' restorations in VPT.

Characterisation of miRNA Expression in Dental Pulp Cells during Epigenetically-Driven Reparative Processes.

Within regenerative endodontics, exciting opportunities exist for the development of next-generation targeted biomaterials that harness epigenetic machinery, including microRNAs (miRNAs), histone acetylation, and DNA methylation, which are used to control pulpitis and to stimulate repair. Although histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) induce mineralisation in dental pulp cell (DPC) populations, their interaction with miRNAs during DPC mineralisation is not known. Here, small RNA sequencing and bioinformatic analysis were used to establish a miRNA expression profile for mineralising DPCs in culture. Additionally, the effects of a HDACi, suberoylanilide hydroxamic acid (SAHA), and a DNMTi, 5-aza-2'-deoxycytidine (5-AZA-CdR), on miRNA expression, as well as DPC mineralisation and proliferation, were analysed. Both inhibitors increased mineralisation. However, they reduced cell growth. Epigenetically-enhanced mineralisation was accompanied by widespread changes in miRNA expression. Bioinformatic analysis identified many differentially expressed mature miRNAs that were suggested to have roles in mineralisation and stem cell differentiation, including regulation of the Wnt and MAPK pathways. Selected candidate miRNAs were demonstrated by qRT-PCR to be differentially regulated at various time points in mineralising DPC cultures treated with SAHA or 5-AZA-CdR. These data validated the RNA sequencing analysis and highlighted an increased and dynamic interaction between miRNA and epigenetic modifiers during the DPC reparative processes.

DENTAL PATIENT-REPORTED OUTCOMES IN ENDODONTICS - A NARRATIVE REVIEW.

Recently in oral health care settings, the focus of assessing treatment outcomes has shifted from the perspective of the clinician towards that of the patient. Endodontology is a specialty of dentistry concerned with the prevention and treatment of pulp and periapical diseases. Research in endodontology and its associated treatment outcomes have focused mainly on clinician-reported outcomes (CROs) and not dental patient-reported outcomes (dPROs). As a result, there is a need to emphasize the importance and relevance of dPROs to researchers and clinicians. The aim of this review is to present an overview of dPROs and dPROMs within endodontics in an attempt to create a better understanding of the patient experience, highlight the need to place the patient at the center of treatment, enhance patient care and encourage more research into dPROs. The key dPROs following endodontic treatment include pain, tenderness, tooth function, need for further intervention, adverse effects (exacerbation of symptoms, tooth discoloration) and Oral Health-Related Quality of Life. dPROs are important following endodontic treatment because they assist clinicians and patients when they discuss and select the most appropriate management options, help clinicians make decisions on pre-operative assessment, prevention and treatment, and improve the methodology and design of future clinical studies. Clinicians and researchers in endodontology should prioritize patient welfare and undertake routine analyses of dPROs using appropriate and robust measures. Due to the lack of agreement over the reporting and definition of endodontic treatment outcomes, a comprehensive project to define a ``Core Outcome Set for Endodontic Treatment Methods (COSET)'' is currently ongoing. In the future, a new and exclusive assessment tool should be developed to reflect the viewpoints of patients receiving endodontic treatment more accurately.