Discriminatory performance of the pulpal inflammatory biomarkers; Interleukin-8 and TNF-α in patients with symptoms indicative of reversible and irreversible pulpitis: A diagnostic accuracy study.

AIM: The success of vital pulp treatment (VPT) procedures is dependent on an accurate diagnosis of the pulpal inflammatory condition. Compared with current subjective pulpal diagnostic tests, inflammatory molecular biomarkers involved in the pathogenesis of pulpitis represent potential objective indicators of the degree of pulpal inflammation. Therefore, the aim of this study was to quantify level of inflammatory biomarkers - Interleukin 8 (IL-8) and TNF-α in patients diagnosed with reversible pulpitis (RP), irreversible pulpitis (IR) and normal pulp (NP) and investigate their diagnostic accuracy in differentiating between healthy and inflamed conditions. METHODOLOGY: This prospective, cross-sectional study enrolled 72 patients aged 14-53 years with extremely deep carious lesions after establishing a clinical diagnosis of RP (n = 42), symptomatic IR (n = 22) and NP (n = 8). 50 µL of pulpal blood sample was collected from all the patients using a micropipette after pulpal exposure. The level of IL-8 and TNF-α was assessed in pg/mL using enzyme-linked immunosorbent assays. Mann-Whitney U test was applied to establish the association between IL-8/TNF-α level and degree of pulp inflammation. Receiver operating curve (ROC) analysis was carried out to calculate area under the curve (AUC) for RP versus IR. Cut-off values were established using Youden's index. RESULTS: IL-8 and TNF-α levels differed significantly between RP and IR groups (p ≤ .001). The median value of IL-8 in RP and IP groups was 259.8 pg/mL [187.5-310.0] and 1357.8 pg/mL [1036.7-2177.6] respectively. The AUC-ROC curve for RP versus IR was 0.997 with 95.5% sensitivity and 99.76% specificity. The median value of TNF-α in RP and IR groups was 75.4 pg/mL [62.7-95.8] and 157.6 pg/mL [94.1-347.3]. The AUC-ROC curve for TNF-α was 0.812 with a sensitivity and specificity of 59.1% and 92.1%, respectively. IL-8 and TNF-α levels were below detection levels for all NP samples. CONCLUSION: This study showed that pulpal blood could provide an excellent medium for establishing pulpal diagnosis under extremely deep carious lesions. The selected cytokines, IL-8 and TNF-α, demonstrated excellent discriminatory performance for reversible and irreversible pulpitis. Future studies should correlate the IL-8/TNF-α levels with VPT treatment outcomes.

The efficacy of premixed bioceramic sealers versus standard sealers on root canal treatment outcome, extrusion rate and post-obturation pain: A systematic review and meta-analysis.

BACKGROUND: Limited evidence is available regarding the superior clinical properties of bioceramic sealers comparted with traditional standard sealers. OBJECTIVES: This review aimed to answer the following research questions: 'In healthy patients requiring a root canal treatment (P), what is the efficacy of premixed bioceramic sealers (I) compared with traditional root canal epoxy resin-based sealers (C) in terms of survival, success rates (PICO1) sealer extrusion and resorption (PICO2) post-obturation pain (PICO3) (O)?' METHODS: Authors independently searched three electronic databases: PubMed (including MEDLINE), Web of Science, Embase and Scopus up to 31 October 2023. This was accompanied by both grey literature and manual search. Detailed selection criteria were applied, namely mature permanent teeth requiring root canal treatment, premixed bioceramic sealer with gutta-percha as an intervention group, a standard filling technique as control group and full-text available in English. A random-effect meta-analysis was used to synthesize the body of evidence regarding the use of bioceramic sealers in root canal treatment and their impact on post-obturation pain. Effect sizes were represented as relative risks on a logarithmic scale for binary outcomes and as mean differences for continuous outcomes. RESULTS: A total of 941 articles were identified. Fifteen Comparative clinical studies were finally included. Eleven were randomized clinical trials, and four were prospective clinical trials with control group. The follow-up of these studies was not greater than 2 years. No publication bias was observed in any study. No significant differences were observed between the two groups in terms of survival and success rates. A small non-significant lower risk of extrusion was observed for bioceramics. A small, non-significantly lower post-operative-pain within 24-h was observed when bioceramics were used. DISCUSSION: The majority of current evidence shows inconsistencies in reporting and is of short-term duration. Robust prospective long-term trials are needed in this area to better support future recommendations. CONCLUSION: This systematic review is the first to analyse several clinical outcomes using premixed sealers. Included studies differed in terms of clinical protocol and operator expertise, but reported a similar outcome when comparing bioceramic versus standard sealers. Tooth survival, treatment outcome, post-operative pain and periapical extrusion were similar and presented no significant differences between the two sealer types. REGISTRATION: PROSPERO database (CRD42023449151).

An international consensus study to identify "what" outcomes should be included in a core outcome set for endodontic treatments (COSET) for utilization in clinical practice and research.

BACKGROUND: Development of a standardized set of topic-specific outcomes known as a Core Outcome Set (COS) is important to address issues of heterogeneity in reporting research findings in order to streamline evidence synthesis and clinical decision making. AIM: The aim of the current international consensus study is to identify "what" outcomes to include in the Core Outcome Set for Endodontic Treatments (COSET). Outcomes of various endodontic treatments (non-surgical root canal treatment, surgical endodontics, vital pulp treatment and revitalization procedures) performed on permanent teeth were considered. METHODS: A standard validated methodology for COS development and reporting was adopted. The process involved identification of existing outcomes through four published scoping reviews. This enabled creation of a list of outcomes to be prioritized via semi-structured patient interviews, e-Delphi process and a consensus meeting with a range of relevant global stakeholders. Outcomes were prioritized using a 1-9 Likert scale, with outcomes rated 7-9 considered critical, 4-6 are important and 1-3 are less important. Outcomes rated 7-9 by ≥70% and 1-3 by <15% of participants were considered to achieve consensus for inclusion in the COS. The outcomes that did not achieve consensus in the first round were considered for further prioritization in the second Delphi round and consensus meeting. Final decisions about the outcomes to include in COSET were made by voting during the consensus panel meeting using the Zoom Poll function. RESULTS: A total of 95 participants including patients contributed to the COS development process. The consensus panel recommended, with strong consensus, eight outcomes shared across all treatment modalities for inclusion in COSET: pain; signs of infection (swelling, sinus tract); further intervention/exacerbation; tenderness to percussion/palpation; radiographic evidence of disease progression/healing; function; tooth survival; and patient satisfaction. Additional treatment specific outcomes were also recommended. DISCUSSION: Many of the outcomes included in COSET are patient reported. All should be included in future outcomes studies. CONCLUSION: COSET identified outcomes that are important for patients and clinicians and validated these using a rigorous methodology. Further work is ongoing to determine "how" and "when" these outcomes should be measured.

Microstructural Evaluation of the Mineralized Apical Barrier Induced by a Calcium Hydroxide Paste Containing Iodoform: A Case Report.

INTRODUCTION: A 65-year-old man had nonsurgical retreatment using an iodoform and calcium hydroxide paste in a maxillary left canine with persistent apical periodontitis. An apical mineralized barrier (AMB) was observed 3-months postoperatively. Unfortunately, the tooth was extracted due to a cementum tear. This provided an opportunity to analyze the AMB histologically, as there is a lack of previous reports on its microstructure. METHODS: After extraction and removal of the granulation tissue from the root surface, the canine was processed, and observed using micro-computed tomography (µCT) and light microscopy. Thereafter, the specimen was resin-embedded specimen was evaluated by scanning electron microscopy, micro-X-ray fluorescence spectroscopy and Raman spectroscopy to understand the mechanism and nature of the AMB formation during apical healing. RESULTS: Nonsurgical retreatment was clinically successful based on the absence of clinical symptoms of apical periodontitis and the radiographic presence of an AMB. The AMB was opaque and could be readily differentiated from dentin under a light microscope. Micro-computed tomography analysis revealed that the AMB had the same mineral density as dentin. Scanning electron microscopy revealed that the AMB had two distinct layers based on the size of the calcified particles. Elemental mapping using micro-X-ray fluorescence spectroscopy showed that the localization of calcium and phosphorus differed between AMB and other areas of biomineralization. Raman spectral mapping revealed that the surface layer of the AMB consisted of collagen, calcium carbonate, and hydroxyapatite. CONCLUSIONS: This study explored new analytical methods for elucidating the apical wound-healing process and the nature of the mineralized repair. The findings provided detailed information on the AMB highlighting a bilaminar structure with high calcium components higher on the inside and a brightness similar to cementum not dentin and the presence of hydroxyapatite.

Repair of an Extensive External Cervical Resorption Lesion Using Intentional Replantation with Crown Rotation.

Treatment of large external cervical resorption (ECR) lesions may be compromised, rendering the tooth unrestorable. Intentional replantation is a potential treatment option depending on the site and extent of ECR. We present a case of a large ECR successfully managed with intentional replantation with rotation of the tooth. The female patient consulted the hospital clinic, with an extensive palatal ECR on the maxillary lateral incisor. Routine planar radiographs and cone-beam computed tomography demonstrated a larger palatal than the ECR lesion (Heithersay Class III and Patel's Class 2Bp) not amenable to nonsurgical treatment. Intentional replantation after short-term extrusion was planned. The defect was restored, then a palatal ferrule was achieved by rotating the tooth by 180°. At the 18-month follow-up, the periradicular and periodontal tissues remained healthy, and no other symptoms were reported. In conclusion, this successful video-illustrated clinical case highlights the benefits of intentional replantation in saving teeth with advanced ECR.

Critical analysis of the reporting quality of animal studies within Endodontics using the Preferred Reporting Items for Animal Studies in Endodontics (PRIASE) 2021 quality standard checklist.

AIM: To critically evaluate the reporting quality of a random sample of animal studies within the field of endodontics against the Preferred Reporting Items for Animal Studies in Endodontics (PRIASE) 2021 checklist and to investigate the association between the quality of reporting and several characteristics of the selected studies. METHODOLOGY: Fifty animal studies related to endodontics were randomly selected from the PubMed database with publication dates from January 2017 to December 2021. For each study, a score of '1' was given when the item of the PRIASE 2021 checklist was fully reported, whereas a score of '0' was given when an item was not reported; when the item was inadequately or partially reported, a score of '0.5' was given. Based on the overall scores allocated to each manuscript, they were allocated into three categories of reporting quality: low, moderate and high. Associations between study characteristics and reporting quality scores were also analysed. Descriptive statistics and Fisher's exact tests were used to describe the data and determine associations. The probability value of .05 was selected as the level of statistical significance. RESULTS: Based on the overall scores, four (8%) and 46 (92%) of the animal studies evaluated were categorized as 'High' and 'Moderate' reporting quality, respectively. A number of items were adequately reported in all studies related to background (Item 4a), relevance of methods/results (7a) and interpretation of images (11e), whereas only one item related to changes in protocol (6d) was not reported in any. No associations were confirmed between reporting quality scores and number of authors, origin of the corresponding author, journal of publication (endodontic specialty vs. non- specialty), impact factor or year of publication. CONCLUSIONS: Animal studies published in the specialty of endodontics were mostly of 'moderate' quality in terms of the quality of reporting. Adherence to the PRIASE 2021 guidelines will enhance the reporting of animal studies in the expectation that all future publications will be high quality.

Development and preliminary validation of an Objective Structured Assessment of Technical Skills (OSATS) for a partial pulpotomy procedure.

AIM: To develop an Objective Structured Assessment of Technical Skills (OSATS) tool for partial pulpotomy and to preliminary assess the validity of this tool. Secondary objectives were to check internal consistency as well as the interrater reliability of this specific checklist and to compare it with the previously validated global rating score (GRS). METHODOLOGY: The study assessed three groups of dental participants (mix of practitioners or students) possessing differing levels of clinical experience (7 novices, 7 intermediates, 7 experts), during a partial pulpotomy procedure on a simulated tooth with deep caries, using a bespoke procedure-specific checklist (PSC) and the GRS. Two independent examiners received the study participants in groups of two, in order to be able to directly observe their actions and grade the different steps of the procedure from 1 to 5 on the PSC and GRS. The internal validity of the specific checklist was assessed using a Cronbach's alpha test. As the construct validity of such a tool can be determined when the tool differentiates performance based on the level of experience, the total score of the PSC of the three groups (e.g., novice group, intermediate group, experienced group) were compared using the Kruskal-Wallis and post-hoc Mann-Whitney pairwise U test. The total scores of the GRS were also analysed in the same manner. A correlation test (Correlation Matrices Test) was carried out for the entire sample between the specific checklist and the GRS (on total score). The intraclass correlation coefficient was used to measure the degree of agreement between the two evaluators. The statistical analysis was performed with XLSTAT® and Statistica® (significance p = .05). RESULTS: The partial pulpotomy specific checklist graded from one to five demonstrated good internal consistency (0.86) and a good interrater reliability (0.91), a correct construct validity (p generally < .05) and a good positive correlation with the validated GRS (r = .92). CONCLUSIONS: To address the need to develop education in vital pulp treatment, and more specifically the technical skills assessment of partial pulpotomy, an OSATS-specific checklist was developed and preliminary validated. The checklist will need to be validated in larger cohorts.

Outcome of partial and full pulpotomy in cariously exposed mature molars with symptoms indicative of irreversible pulpitis: A randomized controlled trial.

AIM: The aim of this study was to assess and compare the clinical and radiographic outcome of partial pulpotomy and full pulpotomy using Biodentine in cariously exposed mature molar teeth with symptoms indicative of irreversible pulpitis. METHODOLOGY: This study is an unicentric, double-arm, randomized superiority clinical trial with parallel experimental groups, registered under CTRI (CTRI/2019/12/022559). Fifty mature permanent molar teeth with carious exposures with symptoms indicative of irreversible pulpitis were randomly allocated equally into two groups. Partial pulpotomy (PP) and full pulpotomy (FP) were performed in the first and second group, respectively, following standardized protocols. Exposed pulp tissue was removed up to a depth of 2-3 mm for partial pulpotomy, whereas complete coronal pulp tissue was removed up to the level of root orifices for full pulpotomy. Haemostasis was achieved with placement of 2.5% sodium hypochlorite-moistened cotton pellets placed on amputated pulp tissue for a maximum of 10 min. Biodentine was used as the pulp capping material. Pain scores were evaluated using 11-point Visual Analogue Scale (VAS) preoperatively, at 24 h, 48 h and 7th day after the intervention(s). Clinical and radiographic evaluation was done at 3 months, 6 months and 1 year. The data were statistically analysed using chi-squared test, Mann-Whitney U-test, Friedman's test and Wilcoxon signed-rank test. The significance level was pre-determined at p < .05. Cumulative survival probabilities were assessed at 12 months using Kaplan-Meier analysis. RESULTS: Intra-group analysis of pain scores revealed significant reduction in pain scores preoperatively and at 24 h, 48 h and 7th day in both the groups. However, the difference in the pain score(s) reduction between both the groups was not statistically significant at any time interval (p > .05). At 1-year follow-up, the success rate was 88% (22/25) and 91.6% (22/24) for PP and FP respectively (p > .05). CONCLUSIONS: Partial pulpotomy showed comparable results to full pulpotomy in terms of clinical/radiographic treatment outcome. If the long-term results remain the same, partial pulpotomy can be proposed as an alternative treatment modality for mature teeth with cariously exposed pulp tissue presenting with signs of symptomatic irreversible pulpitis.

Outcomes reporting in systematic reviews on non-surgical root canal treatment: A scoping review for the development of a core outcome set.

BACKGROUND: Studies related to non-surgical root canal treatment are amongst the most frequently performed clinical studies in endodontics. However, heterogeneity in reporting outcomes and lack of standardization is a significant challenge to evidence synthesis and guideline development. OBJECTIVES: The aims of the present scoping review were to (a) identify outcomes reported in systematic reviews evaluating non-surgical root canal treatment; (b) identify how and when the reported outcomes were measured; (c) assess possible selective reporting bias in the included studies. The information obtained in this study should inform the development of a core outcome set (COS) for non-surgical root canal treatment. METHODOLOGY: Structured literature searches were performed to identify systematic reviews on non-surgical root canal treatments published in English between January 1990 and December 2020. Two reviewers undertook study selection and data extraction. Outcomes were categorized according to a healthcare taxonomy into five core areas (survival, clinical/physiological changes, life impact, resource use, and adverse events). The outcome measurement tools and length of follow-up were recorded. RESULTS: Seventy-five systematic reviews were included, of which 40 included meta-analyses. Most reviews reported on physiological and clinical outcomes, primarily pain and/or radiographic assessment of periapical status, and a variety of measurement tools and scales were used. Few reviews focused on tooth survival, life impact, resources, and adverse events. The heterogeneity amongst the reviews was large on all parameters. Less than 40% of the reviews assessed the risk of selective reporting. DISCUSSION: Overall aims of the included reviews were highly heterogenic; thus, outcomes and how they were measured also varied considerably. Patient-centred outcomes and the use of resources were rarely reported on. CONCLUSIONS: Most studies reported on physiological and clinical outcomes, in particular pain and/or radiographic healing. Measurement tools, scales, thresholds, and follow-up periods varied greatly within each outcome, making comparison across studies complicated. Less than 40% of the reviews assessed risk of selective reporting; thus, selective bias could not be ruled out. The presented information on reported outcomes, measurement tools and scales, and length of follow-up may guide the planning of future research and inform the development of a COS for non-surgical root canal treatment.

Preclinical 3D-printed laboratory simulation of deep caries and the exposed pulp reduced student anxiety and stress, while increasing confidence and knowledge in vital pulp treatment.

AIM: To evaluate the impact of a preclinical laboratory session using 3D printed teeth on dental student stress, anxiety, confidence and knowledge when treating deep caries and pulp exposure. METHODOLOGY: This was a two-centre controlled study, with randomized distribution of students into two groups: a vital pulp treatment (VPT) lecture-only (control) group and a VPT-lecture combined with a VPT-laboratory (experimental) group. In both universities, preclinical students with endodontic or operative dentistry laboratory sessions could participate. All students were invited to the lecture. Two weeks later (timepoint-T1), both groups completed validated and bespoke questionnaires and scales to evaluate their stress (Stress-VAS), anxiety (STAI Trait [T] and State [S]), self-confidence and knowledge. Thereafter, only the experimental group attended the hands-on laboratory session demonstrating the techniques of selective caries removal and partial pulpotomy on a commercial 3D-printed tooth. Two weeks later (timepoint-T2), the participants from both groups repopulated the same questionnaires and VAS. The control group had the laboratory session after the completion of the study. The statistical analysis was performed with Statistica® (significance p = .05). The homogeneity between the two samples was checked by Khi2 and Student tests. Stress-VAS, STAI-S, confidence and knowledge scores were compared within each group, and between the two groups, at T1 and T2, with a repeated measures anova test (+/-Tukey post-hoc test). RESULTS: The groups comprised 54 students each, with no statistical difference between the groups regarding demographic, academic data and STAI-T score. The two groups had no significant difference of Stress-VAS, STAI-S, confidence and knowledge scores at T1 while they presented a significant difference in stress, anxiety and confidence scores at T2, but with no significant difference in knowledge score. However, knowledge score, as other parameters, improved significantly between T1 and T2 in the experimental group. CONCLUSIONS: The addition of a laboratory session using 3D-printed teeth that simulated deep caries and pulp exposure management, significantly reduced the stress and anxiety of students and increased their confidence. Within the limitations of this study, the benefit of introducing new technology in increasing student confidence and reducing stress offers opportunity for educational improvement in the VPT and cariology areas.

A bibliometric analysis of the dental scientific literature on COVID-19.

OBJECTIVES: The rapid production of a large volume of literature during the early phase of the COVID-19 outbreak created a substantial burden for clinicians and scientists. Therefore, this manuscript aims to identify and describe the scientific literature addressing COVID-19 from a dental research perspective, in terms of the manuscript origin, research domain, study type, and level of evidence (LoE). MATERIALS AND METHODS: Data were retrieved from Web of Science, Scopus, and PubMed. A descriptive analysis of bibliographic data, collaboration network, and keyword co-occurrence analysis were performed. Articles were further classified according to the field of interest, main research question, type of study, and LoE. RESULTS: The present study identified 296 dental scientific COVID-19 original papers, published in 89 journals, and co-authored by 1331 individuals affiliated with 429 institutions from 53 countries. Although 81.4% were single-country papers, extensive collaboration among the institutions of single countries (Italian, British, and Brazilian institutions) was observed. The main research areas were as follows: the potential use of saliva and other oral fluids as promising samples for COVID-19 testing, dental education, and guidelines for the prevention of COVID-19 transmission in dental practice. The majority of articles were narrative reviews, cross-sectional studies, and short communications. The overall LoE in the analyzed dental literature was low, with only two systematic reviews with the highest LoE I. CONCLUSION: The dental literature on the COVID-19 pandemic does not provide data relevant to the evidence-based decision-making process. Future studies with a high LoE are essential to gain precise knowledge on COVID-19 infection within the various fields of Dentistry. CLINICAL RELEVANCE: The published dental literature on COVID-19 consists principally of articles with a low level of scientific evidence which do not provide sufficient reliable high-quality evidence that is essential for decision making in clinical dental practice.

Environmental sustainability in endodontics. A life cycle assessment (LCA) of a root canal treatment procedure.

BACKGROUND: To analyse via life cycle analysis (LCA) the global resource use and environmental output of the endodontic procedure. METHODOLOGY: An LCA was conducted to measure the life cycle of a standard/routine two-visit RCT. The LCA was conducted according to the International Organization of Standardization guidelines; ISO 14040:2006. All clinical elements of an endodontic treatment (RCT) were input into OpenLCA software using process and flows from the ecoinvent database. Travel to and from the dental clinic was not included. Environmental outputs included abiotic depletion, acidification, freshwater ecotoxicity/eutrophication, human toxicity, cancer/non cancer effects, ionizing radiation, global warming, marine eutrophication, ozone depletion, photochemical ozone formation and terrestrial eutrophication. RESULTS: An RCT procedure contributes 4.9 kg of carbon dioxide equivalent (CO2 eq) emissions. This is the equivalent of a 30 km drive in a small car. The main 5 contributors were dental clothing followed by surface disinfection (isopropanol), disposable bib (paper and plastic), single-use stainless steel instruments and electricity use. Although this LCA has illustrated the effect endodontic treatment has on the environment, there are a number of limitations that may influence the validity of the results. CONCLUSIONS: The endodontic team need to consider how they can reduce the environmental burden of endodontic care. One immediate area of focus might be to consider alternatives to isopropyl alcohol, and look at paper, single use instrument and electricity use. Longer term, research into environmentally-friendly medicaments should continue to investigate the replacement of current cytotoxic gold standards with possible natural alternatives. Minimally invasive regenerative endodontics techniques designed to stimulate repair or regeneration of damaged pulp tissue may also be one way of improving the environmental impact of an RCT.

Diabetes Mellitus May Negatively Influence the Outcome of Conventional Nonsurgical Root Canal Treatment.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Association between diabetes and the outcome of root canal treatment in adults: an umbrella review. Nagendrababu V, Segura-Egea JJ, Fouad AF, Pulikkotil SJ, Dummer PMH. Int Endod J 2020;53(4):455-66. SOURCE OF FUNDING: Authors declared that no funding was received to support the study. TYPE OF STUDY/DESIGN: Umbrella review (ie, overarching systematic review of systematic reviews).

Histone Acetylation as a Regenerative Target in the Dentine-Pulp Complex.

If dental caries (or tooth decay) progresses without intervention, the infection will advance through the dentine leading to severe pulpal inflammation (irreversible pulpitis) and pulp death. The current management of irreversible pulpits is generally root-canal-treatment (RCT), a destructive, expensive, and often unnecessary procedure, as removal of the injurious stimulus alone creates an environment in which pulp regeneration may be possible. Current dental-restorative-materials stimulate repair non-specifically and have practical limitations; as a result, opportunities exist for the development of novel therapeutic strategies to regenerate the damaged dentine-pulp complex. Recently, epigenetic modification of DNA-associated histone 'tails' has been demonstrated to regulate the self-renewal and differentiation potential of dental-stem-cell (DSC) populations central to regenerative endodontic treatments. As a result, the activities of histone deacetylases (HDAC) are being recognised as important regulators of mineralisation in both tooth development and dental-pulp-repair processes, with HDAC-inhibition (HDACi) promoting pulp cell mineralisation in vitro and in vivo. Low concentration HDACi-application can promote de-differentiation of DSC populations and conversely, increase differentiation and accelerate mineralisation in DSC populations. Therapeutically, various HDACi solutions can release bioactive dentine-matrix-components (DMCs) from the tooth's extracellular matrix; solubilised DMCs are rich in growth factors and can stimulate regenerative processes such as angiogenesis, neurogenesis, and mineralisation. The aim of this mini-review is to discuss the role of histone-acetylation in the regulation of DSC populations, while highlighting the importance of HDAC in tooth development and dental pulp regenerative-mineralisation processes, before considering the potential therapeutic application of HDACi in targeted biomaterials to the damaged pulp to stimulate regeneration.