Background: Current treatment of immature necrotic permanent teeth with a periapical lesion is regenerative endodontics, which is based on tissue engineering under the triade of stem cells, scaffolds and bioactive molecules.Objectives: This Umbrella Review was aimed to evaluate the success of scaffold and regenerative materials used for the treatment of these teeth, in terms of apical closure, tooth length increase, widening of root canal walls, tissue vitality and periapical lesion repair.Methods: An extensive literature research was carried out in the Medline, ISI Web of Science, and Scopus databases for relevant systematic reviews matching the keyword search strategy. Based on inclusion and exclusion criteria, reviewers independently rated the quality of each study to determine their level of evidence. Methodological quality assessment of each article was obtained using A Measurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool, and risk of bias was assessed with the Risk of Bias in Systematic Reviews (ROBIS) tool.Results: After removing duplicates, 155 articles were found; from which 133 were excluded for being non-relevant and 15 other due to exclusion criteria. One more was discarded after methodological quality evaluation, for a total of six articles remaining. The most common scaffold used was the blood clot, others used were poly lactic-co-glycolic acid and platelet-rich fibrin matrix. The most common regeneration material used was Mineral Trioxide Aggregate (MTA), followed by Biodentine.An increase in tooth length and widening of root canal walls were reported in all selected studies with different proportions, as well as periapical lesion repair. ROBIS analysis showed that only one article had low bias, two were classified as unclear bias, while the remaining three had high risk of bias.Discussion: An exhaustive literature search was carried out applying language filters, high-quality indexed journals, year of publication, which ensures the best quality articles were included. Blood clot was the most used scaffold as is the most easy to place inside the canal and does not require to extract blood from the patient. The use of MTA General characteristics of the articles selectedThe selected systematic reviews and meta-analysis were found in different indexed journals, ranked as Q1-Q4 by Scimago Journal Rank (SJR), published between 2016 and 2020 in the Journal of Endodontics (2), Acta Odontologica Scandinavica (1), Pediatric Dentistry (1), Platelets (1) and Scientific Reports (1). The number of articles included in these systematic reviews ranged between 6 and 26; and the search motors used were PubMed, Scopus, Google Scholar, Medline, ISI Web of Science, Cochrane Library, BVS, Lilacs, BBO, Embase, Central and grey literature. Other general characteristics are listed on Table 5. Materials and methods main findingsScaffolds used were the blood clot, collagen, PLGA, PRFM, whilst the sealing materials used were MTA, Biodentine, Gutta-percha and Portland Cement. The most common scaffold/sealing material...

Background The aim of this study was to measure the dental pulp inflammatory response through neuropeptides (SP and CGRP) as a response to occlusal trauma, orthodontic movements and a combination of both, as well as the angiogenic defense mechanism through VEGF expression, which could be the initial step to mineralized tissue formation. Methods Forty human dental pulp samples were collected from healthy first premolars with extraction indicated due to orthodontic reasons from a sample of 20 patients. Patients were divided into four groups with 10 premolars each (1 mandibular and 1 maxillary premolar from each patient): healthy pulp control group, occlusal trauma group, moderate orthodontic forces group; and occlusal trauma plus moderate orthodontic forces group. Stimuli were applied for 24 h before tooth extraction in all experimental groups. All samples were processed, and SP, CGRP, and VEGF were measured by radioimmunoassay. The Kruskal–Wallis test was performed to assess significant differences among groups and Mann–Whitney’s U post hoc pairwise comparisons were also performed. Results The highest increase in SP, CGRP, and VEGF expressions was found in the occlusal trauma plus orthodontic forces group, followed by the moderate orthodontic forces, the occlusal trauma and the control groups, with statistically significant differences between all groups for each of the 3 peptides analyzed (Kruskal–Wallis p < 0.001). All possible pairwise post-hoc comparisons were also significant for each peptide analyzed (Mann–Whitney’s U p < 0.001). Conclusion SP, CGRP, and VEGF expressions significantly increase in human dental pulps when stimulated by occlusal trauma combined with moderate orthodontic forces, as compared with these two stimuli applied independently. Name of the registry: Importance of Neurogenic Inflammation in the Angiogenic Response of the Dental Pulp as a Defensive Response. Trial registration number: NCT03804034. Date of registration: 01/15/2019 Retrospectively registered. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03804034?term=NCT03804034&draw=2&rank=1.

Background Proper oxygen balance in the dental pulp is essential for cell metabolism. Angiogenesis in the pulp is a constant process during the life of the tooth. Hypoxia indicators in a tissue, such as HIF-1α, as well as vascular destabilization markers, such as ANG2 and its receptor TIE2, are necessary for angiogenesis. Therefore the purpose of this study is to evaluate the expression of HIF-1α, ANG1, ANG2 and TIE2 in dental pulp as early angiogenesis indicators in teeth with complete and incomplete root development. Methods Forty human dental pulps were obtained from freshly extracted third molars divided into two groups: incomplete (n = 20) and complete (n = 20) root development. Dental pulps were stored at − 80 °C, defrosted in an ice bath and re-frozen with their respective thaws to disintegrate the tissue. Three sonication cycles were performed until the tissues were homogenized, then thaw were centrifuged and the supernatant was collected for the detection of the markers to be studied. The samples were processed for the ELISA test using the ELISA-sandwich principle. Student t and Mann–Whitney U tests were performed to determine statistically significant differences between groups. Results In the complete root development, HIF-1α, ANG1, ANG2 and TIE2 expressions were significantly higher than their expression in the incomplete root development group. Conclusions The angiogenic process seems to be a physiological process in the dental pulp. Angiogenic activity is higher in teeth with mature than immature apex teeth.

Background To quantify the expression of SP, CGRP, and VEGF in human dental pulps as a response to occlusal trauma, moderate orthodontic forces, and occlusal trauma plus moderate orthodontic forces simultaneously.Methods Forty human dental pulp samples were collected from healthy premolars indicated for extraction for orthodontic reasons in 20 patients. Patients were divided into four groups with 10 samples each (5 lower and 5 upper premolars from each patient): Healthy pulp control group, occlusal trauma group, moderate orthodontic forces group; and occlusal trauma plus moderate orthodontic forces group. Stimuli were applied for 24 h before tooth extraction in all experimental groups. All samples were processed, and SP, CGRP, and VEGF were measured by radioimmunoassay. The ANOVA test was performed to establish significant differences between groups and Tukey’s HSD post hoc comparisons were also performed.Results The highest increase in SP, CGRP, and VEGF expressions was found in the occlusal trauma plus orthodontic forces group, followed by the moderate orthodontic forces, the occlusal trauma and the control groups, with statistically significant differences between all groups (ANOVA p<0.001). All pairwise post-hoc comparisons were also significant (Tukey HSD p<0.001).Conclusion SP, CGRP, and VEGF expressions significantly increase in human dental pulps when stimulated by occlusal trauma combined with moderate orthodontic forces, as compared with these two stimuli applied independently. Name of the registry: Importance of Neurogenic Inflammation in the Angiogenic Response of the Dental Pulp as a Defensive ResponseTrial registration number: NCT03804034Date of registration: 01/15/2019 Retrospectively registeredURL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03804034?term=NCT03804034&draw=2&rank=1