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This study aimed to comparatively assess the clinical success and radiographic regenerative dentin formation of Platelet Rich Fibrin (PRF) and mineral trioxide aggregate (MTA) when used as direct pulp capping agents. This double-blinded two parallel armed randomized controlled clinical trial comprised the allocation of 108 patients with traumatically exposed dental pulp during the management of deep carious lesions by undergraduate students after fulfilling inclusion and exclusion criteria. Patients were randomized into two groups ( n  = 54 in each group) using computer-generated simple randomization, wherein one group Platelet Rich Fibrin (PRF) was prepared from patients’ blood samples and applied directly over exposed pulp followed by MTA application and in the other group MTA was applied directly over pulp exposure. In both groups, cavities were restored with resin-modified glass ionomer liner and resin composite restoration. The overall success of treatment was calculated at 6 and 12 months after assessing pulp sensibility, history of pain, tenderness on percussion and the existence of any periapical pathosis using in periapical radiographs. Moreover CBCT was used at 12 months to determine the presence or absence of dentin bridge as a secondary outcome. After 12 months follow-up, there was no statistically significant difference in overall success of pulp capping in both groups. As the both groups showed 92.59% success rate. CBCT evaluation of dentin bridge formation by Platelet Rich Fibrin (PRF) demonstrated a significantly higher percentage than that formed in cases treated with MTA alone ( p  < 0.001). Direct pulp capping with Platelet Rich Fibrin (PRF) exhibited a clinical and radiographic success rate comparable to that of MTA. Platelet Rich Fibrin (PRF) can be implemented as a direct pulp capping agent in forthcoming clinical applications.

This study aimed to evaluate the histological short-term response of intact premolars following direct pulp capping (DPC) using four bioactive materials: Neo MTA Plus (NMP), Neo Putty (NP), Total Fill BC Fast set putty (FSP), and Total Fill BC RRM Paste (BCP). Thirty-two intact premolars in eight patients scheduled for orthodontic extraction were included. Teeth were randomly assigned into four groups based on the bioactive material applied during pulpotomy. Each patient will experience the four direct pulp capping materials, randomly assigned to their four premolars: NMP group (n = 8), NP group (n = 8), FSP group (n = 8), and BCP group (n = 8). Premolars were extracted after four weeks. Histological evaluations assessed pulpal inflammation intensity (PII) and dentinal bridge continuity (DBC). Kruskal–Walis and Mann–Whitney U tests were used to analyze the data. Statistical significance was set at α = 0.05. There were significant differences in the PII among groups ( p  = 0.001). The NMP group was lower than the other three material groups (NP, FSP, and BCP). Moreover, there were significant differences in the DBC among groups ( p  < 0.001). DBC in the NMP group was lower than that of the other three material groups (NP, FSP, and BCP). Additionally, the DBC in the FSP group was higher than in the NP and BCP groups. The short-term histological examination suggests that the NMP group exhibited the lowest PII but was associated with inferior continuity of the formed dentin bridge. In contrast, the FSP group demonstrated superior continuity of the formed dentin bridge.

The ultimate goal of this study is to regenerate lost dental pulp and dentin via stem/progenitor cell–based approaches and tissue engineering technologies. In this study, we tested the possibility of regenerating vascularized human dental pulp in emptied root canal space and producing new dentin on existing dentinal walls using a stem/progenitor cell–mediated approach with a human root fragment and an immunocompromised mouse model. Stem/progenitor cells from apical papilla and dental pulp stem cells were isolated, characterized, seeded onto synthetic scaffolds consisting of poly-D,L-lactide/glycolide, inserted into the tooth fragments, and transplanted into mice. Our results showed that the root canal space was filled entirely by a pulp-like tissue with well-established vascularity. In addition, a continuous layer of dentin-like tissue was deposited onto the canal dentinal wall. This dentin-like structure appeared to be produced by a layer of newly formed odontoblast-like cells expressing dentin sialophosphoprotein, bone sialoprotein, alkaline phosphatase, and CD105. The cells in regenerated pulp-like tissue reacted positively to anti-human mitochondria antibodies, indicating their human origin. This study provides the first evidence showing that pulp-like tissue can be regenerated de novo in emptied root canal space by stem cells from apical papilla and dental pulp stem cells that give rise to odontoblast-like cells producing dentin-like tissue on existing dentinal walls.

Background Experiments have previously demonstrated the therapeutic potential of mobilized dental pulp stem cells (MDPSCs) for complete pulp regeneration. The aim of the present pilot clinical study is to assess the safety, potential efficacy, and feasibility of autologous transplantation of MDPSCs in pulpectomized teeth. Methods Five patients with irreversible pulpitis were enrolled and monitored for up to 24 weeks following MDPSC transplantation. The MDPSCs were isolated from discarded teeth and expanded based on good manufacturing practice (GMP). The quality of the MDPSCs at passages 9 or 10 was ascertained by karyotype analyses. The MDPSCs were transplanted with granulocyte colony-stimulating factor (G-CSF) in atelocollagen into pulpectomized teeth. Results The clinical and laboratory evaluations demonstrated no adverse events or toxicity. The electric pulp test (EPT) of the pulp at 4 weeks demonstrated a robust positive response. The signal intensity of magnetic resonance imaging (MRI) of the regenerated tissue in the root canal after 24 weeks was similar to that of normal dental pulp in the untreated control. Finally, cone beam computed tomography demonstrated functional dentin formation in three of the five patients. Conclusions Human MDPSCs are safe and efficacious for complete pulp regeneration in humans in this pilot clinical study.

Background With increasing studies being published on regenerative endodontic procedures (REPs) as a treatment modality for mature necrotic teeth, the assessment of outcomes following regenerative endodontic procedures has become more challenging and the demand for a better understanding of the regenerated tissues following this treatment is rising. The study aimed to correlate cold, electric pulp testing (EPT), and magnetic resonance imaging (MRI) signal intensity (SI) in mature necrotic teeth treated with regenerative endodontic procedures. Methodology This retrospective cohort study included eighteen adult patients who experienced tooth necrosis in mature maxillary anterior teeth recruited from the outpatient clinic, Conservative Dentistry Department, Faculty of Dentistry, Alexandria University, Alexandria, Egypt from July 2017 until December 2018 with 12 months of follow-up. regenerative endodontic procedures via blood clot were performed. The canals were instrumented by ProTaper Next (PTN) files until final sizes X3 or X5. Biodentine was used as cervical plug material. Pre and post-operative clinical follow-up was done where the patients’ responses to cold and electric pulp testing were given a scoring system and were compared to the normal contralateral tooth. Pre and post-operative magnetic resonance imaging signal intensity of both the involved tooth and its contralateral at the middle and the apical thirds of the root canals were assessed after 3, 6, and 12 months. Data was analyzed using the ANOVA, Friedman and Bonferroni tests. Significance was set at a p -value < 0.05. Results All 18 teeth scored a baseline score of “2” for cold and electric pulp testing. There was a significant difference between scores of the cold test at baseline and 12-month follow-up ( p  < 0.001). There was a significant difference between scores of the electric pulp testing of baseline and 12-month follow-up ( p  < 0.001). There was a moderately significant indirect (inverse) correlation between magnetic resonance imaging signal intensity and cold test in both the middle and apical thirds at 12 months. No significant correlations were detected between magnetic resonance imaging signal intensity and electric pulp testingat any of the time intervals ( p  > 0.05). Conclusion Magnetic resonance imaging is a successful non-invasive method to assess outcomes of regenerative endodontic procedures and correlating it with another reliable method of assessing pulpal responses, cold test, could validate these outcomes. Clinical trial registration The study was registered with ClinicalTrials.gov (ID: NCT03804450).

ObjectiveThis study aimed to evaluate the dental pulp responses to recombinant human erythropoietin (rhEPO) and/or mineral trioxide aggregate (MTA) in pulp capping of inflamed dental pulp in vivo.Materials and MethodsIn accordance with ARRIVE guidelines, pulp inflammation was induced by exposing the maxillary first molars (n = 64) of Wistar rats (n = 32) to the oral environment for two days. The exposed pulps were randomly assigned four groups based on the pulp capping material: rhEPO, MTA, MTA + rhEPO, or an inert membrane. An additional eight rats formed the healthy control group. After four weeks, the animals were euthanized, and histological, qRT-PCR, and spectrophotometric techniques were employed to analyze the left maxillary segments, right first maxillary molars, and blood samples, respectively. Statistical significance was set at p < 0.05 and < 0.001.ResultsPulp capping with rhEPO, MTA, or MTA + rhEPO resulted in lower inflammation and higher mineralization scores compared to untreated control. MTA + rhEPO group exhibited significantly decreased expression of tumor necrosis factor-alpha, and interleukin 1-beta, while MTA group showed substantially reduced expression of interferon-gamma. Both rhEPO and MTA + rhEPO groups presented elevated dentin matrix protein 1 levels compared to untreated control. Furthermore, pulp capping with rhEPO and/or MTA led to increased transforming growth factor-beta 1 expression and reductions of pro-inflammatory/immunoregulatory cytokine ratios and prooxidative markers. Pulp capping with rhEPO also resulted in increase of systemic antioxidative stress markers.ConclusionCapping with rhEPO or MTA + rhEPO resulted in a favorable effect that was similar or even superior to that of MTA.

Background Locating calcified canals in teeth with pulp canal obliteration remains particularly challenging. The absence of data from randomized controlled trials conducted in vivo has been a critical gap. The objective of this study was to comprehensively assess the accuracy of static-guided endodontics in addressing the challenges of pulp canal obliteration through a randomized controlled clinical trial, as well as pain during treatment and clinical outcomes. Methods Eighty patients with pulp canal obliteration were selected from July 2020 to March 2022 and randomly divided into two groups. In the freehand group, patients underwent contemporary freehand access cavity preparation. Patients in the static-guided group underwent innovative access cavity preparation using three-dimensional-printed endodontic guides for precise root canal localization. The quantitative accuracy was subsequently evaluated through meticulous assessment of indirect impression scans obtained from the access cavities. Moreover, pain during treatment and clinical outcome were investigated. Results All participants were randomly assigned to treatment groups. The static-guided group showed high accuracy, with average deviations of 0.14 ± 0.08 mm at the coronal entry point, 0.35 ± 0.16 mm at the apical point, and an angular deviation of 1.75 ± 0.30 °. These deviations were significantly lower than those in the freehand group ( P  < 0.0001). No significant difference were found between the groups regarding pain during treatment and clinical outcomes after one year ( P  > 0.05). Conclusion This study demonstrates, within its limitations, the static endodontics guides represent an accurate method in locating root canals for pulp canal obliteration through a randomized controlled clinical trial. Trial registration The Chinese Clinical Trial Registry, NO. ChiCTR2000037260 (27/08/2020, retrospectively registered).

The intra- and intercellular signaling molecule nitric oxide (NO) is produced in endothelial cells by the activity of endothelial NO synthase (eNOS). Upon formation, NO diffuses into the underlying vascular smooth muscle cells, where it activates NO-sensitive guanylyl cyclase (NO-GC) resulting in the production of cyclic guanosine 3′,5′-monophosphate (cGMP) from guanosine 5′-triphosphate (GTP). Inducing vasodilatation, inhibiting platelet aggregation and leukocyte adhesion, and inhibiting the proliferation and migration of vascular smooth muscle cells, the NO-cGMP signaling leads to a number of anti-inflammatory processes. Inflammation-dependent elevated concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in blood vessels of inflamed dental pulp induce an uncoupling of eNOS and oxidized NO-GC, leading to a disruption of NO-cGMP signaling. Endothelial dysfunction in inflamed dental pulp alters cell–cell and cell–matrix interactions, reducing the regenerative and reparative potential of the dentin–pulp complex in response to carious lesions. In the therapeutic management of caries, it is essential to consider the presence of endothelial dysfunction in the inflamed dental pulp. The utilization of NO-GC stimulators and activators in indirect and direct pulp capping materials may enhance the regeneration and repair potential of inflamed dental pulp.