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Horizontal root fracture (HRF) is a complex traumatic dental injury that affects the pulp, dentin, cementum, and periodontal ligament. This retrospective cohort study evaluated treatment outcomes in permanent teeth with HRF. We analyzed clinical and radiographic data from a dental trauma center (2006–2022). Permanent teeth with HRF with a follow up of ≥12 weeks were considered for outcome assessment (defined as clinical normalcy and radiographic healing at the fracture line). Prognostic factors were identified through multivariable logistic regression analyses (P value ≤.05). 125 teeth from 103 patients were included. After a median follow-up of 79 weeks, the overall favorable outcome was 92%. This includes teeth that received emergency splinting/repositioning at baseline (62.2%) and those that received subsequent endodontic intervention for the coronal fragment (baseline: 85%; subsequent follow-ups: 91.8%). Being male and incomplete root development were both significantly associated with a better outcome of splinting/repositioning (OR = 2.58; 95% CI, 1.06-6.24 and OR = 4.37; 95% CI, 1.16-16.41, respectively) and a reduced likelihood of requiring endodontic treatment (OR = 0.44; 95% CI, 0.20-0.96 and OR = 0.24; 95% CI, 0.08-0.76, respectively). Treatment delays surpassing one week were significantly associated with an increased likelihood of requiring endodontic treatment compared to timely presentations within 24 hours (OR = 3.06; 95% CI, 1.07-8.77; P value <.05). With timely diagnosis and treatment, and close monitoring, HRF cases can achieve a 92% favorable outcome. Male sex and incomplete root development correlate with improved baseline outcomes and a reduced need for endodontic treatment. Conversely, delayed presentation increases the likelihood of requiring endodontic intervention. [ABSTRACT FROM AUTHOR]

The efficacy and safety of a single novel electronic pulp sensitivity tester with a transilluminator (PSTT) capable of providing 4 different tests was compared with gold standard (GS) pulp testing methods. Four hundred eighty teeth, including 3 from each quadrant and their contralateral and opposing teeth, were randomly assessed using the PSTT or GS methods. Seven days later, the same teeth were assessed using the method not used earlier so that all teeth were evaluated using both methods. Sixty previously root canal–treated teeth, serving as negative controls, were assessed identically to the experimental groups. Results were analyzed using IBM SPSS software (IBM Corp, Armonk, NY) (P <.05). A higher percentage of teeth responded to cold and electricity using GS methods compared with the PSTT (99.4 vs 93.1 and 99.6 vs 97.3, respectively). A lower percentage of teeth responded to heat using the GS method compared with the PSTT (50.0 vs 68.1). Chi-square tests determined differences in the proportion of sensitivity to temperature, and electric testing methods were statistically significant (P <.001 and P =.004, respectively). No difference in the proportion of sensitivity was observed for transillumination. The Wilcoxon signed rank test determined significantly shorter cold testing times using the GS method (P =.024). Shorter testing times were observed using the PSTT for heat (P <.001), electric pulp testing (P =.048), and transillumination (P =.001). The overall PSTT testing time was significantly shorter than the GS testing time (P =.03). Tissue injury was not observed. The PSTT efficiently and safely provided heat and transillumination for pulpal diagnosis. Improvements are needed to enhance the cold and electric stimulus efficacy. [ABSTRACT FROM AUTHOR]

In young individuals, deciduous tooth pulp might be used as a natural, biologic scaffold for the regenerative endodontic treatment (RET) of young permanent teeth with necrotic pulps and apical periodontitis. The present case series demonstrates the clinical and radiographic outcomes of a novel RET using deciduous pulp autotransplantation in traumatized, necrotic young permanent incisors. Five previously traumatized maxillary incisors of four 8- to 11.5-year-old patients were treated with a RET protocol that used 2.5% NaOCl irrigation and placement of calcium hydroxide dressing in the first visit. After 4 weeks, the intracanal medication was removed, and the whole pulp tissue harvested from the neighboring maxillary deciduous canine was transplanted into the disinfected root canal without induced apical bleeding. Following placement of a mineral trioxide aggregate coronal barrier, the access cavities were restored with acid-etch resin composite. The root canals of donor primary canines were filled with calcium hydroxide-iodoform paste and were restored as with the permanent incisors. Three patients were followed-up for 24 months, and 1 patient for 12 months. All teeth demonstrated radiographic evidence of complete periapical healing, slight increase in dentinal wall thickness, and continued apical closure in the absence of clinical symptoms. A positive response to cold test was obtained in 1 incisor at 12 months and 2 at 24 months. Based on 12- and 24-month clinical and radiographic findings, the present cases demonstrate a favorable outcome of a RET protocol using deciduous pulp autotransplantation in young permanent incisors with pulp necrosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a novel method of endodontic therapy, which we refer to as dental pulp autotransplantation. Three patients (2 males and 1 female) were selected for endodontic treatment of a uniradicular premolar and extraction of a third molar (without odontosection). Electric assessment of pulp vitality and computed tomographic imaging were undertaken followed by endodontic access and instrumentation using triantibiotic solution for irrigation in the host tooth. A few minutes before the transplant procedure, the third molar was extracted, the tooth was sectioned with a diamond blade in a low-speed handpiece, and the pulp was carefully removed. After premolar instrumentation, the harvested and preserved pulp tissue was reinserted into the root canal followed by direct pulp capping performed using Biodentine (Septodont, Saint-Maur-des-Fossés, France), a liner of resin-modified glass ionomer cement and composite resin restoration. The teeth were followed up for at least 12 months after the procedures and were analyzed using computed tomographic imaging, electric pulp vitality testing, and Doppler ultrasound examination. At the 3- and 6-month follow-ups, positive pulp vitality and regression of periapical lesions were verified. After 9–12 months, all teeth were revascularized as determined by Doppler imaging, and the tooth vitality was reestablished with no signs of endodontic/periodontal radiolucency or complications. Within the limitations of the study, considering that it was a case series with only 3 patients, we described a highly innovative procedure of pulp autotransplantation, which appears to be feasible, highlighting the potential for clinical application of pulp regeneration using this new modality of endodontic therapy. [ABSTRACT FROM AUTHOR]

Transforming growth factor beta 1 (TGF-β1) is a key morphogen in regenerative endodontics; yet, its location within the hard tissue phase of dentin and its availability in mature roots have not been fully elucidated. Young mature (n = 8) and immature (n = 11) roots from sound premolars were obtained from 13 orthodontic patients aged 17 ± 1 and 12 ± 1 years, respectively. Roots were cleaned of organic remnants in 5% sodium hypochlorite. The width of the minor foramen was measured using a digital microscope. TGF-β1 distribution was assessed in 3 roots per group by immunostaining combined with confocal laser scanning microscopy. The root dentin of the remaining 13 roots was powdered and decalcified in 17% EDTA to determine the overall levels of hard tissue–embedded TGF-β1 by enzyme-linked immunosorbent assay. Data were compared between groups using the Student t test (α =.05). The minor foramen was 168 ± 49 μm versus 557 ± 295 μm in mature compared with immature roots (P <.05). TGF-β1 was highly stainable toward the pulp space in both groups. It was clearly associated with peritubular dentin and apparently absent in nontubular outer dentin. TGF-β1 content was 115 ± 31 pg and 74 ± 35 pg/100 mg mature versus immature root dentin, respectively (P >.05). TGF-β1 is deposited into the peritubular dentin. It should be possible to release this molecule in regenerative endodontic procedures from young mature roots as well as immature roots. [ABSTRACT FROM AUTHOR]

This study aimed to compare the cytocompatibility and angiogenic potential of 2 antibiotics (clindamycin [CLIN] and minocycline [MINO]) at distinct concentrations on dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs). DPSCs and HUVECs were exposed to cell culture media modified with CLIN or MINO at concentrations ranging from 30 μg/mL–1000 μg/mL. Cell toxicity and proliferation were investigated using the lactate dehydrogenase and tetrazolium reduction assays, respectively. A capillarylike tube formation in vitro assay was conducted to determine the angiogenic potential associated with each antibiotic. Additionally, selected morphometric angiogenesis parameters were determined using dedicated software (WimTube; Onimagin Technologies SCA, Córdoba, Spain). All statistical analyses were performed using 1-way analysis of variance and the Tukey post hoc test (α=.05). The collected data showed that compared with the control (cell culture media, alpha-minimum essential medium Eagle) increasing the antibiotic concentration significantly decreased cell viability and proliferation of both DPSCs and HUVECs. In terms of angiogenic potential, when tested at 30 μg/mL and 50 μg/mL, CLIN significantly amplified tube formation when compared with MINO with angiogenesis parameters (ie, tube length and tube number) similar to the effect promoted by exogenous vascular endothelial growth factor (50 ng/mL). CLIN was less cytotoxic when compared with MINO at higher concentrations. Of note, CLIN did not hinder the proangiogenic activity induced by vascular endothelial growth factor to the same extent as MINO, suggesting that the replacement of MINO by CLIN might translate into positive implications in the overall regenerative outcome. • Minocycline (MINO) and clindamycin (CLIN) displayed dose-dependent cytotoxicity. • CLIN is less cytotoxic when compared with MINO. • CLIN enhanced HUVEC proliferation and capillarylike tube formation. • CLIN (30 and 50 μg/mL) displayed angiogenic effects similar to exogenous VEGF. [ABSTRACT FROM AUTHOR]

Introduction Human dental pulp stem/progenitor cells (DPSCs) show remarkable regenerative potential in vivo . During regeneration, DPSCs may interact with their inflammatory environment via toll-like receptors (TLRs). The present study aimed to depict for the first time the TLR expression profile of DPSCs. Methods Cells were isolated from human dental pulp, STRO-1–immunomagnetically sorted, and seeded out to obtain single colony-forming units. DPSCs were characterized for CD14, CD34, CD45, CD73, CD90, CD105, and CD146 expression and for their multilineage differentiation potential. After incubation of DPSCs in basic or inflammatory medium (interleukin-1β, interferon-γ, interferon-α, tumor necrosis factor-α), TLR expression profiles were generated (DPSCs and DPSCs-i). Results DPSCs showed all characteristics of stem/progenitor cells. In basic medium DPSCs expressed TLRs 1–10 in different quantities. The inflammatory medium upregulated the expression of TLRs 2, 3, 4, 5, and 8, downregulated TLRs 1, 7, 9, and 10, and abolished TLR6. Conclusions The current study describes for the first time the distinctive TLR expression profile of DPSCs in uninflamed and inflamed conditions. [ABSTRACT FROM AUTHOR]

Introduction: The development of regenerative endodontic therapies offers exciting opportunities for future improvements in treatment outcomes. Methods: Advances in our understanding of regenerative events at the molecular and cellular levels are helping to underpin development of these therapies, although the various strategies differ in the translational challenges they pose. The identification of a variety of bioactive molecules, including growth factors, cytokines, chemokines, and matrix molecules, sequestered within dentin and dental pulp provides the opportunity to present key signaling molecules promoting reparative and regenerative events after injury. Results and Conclusions: The protection of the biological activity of these molecules by mineral in dentin before their release allows a continuing supply of these molecules, while avoiding the short half-life and the non-human origin of exogenous molecules. The ready release of these bioactive molecules by the various tissue preparation agents, medicaments, and materials commonly used in endodontics highlights the opportunities for translational regenerative strategies exploiting these molecules with little change to existing clinical practice. [ABSTRACT FROM AUTHOR]

Introduction A critical step in biomaterial selection effort is the determination of material as well as the biological properties of the target tissue. Previously, the selection of biomaterials and carriers for dental pulp regeneration has been solely based on empirical experience. Methods In this study, first, the linear viscoelastic material functions and compressive properties of miniature pig dental pulp were characterized using small-amplitude oscillatory shear and uniaxial compression at a constant rate. They were then compared with the properties of hydrogels (ie, agarose, alginate, and collagen) that are widely used in tissue regeneration. Results The comparisons of the linear viscoelastic material functions of the native pulp tissue with those of the 3 hydrogels revealed the gel-like behavior of the pulp tissue over a relatively large range of time scales (ie, over the frequency range of 0.1–100 rps). At the constant gelation agent concentration of 2%, the dynamic properties (ie, storage and loss moduli and the tanδ) of the collagen-based gel approached those of the native tissue. Under uniaxial compression, the peak normal stresses and compressive moduli of the agarose gel were similar to those of the native tissue, whereas alginate and collagen exhibited significantly lower compressive properties. Conclusions The linear viscoelastic and uniaxial compressive properties of the dental pulp tissue reported here should enable the more appropriate selection of biogels for dental pulp regeneration via the better tailoring of gelation agents and their concentrations to better mimic the dynamic and compressive properties of native pulp tissue. [ABSTRACT FROM AUTHOR]

Introduction Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)–mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. Methods Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm 3 , n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. Results Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly ( P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant ( P < .05) reduction in the percentage of viable bacteria compared with the negative control and PDS. Conclusions Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics. [ABSTRACT FROM AUTHOR]

Introduction Antibiotic-containing polymer-based nanofibers (hereafter referred to as scaffolds) have demonstrated great potential for their use in regenerative endodontics from both an antimicrobial and cytocompatibility perspective. This study sought to evaluate in vitro the effects of ciprofloxacin (CIP)-containing polymer scaffolds against Enterococcus faecalis biofilms. Methods Human mandibular incisors were longitudinally sectioned to prepare radicular dentin specimens. Sterile dentin specimens were distributed in 24-well plates and inoculated with E. faecalis for biofilm formation. Infected dentin specimens were exposed to 3 groups of scaffolds, namely polydioxanone (PDS) (control), PDS + 5 wt% CIP, and PDS + 25 wt% CIP for 2 days. Colony-forming units (CFU/mL) ( n = 10) and scanning electron microscopy (SEM) ( n = 2) were performed to quantitatively and qualitatively assess the antimicrobial effectiveness, respectively. Results PDS scaffold containing CIP at 25 wt% showed maximum bacteria elimination with no microbial growth, differing statistically ( P < .05) from the control (PDS) and from PDS scaffold containing CIP at 5 wt%. Statistical differences ( P < .05) were also seen for the CFU/mL data between pure PDS (5.92–6.02 log CFU/mL) and the PDS scaffold containing CIP at 5 wt% (5.39–5.87 log CFU/mL). SEM images revealed a greater concentration of bacteria on the middle third of the dentin specimen after 5 days of biofilm formation. On scaffold exposures, SEM images showed similar results when compared with the CFU/mL data. Dentin specimens exposed to PDS + 25 wt% CIP scaffolds displayed a practically bacteria-free surface. Conclusions On the basis of the data presented, newly developed antibiotic-containing electrospun scaffolds hold promise as an intracanal medicament to eliminate biofilm/infection before regenerative procedures. [ABSTRACT FROM AUTHOR]

Introduction Eliminating and/or inhibiting bacterial growth within the root canal system has been shown to play a key role in the regenerative outcome. The aim of this study was to synthesize and determine in vitro both the antimicrobial effectiveness and cytocompatibility of bimix antibiotic-containing polydioxanone-based polymer scaffolds. Methods Antibiotic-containing (metronidazole [MET] and ciprofloxacin [CIP]) polymer solutions (distinct antibiotic weight ratios) were spun into fibers as a potential mimic to the double antibiotic paste (DAP, a MET/CIP mixture). Fiber morphology, chemical characteristics, and tensile strength were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, and tensile testing, respectively. Antimicrobial efficacy was tested over time (aliquot collection) against Enterococcus faecalis (Ef), Porphyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn). Similarly, cytotoxicity was evaluated in human dental pulp stem cells. Data were statistically analyzed ( P < .05). Results Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed that electrospinning was able to produce antibiotic-containing fibers with a diameter mostly in the nanoscale. The tensile strength of 1:1MET/CIP scaffolds was significantly ( P < .05) higher than pure polydioxanone (control). Meanwhile, all other groups presented similar strength as the control. Aliquots obtained from antibiotic-containing scaffolds inhibited the growth of Ef, Pg, and Fn, except pure MET, which did not show an inhibitory action toward Pg or Fn. Antibiotic-containing aliquots promoted slight human dental pulp stem cell viability reduction, but none of them were considered to be cytotoxic. Conclusions Our data suggest that the incorporation of multiple antibiotics within a nanofibrous scaffold holds great potential toward the development of a drug delivery system for regenerative endodontics. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The aim of this investigation was to evaluate and compare the pulp stump wounds created by the following root canal instruments: ProFile rotary files and small-diameter fine diamond burs. Methods: Extracted mandibular premolars from adult patients with vital pulps and fully formed root canals were collected and stored in formalin. Within 48 hours of extraction, the periapical tissue was fixated to the root with a double coating of ethyl cyanoacrylate, and the pulp chambers were accessed with a #4 round carbide bur and high-speed handpiece in a traditional fashion. The pulp tissue of 10 specimens per group was extirpated at a level approximately 5 mm from the apex by using standard endodontic techniques. The specimens were then examined at ×100 magnification under a digital microscope. Grading criteria were developed, and the wounds were scored. Results: Wounds created by diamond burs were significantly smoother that those created by ProFile rotary files; the mean wound score for diamond burs was 1.4 versus a mean wound score of 3 for ProFiles. After the author's scoring of the wounds, 2 endodontist graders were shown photos of each specimen in a double-blind fashion and instructed to score each specimen as being smooth or rough. To validate the developed scoring system and remove potential observer bias of the author, the data from the double-blind observations were used to complete a cross-tabulation for a Cohen kappa test. Conclusions: Kappa values demonstrated substantial inter-rater agreement for both groups. [Copyright &y& Elsevier]

Abstract: Introduction: In pulpless immature human premolars implanted in rodents, this study investigated whether fibrin gel offered advantages over leaving the root canal empty regarding soft tissue ingrowth and cell differentiation. Methods: Root canals of extracted human immature premolars (n = 12) were accessed and then irrigated with 5% sodium hypochlorite followed by 17% ethylenediaminetetraacetic acid. Root canals were then either left empty or filled with a fibrin gel (n = 6 each) before being placed subcutaneously on top of the calvarial bone of rats (1 tooth per rat) for 12 weeks. After sacrifice, teeth were histologically assessed. Tissue ingrowth was quantified and compared between groups using the Mann-Whitney U test (P < .05). Cells adhering to the pulp canal wall were immunohistochemically screened for the presence of bone sialoprotein (BSP) and dentin sialoprotein (DSP). Results: More tissue grew into the pulp space when teeth were filled with fibrin gel (P < .05). The presence of fibrin gel affected not only the extent of tissue ingrowth but also tissue morphology and differentiation of cells contacting the dentinal wall. In the fibrin gel group, newly formed tissue was similar to normal pulp, constituted of inner pulp, cell-rich zone, cell-free zone, and an apparent odontoblast layer, which stained positive for BSP and DSP. Newly formed blood vessels were also more abundant compared with the initially empty root canals. Conclusions: Under the conditions of this study, fibrin gel improved cell infiltration and cell-dentin interaction. Both are necessary for pulp tissue regeneration. [Copyright &y& Elsevier]

Abstract: Introduction: Methacrylate resin–based materials could release components into adjacent environment even after polymerization. The major components leached include triethylene glycol dimethacrylate (TEGDMA). TEGDMA has been shown to induce the expression of cyclooxygenase-2 (COX-2). However, the mechanisms are not completely understood. The aims of this study were to investigate the molecular mechanism underlying TEGDMA-induced COX-2 in 2 oral cell types, the primary culture of human dental pulp (HDP) cells and the human embryonic palatal mesenchymal (HEPM) pre-osteoblasts, and to propose potential strategy to prevent or ameliorate the TEGDMA-induced inflammation in oral tissues. Methods: TEGDMA-induced COX-2 expression and its signaling pathways were assessed by Western blot analyses in HDP and HEPM cells. The inhibition of TEGDMA-induced COX-2 protein expression using various dietary phytochemicals was investigated. Results: COX-2 protein expression was increased after exposure to TEGDMA at concentrations as low as 5 μmol/L. TEGDMA-induced COX-2 expression was associated with reaction oxygen species, the extracellular signal-regulated kinase 1/2, and the p38 mitogen-activated protein kinase signaling pathways in HDP and HEPM cells. The activation of p38 mitogen-activated protein kinase was directly associated with reactive oxygen species. Epigallocatechin-3-gallate suppressed TEGDMA-induced COX-2 expression by inhibiting phosphorylation of extracellular signal-regulated kinase 1/2. Conclusions: Cells exposed to low concentrations of TEGDMA may induce inflammatory responses of the adjacent tissues, and this should be taken into consideration during common dental practice. Green tea, which has a long history of safe beverage consumption, may be a useful agent for the prevention or treatment of TEGDMA-induced inflammation in oral tissues. [Copyright &y& Elsevier]

Abstract: Introduction: 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are the first-line pharmaceuticals for the prevention and treatment of dyslipidemia. A recent investigation has shown that statins induced odontoblastic differentiation of dental pulp stem cells. Statins enhance the differentiation of human dental pulp cells by up-regulating mineralization nodules and odontogenic markers. This study tested the hypothesis that the systemic administration of statins results in increased dental pulp calcification. Methods: This retrospective case-control study used digital bitewing radiographs of mandibular molars. Subjects (N = 90) aged ≥60 years were assigned to either test (n = 45) or control (n = 45) groups based on the systemic use of statins. The dimensions of the pulp chambers were measured using a standardized method for height and mesiodistal distances. The chi-square test was used to analyze the data. Multiple linear regression model analysis was performed to explore the association between statin intake and pulp calcification. Results: Three of the 45 mandibular molars in the test group exhibited almost complete pulp chamber obliteration. There was a significant reduction in pulp chamber height ratio shown in the statin group compared with the control group (P < .0001). When the mesiodistal width was compared between the 2 groups, there was no significant difference (P = .3730). Conclusions: The significant increase of calcification and loss of vertical height of the pulp chamber observed in mandibular molars in patients on statin medication indicated a possible increased odontoblastic activity. Therefore, systemic statins could be a contributing factor for pulp chamber calcification. [Copyright &y& Elsevier]

Abstract: Introduction: MicroRNAs are small noncoding RNAs that play crucial roles in regulating normal and pathologic functions. Bacterial lipopolysaccharide (LPS) is one of the key regulators of pulpal pathogenesis. This study investigated how LPS regulates microRNA expression and affects the phenotype of human dental pulp cells (DPCs). Methods: Primary DPCs were established and immortalized to achieve immortalized DPCs (I-DPCs). DPCs and I-DPCs were treated with LPS and examined to identify changes in microRNA expression, cell proliferation, and cell migration. Quantitative reverse-transcriptase polymerase chain reaction was used to detect changes in gene expression. Exogenous miR-146a expression was performed transfection with pre-mir-146a mimic. Knockdown of interleukin receptor–associated kinase (IRAK1) and tumor necrosis factor receptor–associated factor 6 (TRAF6) expression was performed by small interference oligonucleotide transfection. Western blot analysis was used to detect changes in the expression of the IRAK1 and TRAF6 proteins. Results: The differentiation of DPCs was induced by osteogenic medium. I-DPCs had a higher level of human telomerase reverse transcriptase gene than the parental DPCs. Up-regulation of miR-146a expression and an increase in migration was induced by LPS treatment of DPCs and I-DPCs. Exogenous miR-146a expression increased the migration of DPCs and I-DPCs and down-regulated the expression of IRAK1 and TRAF6. Knockdown of IRAK1 and/or TRAF6 increased the migration of DPCs. Conclusions: The results suggested that LPS is able to increase the migration of DPCs by modulating the miR-146a–TRAF6/IRAK1 regulatory cascade. [Copyright &y& Elsevier]

Abstract: Introduction: The revitalization of a previously necrotic pulp space has been shown to be possible and even considered predictable. However, exact criteria for success are still lacking, and, in fact, some cases do not respond as predicted. Methods: In this case, the same operator treated 2 teeth similarly according to the principles laid out by Banch and Trope. The tooth that according to our expectations was more likely to be revitalized successfully failed to do so, whereas the second tooth that, in our estimation, was less likely to succeed was successful. In the tooth that failed to revitalize, auto-apexification occurred. Conclusions: Complete understanding for the criteria for predictable revitalization and apexification is still lacking. [Copyright &y& Elsevier]

Abstract: Introduction: Clinical dentistry is in need of noninvasive and accurate diagnostic methods to better evaluate dental pathosis. The purpose of this work was to assess the feasibility of a recently developed magnetic resonance imaging (MRI) technique, called SWeep Imaging with Fourier Transform (SWIFT), to visualize dental tissues. Methods: Three in vitro teeth, representing a limited range of clinical conditions of interest, imaged using a 9.4T system with scanning times ranging from 100 seconds to 25 minutes. In vivo imaging of a subject was performed using a 4T system with a 10-minute scanning time. SWIFT images were compared with traditional two-dimensional radiographs, three-dimensional cone-beam computed tomography (CBCT) scanning, gradient-echo MRI technique, and histological sections. Results: A resolution of 100 μm was obtained from in vitro teeth. SWIFT also identified the presence and extent of dental caries and fine structures of the teeth, including cracks and accessory canals, which are not visible with existing clinical radiography techniques. Intraoral positioning of the radiofrequency coil produced initial images of multiple adjacent teeth at a resolution of 400 μm. Conclusions: SWIFT MRI offers simultaneous three-dimensional hard- and soft-tissue imaging of teeth without the use of ionizing radiation. Furthermore, it has the potential to image minute dental structures within clinically relevant scanning times. This technology has implications for endodontists because it offers a potential method to longitudinally evaluate teeth where pulp and root structures have been regenerated. [Copyright &y& Elsevier]

Abstract: The success of regenerative endodontic procedures requires practitioner acceptance, but little or no evidence is available. The purpose of this survey was to collect the opinions of attendee''s of the 2008 Endodontic Board of Diplomates 2008 Summer Conference on the issue of regenerative endodontic procedures (REPs). After Nova Southeastern University institutional review board approval, 100 copies of a survey were circulated, and 56 completed surveys were returned anonymously. The survey found that 96% of participants thought that more regenerative therapies should be incorporated into treatments. Although only 14% of participants had used umbilical cord or stem cell banking for themselves or a relative, 63% thought that stem cell banking would be useful to regenerate dental tissues. Most (89%) of the participants would be willing to save teeth and dental tissues for stem cell banking. These results suggest that endodontic practitioners are supportive and optimistic about the future use of REPs. [Copyright &y& Elsevier]

Abstract: Tests relying on the passage of light through a tooth have been considered to be a suitable means of assessing vascularity and pulp vitality. Pulse oximetry is an effective, objective oxygen saturation monitoring technique broadly used in medicine for recording blood oxygen saturation levels. It can also be used in endodontic diagnosis for differential diagnosis of vital pulps and necrotic ones. In pulse oximetry, light is passed from a photoelectric diode across the tooth structure into a receptor. The instrument detects changes in absorption in both red and infrared light caused by alteration in tissue volume (tissue perfusion) during the cardiac cycle. However, there are some limitations inherent in the technology of pulse oximetry, such as the effect of increased acidity and metabolic rate, which cause deoxygenating of hemoglobin and changes in the blood oxygen saturation. Also, movements of the body or probe can complicate readings. Because this test produces no noxious stimuli, apprehensive or distressed patients may accept it more readily than routine methods. A review of the literature and a discussion of the potential application of this system in endodontics are presented. [Copyright &y& Elsevier]

Abstract: Corticotropin-releasing factor (CRF) binds to membrane-bound CRF receptors (CRF-Rs). Among the actions mediated by activated CRF-Rs is β-endorphin (END) release from immune cells, increasing peripheral antinociception. For assessment of inflammatory regulation of CRF-R expression, rats underwent pulp exposure of left, first mandibular molars and recovered for 6 days. Control pulpal tissue consisted of contralateral, uninjured molars and left, first mandibular molars of uninjured animals. Pulp tissue specimens were incubated with antibodies directed against CRF-R (both isoforms), neurofilament, CD45, and END. We observed (1) increases in pulp CRF-R immunoreactivity after injury, (2) increased CRF-R immunoreactivity expressed in 3 distinct zones in relation to the injury, and (3) increased CD45 and END immunoreactivity in regions surrounding the pulpal abscess. CRF-Rs might provide an additional target for novel analgesics to treat pulpal pain. [Copyright &y& Elsevier]

Abstract: There is a higher incidence of local anesthetic failure in endodontic patients experiencing pulpal hyperalgesia. Up-regulation of Nav1.9, a voltage-gated sodium channel isoform, might play a key role in local anesthetic failure because Nav1.9 channels increase neuronal excitability and have low sensitivity to blockade by local anesthetics. Immunocytochemistry was used to examine Nav1.9 channel expression in axons of symptomatic (painful) versus asymptomatic human dental pulp and to determine Nav1.9 expression levels in neuronal somata of the human trigeminal ganglion. Nav1.9 channel immunoreactivity on pulpal axons was significantly increased in painful teeth. Nav1.9 channels were expressed in membranes and cytoplasm of human trigeminal ganglion neurons, with the highest expression in small neuronal somata. Nav1.9 expression in the trigeminal ganglion coupled with increased expression in symptomatic pulp might contribute to hypersensitivity of inflamed pulps and local anesthetic failure. Furthermore, the present study suggests that Nav1.9 channels are potential targets for novel anesthetics. [Copyright &y& Elsevier]

Abstract: Pulpitis pain might be triggered by a cold stimulus, yet the cellular mechanisms responsible for this phenomenon are largely unknown. One possible mechanism involves the direct activation of cold-responsive thermoreceptors. The purpose of this study was to evaluate the possible role of the TRPM8 thermoreceptor in cold-mediated noxious pulpal pain mechanisms by comparing expression patterns in pulpal nerves from healthy control molars to cold-sensitive painful molars with irreversible pulpitis. Samples were identically processed with the indirect immunofluorescence method, and images were obtained with confocal microscopy. The immunofluorescence intensity and area occupied by TRPM8 within N52/PGP9.5-identified nerve fibers were quantified. Results showed that relative to normal samples, TRPM8 nerve area expression was significantly less in the cold-sensitive painful samples (34.9% vs 8%, P <0.03), but with no significant difference in immunofluorescence intensity between the 2 groups. These results suggest that TRPM8 is most likely not involved in cold-mediated noxious pulpal pain mechanisms. [Copyright &y& Elsevier]

Abstract: Transient receptor potential (TRP) channels function in diverse processes such as acting as second messenger systems, regulating of ionic concentrations, and aiding in thermoception. TRPM2 channels, members of the melastatin subfamily, mediate calcium influx in response to oxidative stress but during pathological states facilitate hyperexcitability and cellular necrosis via calcium excitotoxicity. We hypothesized that TRPM2 channel expression is upregulated in pulpal tissue of symptomatic teeth with signs of irreversible pulpitis. TRPM2 channel expression was significantly increased in pulp from clinically diagnosed symptomatic teeth compared with pulp from asymptomatic teeth. Additionally, increased TRPM2 expression in symptomatic pulp was the result of increased immunoreactivity in fibroblasts, whereas neural expression of TRPM2 was absent. We provide a possible mechanism explaining the association between TRPM2 channel expression with pain and necrosis. We suggest that TRPM2 channel antagonists could be administered in attempts to inhibit the progression of or even reverse pulpal degradation. [Copyright &y& Elsevier]

Abstract: The aim of this in vitro study was to measure key morphological features of pulp chambers from furcated maxillary bicuspid teeth. There were 107 random human maxillary bicuspid teeth used. Each bicuspid was radiographed using the Trophy RVG digital imaging system and a Belmont Acuray X-ray at 70 kVp. Measurements were made using the Digipan measuring mode of the Trophy system. Results were mean (mm): pulp chamber floor to furcation: 1.85 ± 0.85; pulp chamber ceiling to furcation: 4.61 ± 1.04; cusp to furcation: 11.55 ± 1.12; cusp to pulp chamber ceiling: 6.94 ± 0.70; pulp chamber height: 2.76 ± 0.97. The measurements showing the lowest percentage variance were: cusp to furcation (9.70%) and cusp to pulp chamber ceiling (10.09%). The only measurement that was statistically the same across maxillary molars, mandibular molars and bicuspids was measurement “B,” pulp chamber ceiling to furcation. The critical distance from cusp tip to pulp chamber ceiling in bicuspids was approximately 7.00 mm. [Copyright &y& Elsevier]

Abstract: Kv1.4, a subunit of voltage-gated K+ channels, plays a large role in regulating neuronal excitability. The level of Kv1.4 expression is unknown in human sensory neurons innervating healthy or painful tissue. Therefore, we examined Kv1.4 immunoreactivity in axons innervating both clinically diagnosed asymptomatic and painful symptomatic human tooth pulp. Antibodies directed against Kv1.4 and PGP9.5, a protein marker for axons, was used to determine the proportion of PGP9.5 immunopositive tissue that was also immunopositive for Kv1.4. We report that on pulpal axons innervating symptomatic teeth Kv1.4 immunoreactivity, a correlate of decreased Kv1.4 expression, is significantly decreased (p < 0.0001), suggestive of a factor responsible for facilitating chronic dental pain and decreases in currents produced, such as IA, in neurons innervating painful pulp. [Copyright &y& Elsevier]

Odontoblasts produce dentin throughout life and in response to trauma. The purpose of this study was to identify the roles of endogenous Wnt signaling in regulating the rate of dentin accumulation. Histology, immunohistochemistry, vital dye labeling, and histomorphometric assays were used to quantify the rate of dentin accumulation as a function of age. Two strains of Wnt reporter mice were used to identify and follow the distribution and number of Wnt-responsive odontoblasts as a function of age. To show a causal relationship between dentin secretion and Wnt signaling, dentin accumulation was monitored in a strain of mice in which Wnt signaling was aberrantly elevated. Dentin deposition occurs throughout life, but the rate of accumulation slows with age. This decline in dentin secretion correlates with a decrease in endogenous Wnt signaling. In a genetically modified strain of mice, instead of tubular dentin, aberrantly elevated Wnt signaling resulted in accumulation of reparative dentin or osteodentin secreted from predontoblasts. Wnt signaling regulates dentin secretion by odontoblasts, and the formation of reparative or osteodentin is the direct consequence of elevated Wnt signaling. These preclinical data have therapeutic implications for the development of a biologically based pulp capping medicant. [ABSTRACT FROM AUTHOR]

The elimination of microbial flora in cases of immature permanent teeth with necrotic pulp is both key and a challenging goal for the long-term success of regenerative therapy. Recent research has focused on the development of cell-friendly intracanal drug delivery systems. This in vitro study aimed to investigate the antimicrobial action of 3-dimensional (3D) tubular-shaped triple antibiotic–eluting nanofibrous constructs against a multispecies biofilm on human dentin. Polydioxanone polymer solutions, antibiotic-free or incorporated with metronidazole, ciprofloxacin, and minocycline, were electrospun into 3D tubular-shaped constructs. A multispecies biofilm consisting of Actinomyces naeslundii , Streptococcus sanguinis , and Enterococcus faecalis was forced inside the dentinal tubules via centrifugation in a dentin slice in vitro model. The infected specimens were exposed to 2 experimental groups (ie, 3D tubular-shaped triple antibiotic–eluting constructs and triple antibiotic paste [TAP]) and 2 control groups (7-day biofilm untreated and antibiotic-free 3D tubular-shaped constructs). Biofilm elimination was quantitatively analyzed with confocal laser scanning microscopy. Confocal laser scanning microscopic (CLSM) analysis showed a dense population of viable (green) bacteria adhered to dentin and penetrated into the dentinal tubules. Upon 3D tubular-shaped triple antibiotic–eluting nanofibrous construct exposure, nearly complete elimination of viable bacteria on the dentin surface and inside the dentinal tubules was shown in the CLSM images, which was similar ( P < .05) to the bacterial death promoted by the TAP group but significantly greater when compared with both the antibiotic-free 3D tubular-shaped constructs and the control (saline). The proposed 3D tubular-shaped antibiotic-eluting construct showed pronounced antimicrobial effects against the multispecies biofilm tested and therefore holds significant clinical potential as a disinfection strategy before regenerative endodontics. [ABSTRACT FROM AUTHOR]

Pulp regeneration and its clinical translation into regenerative endodontic procedures are receiving increasing research attention, leading to significant growth of the published scientific and clinical literature within these areas. Development of research strategies, which consider patient-, clinician-, and scientist-based outcomes, will allow greater focus on key research questions driving more rapid clinical translation. Three key areas of focus for these research questions should include cells, signaling, and infection/inflammation. A translational pathway is envisaged in which clinical approaches are increasingly refined to provide regenerative endodontic protocols that are based on a robust understanding of the physiological processes and events responsible for the normal secretion, structure, and biological behavior of pulpal tissue. [ABSTRACT FROM AUTHOR]

The balance between the immune/inflammatory and regenerative responses in the diseased pulp is central to the clinical outcome, and this response is unique within the body because of its tissue site. Cariogenic bacteria invade the dentin and pulp tissues, triggering molecular and cellular events dependent on the disease stage. At the early onset, odontoblasts respond to bacterial components in an attempt to protect the tooth's hard and soft tissues and limit disease progression. However, as disease advances, the odontoblasts die, and cells central to the pulp core, including resident immune cells, pulpal fibroblasts, endothelial cells, and stem cells, respond to the bacterial challenge via their expression of a range of pattern recognition receptors that identify pathogen-associated molecular patterns. Subsequently, recruitment and activation occurs of a range of immune cell types, including neutrophils, macrophages, and T and B cells, which are attracted to the diseased site by cytokine/chemokine chemotactic gradients initially generated by resident pulpal cells. Although these cells aim to disinfect the tooth, their extravasation, migration, and antibacterial activity (eg, release of reactive oxygen species [ROS]) along with the bacterial toxins cause pulp damage and impede tissue regeneration processes. Recently, a novel bacterial killing mechanism termed neutrophil extracellular traps (NETs) has also been described that uses ROS signaling and results in cellular DNA extrusion. The NETs are decorated with antimicrobial peptides (AMPs), and their interaction with bacteria results in microbial entrapment and death. Recent data show that NETs can be stimulated by bacteria associated with endodontic infections, and they may be present in inflamed pulp tissue. Interestingly, some bacteria associated with pulpal infections express deoxyribonuclease enzymes, which may enable their evasion of NETs. Furthermore, although NETs aim to localize and kill invading bacteria using AMPs and histones, limiting the spread of the infection, data also indicate that NETs can exacerbate inflammation and their components are cytotoxic. This review considers the potential role of NETs within pulpal infections and how these structures may influence the pulp's vitality and regenerative responses. [ABSTRACT FROM AUTHOR]

Dental tissue infection and disease result in acute and chronic activation of the innate immune response, which is mediated by molecular and cellular signaling. Different cell types within the dentin-pulp complex are able to detect invading bacteria at all stages of the infection. Indeed, at relatively early disease stages, odontoblasts will respond to bacterial components, and as the disease progresses, core pulpal cells including fibroblasts, stems cells, endothelial cells, and immune cells will become involved. Pattern recognition receptors, such as Toll-like receptors expressed on these cell types, are responsible for detecting bacterial components, and their ligand binding leads to the activation of the nuclear factor-kappa B and p38 mitogen-activated protein (MAP) kinase intracellular signaling cascades. Subsequent nuclear translocation of the transcription factor subunits from these pathways will lead to proinflammatory mediator expression, including increases in cytokines and chemokines, which trigger host cellular defense mechanisms. The complex molecular signaling will result in the recruitment of immune system cells targeted at combating the invading microbes; however, the trafficking and antibacterial activity of these cells can lead to collateral tissue damage. Recent evidence suggests that if inflammation is resolved relatively low levels of proinflammatory mediators may promote tissue repair, whereas if chronic inflammation ensues repair mechanisms become inhibited. Thus, the effects of mediators are temporal context dependent. Although containment and removal of the infection are keys to enable dental tissue repair, it is feasible that the development of anti-inflammatory and immunomodulatory approaches, based on molecular, epigenetic, and photobiomodulatory technologies, may also be beneficial for future endodontic treatments. [ABSTRACT FROM AUTHOR]

Abstract: Various treatment concepts have been suggested to solve the deep carious lesion dilemma. Recent systematic reviews are presented. Their conclusions are based on very few studies, and the main message is that optimal randomized clinical studies are lacking. Observational studies on indirect pulp treatment and stepwise excavation demonstrate that these treatments avoid pulp exposures, but it cannot be said which approach is best. A less invasive modified stepwise excavation approach is described, focusing on changing an active lesion into an arrested lesion even without performing an excavation close to the pulp. In Denmark and Sweden a randomized clinical multi-center trial is currently taking place, the Caries and Pulp (CAP) trial. This trial is investigating the effects of stepwise excavation over 2 visits versus 1 complete excavation of deep caries in permanent teeth. Guidelines for treatment are presented. [Copyright &y& Elsevier]

Abstract: The regenerative potential of dental pulp, particularly in mature teeth, has been considered extremely limited. However, our improved understanding of pulpal inflammation and repair and improved dental materials and technologies make vital pulp therapy a viable alternative to root canal treatment. This article explores our knowledge in this regard and the future potential of saving or even regenerating the pulp as a routine dental procedure. [Copyright &y& Elsevier]

Abstract: The literature is almost devoid of scientific studies of diagnosis of pulpal pathology in primary and permanent teeth with open apices. Most reports are empirical or retrospective studies without adequate prior knowledge of preexisting conditions or histologic findings leading to the necessity of pulpal procedures. Appropriate diagnostic tests and their effectiveness are documented for both groups. This article reviews the available literature and current techniques of indirect pulp therapy, pulp capping, and pulpotomy for primary teeth and permanent teeth with open apex. The apical barrier with mineral trioxide aggregate followed by root strengthening with bonded composite is reviewed. [Copyright &y& Elsevier]