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Bmi1 is a polycomb protein localized in stem cells and maintains their stemness. This protein is also reported to regulate the expression of various differentiation genes. In this study, to analyze the role of Bmi1 during dentinogenesis, we examined the immunohistochemical localization of Bmi1 during rat tooth development as well as after cavity preparation. Bmi1 localization was hardly detected in the dental mesenchyme at the bud and cap stages. After the bell stage, however, this protein became detectable in preodontoblasts and early odontoblasts just beginning dentin matrix secretion. As dentin formation progressed, Bmi1 immunoreactivity in the odontoblasts decreased in intensity. After cavity preparation, cells lining the dentin and some pulp cells under the cavity were immunopositive for Bmi1 at 4 days. Odontoblast-like cells forming reparative dentin were immunopositive for Bmi1 at 1 week, whereas their immunoreactivity was not detected after 8 weeks. We further analyzed the function of Bmi1 using KN-3 cells, a dental mesenchymal cell line. Overexpression of Bmi1 in KN-3 cells promoted mineralized tissue formation. In contrast, siRNA knockdown of Bmi1 in KN-3 cells reduced alkaline phosphatase activity and the expression of odontoblast differentiation marker genes such as Runx2, osterix, and osteocalcin. Additionally, KN-3 cells transfected with siRNA against Bmi1 showed reduced nuclear transition of β-catenin and expression of phosphorylated-Smad1/5/8. Taken together, these findings suggest that Bmi1 was localized in the odontoblast-lineage cells in their early differentiation stages. Bmi1 might positively regulate their differentiation by accelerating Wnt and BMP signaling pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND: Erythropoietin has anti-inflammatory, anti-apoptotic, and pro-bone defect repair effects. To date, fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE: To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS: (1) Animal experiment: Thirty-two rats were randomly divided into control group (n=16) and experimental group (n=16). In the experimental group, collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury, and in the control group, collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury. The cavity was then closed with glass ionomer adhesive. After 2 and 4 weeks of treatment, the maxillary bones of the two groups were collected, and the expression of nestin in dentin was detected by immunohistochemistry, and the reparative dentin production was observed by hematoxylin-eosin staining. The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth. (2) Cell experiment: Human dental pulp cells, human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue, periodontal ligament, and gingival tissue. Real-time reverse transcription PCR (RT-PCR) was used to detect the mRNA expression of erythropoietin. Erythropoietin, dentin sialophosphoprotein, dentin matrix protein 1, and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation. After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation, the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR, and the formation of mineralized nodules was detected by alizarin red S staining, and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot, respectively. RESULTS AND CONCLUSION: (1) Animal experiment: Compared with the control group, the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment. The expression of erythropoietin was weakly positive in pulp, odontoblastic cell layer and periodontal membrane of the rat’s first maxillary molar, and strongly positive in odontoblasts. (2) Cell experiment: The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells. The mRNA expressions of dentin sialophosphorin, dentin matrix protein 1, nestin, erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions. The mRNA expression of dentin sialophosphoprotein, dentin matrix protein 1, nestin, bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation, and the protein expression of bone morphogenetic protein 2 was also decreased. After exogenous erythropoietin intervention, the expression of the above indexes in human dental pulp cells increased. To conclude, erythropoietin can promote the formation of dentin to some extent. [ABSTRACT FROM AUTHOR]

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Objective To explore the effect of leukocyte-and platelet-rich fibrin (L-PRF) as a capping agent in the modulation of inflammation in rat dental pulp. Methods The rat model of pulpitis was established by lipopolysaccharide (LPS) . A total of 30 Sprague-Dawley rats were randomly divided into five groups: Normal control group, Model group, iRoot BP PLUS group, L-PRF group, iRoot BP PLUS+ L-PRF group. Samples were collected on the 14th day after pulp capping. Micro-CT scans, HE and Masson staining, qRT-PCR assays were performed to observe pulp tissue inflammatory and hard tissue formation. Results Micro-CT results: no hard tissue formation was seen in the LPS group, plaque calculus was seen in the L-PRF group, and a more complete calcified bridge was seen at the perforation of the pulp in the BP and combined groups, HE and Masson staining results: the LPS group had the most severe inflammation and no hard tissue formation, the combined group had the least inflammation and the most complete and continuous hard tissue formation, and there was a statistical difference between the two groups(P < 0.01), There was no statistical difference in the degree of inflammatory reaction and hard tissue formation between the BP group and the combined group (P > 0.05), qRT-PCR results: the relative expression levels of TNF-α, IL-1β, and IL-6 mRNA in the pulp tissues of all experimental groups were reduced compared with those of the LPS group, but the differences between the L-PRF and LPS groups were not statistically significant (P > 0.05) . Conclusion The combination of L-PRF and iRoot BP PLUS as a composite pulp capping material can be used for the repair of dental pulp tissue and the regulation of inflammation in dental pulpitis in rats. [ABSTRACT FROM AUTHOR]

Patients with type 1 diabetes mellitus (DM1) tend to have delayed wound healing, even in the pulp tissue. We hypothesized that hyperglycemia affects odontoblast-like cell (OLC) differentiation and is involved in macrophage polarization. Accordingly, we evaluated dental pulp stem cell differentiation and macrophage phenotypes after pulpotomy. After modifying DM1 rat models by streptozotocin, 8-week-old rats' upper left first molars were pulpotomized with mineral trioxide aggregate. Meanwhile, the control group was administered saline. Immunohistochemical localization of nestin, osteopontin, α-smooth muscles (α-SMAs), and CD68 (pan-macrophage marker) was conducted 7 days after pulpotomy. The OLC differentiation stage was determined using double immunofluorescence of nestin and α-SMA. Double immunofluorescence of CD68 and iNOS was counted as M1 macrophages and CD68 and CD206 as M2 macrophages. Proliferating cell nuclear antigen and Thy-1 (CD90) were evaluated by immunofluorescence. In DM1 rats, the reparative dentin bridge was not complete; however, the osteopontin-positive area did not differ significantly from that in controls. Proliferating cell nuclear antigen, indicative of cell proliferation, increased in positive cells in DM1 rats compared with controls. Double-positive cells for α-SMA and nestin indicated many immature OLCs in DM1. CD90 was positive only in controls. CD68-positive cells, especially M1 macrophages, were increased in DM1 rats, allowing the inflammatory stage to continue 7 days after pulpotomy. The condition of DM1 model rats can interfere at various stages of the wound healing process, altering OLC differentiation and macrophage polarization. These findings highlight the importance of normal blood glucose concentrations during pulp wound healing. [ABSTRACT FROM AUTHOR]

Abstract Background There is still a lack of knowledge regarding the permeability and configuration of infected root dentin. The aim of this ex vivo study was to compare the dentin penetrability of healthy teeth and necrotic teeth with apical periodontitis by evaluating the penetration of sodium hypochlorite (NaOCl) and to analyze the histopathological features of root dentin. Methods Forty-eight molars were collected and divided into two groups. The clinical diagnosis for one group was pulp necrosis with apical periodontitis and the pulp and periapex were normal in the other group. Forty-eight straight roots were divided into two groups: infected and healthy. First, all root canals were stained with 2% methylene blue to visualize penetration after standard root canal instrumentation and irrigation. Transverse sections were obtained, and the dye penetration parameters were measured. The cross sections were processed to 20–30 μm and stained with hematoxylin and eosin for observation of the histopathological changes in the root dentin. Results The maximum penetration depth, median penetration depth and penetration percentage of NaOCl solutions, in infected root canals were significantly lower than those in healthy root canals. The histopathological analysis showed that the frequency of reparative dentin formation in infected root canals was significantly greater than that in healthy root canals. Conclusions The dentin penetrability of teeth with necrotic teeth and apical periodontitis was more superficial during root canal irrigation than that of healthy teeth. The histopathological changes in infected radicular dentin, namely the formation of reparative dentin, might be associated with the lower permeability of dentin tubules in human teeth with apical periodontitis.

Direct pulp capping is performed to maintain the vitality of the exposed pulp by applying a dressing material to facilitate reparative dentinogenesis as a biological seal. Osteoporosis increases oxidative stress and inflammation therefore dentinogenesis was disrupted. Dentin bridge reparative produced by direct pulp capping material still inappropriate, there is a tunnel defect. Chitosan is a natural polysaccharide biopolymer, non-toxic, biocompatible, biodegradable, has broad spectrum antimicrobial properties, anti-inflammatory and antioxidant. OPN and RUNX2 secretion expressed by odontoblast-like cells can be a sign of reparative dentin formation in osteoporosis. The aim of this research to analyse the effect of calcium hydroxide and chitosan combination on the increased expression of OPN and RUNX2 on day 1, day 3 and day 6 in reparative dentin formation in osteoporosis. This experimental study using a total of 42 wistar rat. Ovariohysterectomy was performed to induced osteoporosis and verified by tunel assay after 3 months. Rats divided into 6 groups, the control group on day 1, day 3 and day 6, the treatment group on day 1, day 3 and day 6. Necropsy was performed and teeth samples were obtained. After being decalcified, specimens underwent anatomical histopathology evaluation under light microscope to determine the direction of the perforation. Immunohistochemical examination was performed to determine the odontoblast like cells that express OPN and RUNX2. The results were a significant increase in the expression of OPN and RUNX2 in the combination of calcium hydroxide with chitosan compared to the control group in osteoporosis. The conclusion is in osteoporosis, the expression of OPN and RUNX2 in the combination of calcium hydroxide with chitosan on day 1, day 3 and day 6 was higher than calcium hydroxide. [ABSTRACT FROM AUTHOR]

Introduction: Anadara granosa (blood clam) shell contained 98.7% of calcium carbonate (CaCO3). This material has bio-properties that able to induced the dentin regeneration. This study is expected to reveal the nuclear factor kappa beta (NF-kB), transforming growth factor beta (TGF-β1), and vascular endothelial growth factor A (VEGF-A) expression in dental pulp after application of CaCO3 from Anadara granosa shell Material and methods: The thirty Rattus norvegicus strain Wistar used as model. The maxillary first molar was preparation using 0.84 mm low-speed diamond bur to made cavity. The cavity then applied glass ionomer cement (as control group) and other group applied CaCO3 from Anadara granosa shell. The teeth in each group were extracted after 1st, 3rd and 7th days of application for immunohistochemistry analysis for NF-kB, TGF-β1, and VEGF-A expression. Result: The NF-kB expression in the group with CaCO3 from Anadara granosa shell lower than control after 1st, 3rd and 7th days (p

Background: Dexamethasone (DEX) exerts anti-inflammatory and osteogenic effects. Hydroxyapatite is commonly used in bone repair due to its osteoconductivity, osseointegration, and osteogenesis induction. Hollow hydroxyapatite (HHAM) is often used as a drug carrier. Objective: This study aimed to investigate the histological responses of exposed dental pulp when dexamethasone-loaded nanohydroxyapatite microspheres (DHHAM) were used as a direct capping agent. Methods: Cavities were created in the left maxillary first molar of Wistar rats and filled with Dycal, HHAM, and DHHAM. No drug was administered to the control group. The rats were sacrificed at 1, 2, and 4 weeks after the procedure. The molars were extracted for fixation, demineralization, dehydration, embedding, and sectioning. H&E staining was performed to detect the formation of reparative dentin. H&E and CD45 immunohistochemical staining were performed to detect pulp inflammation. Immunohistochemical staining was performed to assess the expressions of dentin matrix protein 1 (DMP-1), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β. Results: The results of H&E and CD45 immunohistochemical staining showed that the degree of inflammation in the DHHAM group was less than that in the Control and HHAMgroups at 1, 2, and 4weeks after capping of the rat molar teeth (p<0.01). The H&E staining showed that the percentage of reparative dentin formed in the DHHAM group was higher than that in the Control, HHAM (p<0.001), and Dycal groups (p<0.01) at 1 and 2 weeks, and was significantly higher than that in the Control group (p<0.001) and the HHAM group (p<0.01) at 4 weeks. The immunohistochemical staining showed a lower range and intensity of expression of IL-1β, IL-6, and TNF-α and high expression levels of DMP-1 in the DHHAMgroup at 1, 2, and 4 weeks after pulp capping relative to the Control group. Conclusions: DHHAM significantly inhibited the progression of inflammation and promoted reparative dentin formation. [ABSTRACT FROM AUTHOR]

To improve the cytocompatibility of mineral trioxide aggregate (MTA) cement and its ability for reparative dentin formation, the effect of adding choline dihydrogen phosphate (CDHP), which is reported to be biocompatible, to MTA cement was investigated. The L929 cell proliferation showed that the addition of CDHP improved cell viability. The addition of CDHP shortened the setting time of MTA cement, with a significant decrease in consistency above 0.4 g/mL. Diametral tensile strength of the set cement was improved by the addition of 0.4 g/mL CDHP. Solubility was judged to be within the range of clinical application. The spontaneous precipitation of low crystalline hydroxyapatite was examined by immersing the set cement in phosphate buffer saline, and it was found that the ability of the cement with 0.4 g/mL of CDHP was significantly improved compared with that of the cement without CDHP. [ABSTRACT FROM AUTHOR]

Background: There is still a lack of knowledge regarding the permeability and configuration of infected root dentin. The aim of this ex vivo study was to compare the dentin penetrability of healthy teeth and necrotic teeth with apical periodontitis by evaluating the penetration of sodium hypochlorite (NaOCl) and to analyze the histopathological features of root dentin. Methods: Forty-eight molars were collected and divided into two groups. The clinical diagnosis for one group was pulp necrosis with apical periodontitis and the pulp and periapex were normal in the other group. Forty-eight straight roots were divided into two groups: infected and healthy. First, all root canals were stained with 2% methylene blue to visualize penetration after standard root canal instrumentation and irrigation. Transverse sections were obtained, and the dye penetration parameters were measured. The cross sections were processed to 20–30 μm and stained with hematoxylin and eosin for observation of the histopathological changes in the root dentin. Results: The maximum penetration depth, median penetration depth and penetration percentage of NaOCl solutions, in infected root canals were significantly lower than those in healthy root canals. The histopathological analysis showed that the frequency of reparative dentin formation in infected root canals was significantly greater than that in healthy root canals. Conclusions: The dentin penetrability of teeth with necrotic teeth and apical periodontitis was more superficial during root canal irrigation than that of healthy teeth. The histopathological changes in infected radicular dentin, namely the formation of reparative dentin, might be associated with the lower permeability of dentin tubules in human teeth with apical periodontitis. [ABSTRACT FROM AUTHOR]

Reparative dentin formed by dental cavity preparation (DCP) is frequently used in clinical operations and plays a pivotal role in pulp protection. Recent reports have shown that senescent cells induced by various stressors aggravate many diseases. They can be treated using senolytics, which are drugs that selectively eliminate senescent cells. However, the association between DCP, senescent cells, and senolytics remains unclear. In this study, we established a rat model of DCP and analyzed the spatiotemporal localization of senescent cells in the pulp. The results showed that p21- and p16-positive senescent cells appeared mostly around the pulp horn (PH) under DCP. Furthermore, administration of senolytics (dasatinib and quercetin) successfully eliminated these senescent cells, thereby restoring the volume of reparative dentin formation. These data indicate that senescent cells induced by DCP may hamper the formation of reparative dentin. Senescent cells may be targets for the development of new restorative dentistry therapies. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the biocompatibility of the regeneration of the dentin–pulp complex in a murine model with different treatments with MTA Angelus, NeoMTA, and TheraCal PT. An in vivo controlled experimental study of 15 male Wistar rats forming three study groups, the upper and lower central incisors were selected where pulpotomies were conducted, leaving a central incisor as control at 15, 30, and 45 days. For data analysis, these were expressed as mean ± standard deviation and were examined by Kruskal–Wallis test. Three factors were analyzed as follows: "inflammatory infiltrate; disorganization of pulp tissue, and the formation of reparative dentin". No statistical significance was found between the different groups (p > 0.05). Treatment with these three biomaterials (MTA, TheraCal PT, and Neo MTA) presented an inflammatory infiltrate and slight disorganization of the odontoblast layer in the pulp tissue of a murine model, with normal coronary pulp tissue and the formation of reparative dentin in the three experimental groups. Thus, we are able to conclude that all three are biocompatible materials. [ABSTRACT FROM AUTHOR]

Substance P (SP) is a neuropeptide released from the nervous fibers in response to injury. In addition to its association with pain and reactions to anxiety and stress, SP exerts various physiological functions by binding to the neurokinin-1 receptor (NK1R). However, the expression and role of SP in reparative dentinogenesis remain elusive. Here, we explored whether SP is involved in odontoblastic differentiation during reparative dentinogenesis. Dental pulp stem cells (DPSCs) were isolated from healthy human dental pulp tissues and subjected to odontoblastic differentiation. The expression of SP and NK1R during odontoblastic differentiation was investigated in vitro. The effects of SP on odontoblastic differentiation of DPSCs were evaluated using alizarin red staining, alkaline phosphatase staining, and real-time polymerase chain reaction. After direct pulp capping with mineral trioxide aggregate, the expression of SP and NK1R during reparative dentin formation in rats were identified using histological and immunohistochemical staining. SP and NK1R expression increased during the odontoblastic differentiation of DPSCs. SP translocated to the nucleus when DPSCs were exposed to differentiation medium. NK1R was always present in the nuclei of DPSCs and odontoblast-like cells. Additionally, we discovered that 10−8 M SP marginally enhanced the odontoblastic differentiation of DPSCs, and that these effects could be impaired by the NK1R antagonist. Furthermore, SP and NK1R were expressed in odontoblast-like and dental pulp cells during reparative dentin formation in vivo. SP contributes to odontoblastic differentiation during reparative dentin formation by binding to the NK1R. [ABSTRACT FROM AUTHOR]

Anadara granosa (blood clam) shell contained 98.7% of calcium carbonate (CaCO 3). This material has bio-properties that able to induced the dentin regeneration. This study is expected to reveal the nuclear factor kappa beta (NF-kB), transforming growth factor beta (TGF-β1), and vascular endothelial growth factor A (VEGF-A) expression in dental pulp after application of CaCO 3 from Anadara granosa shell The thirty Rattus norvegicus strain Wistar used as model. The maxillary first molar was preparation using 0.84 mm low-speed diamond bur to made cavity. The cavity then applied glass ionomer cement (as control group) and other group applied CaCO 3 from Anadara granosa shell. The teeth in each group were extracted after 1st, 3rd and 7th days of application for immunohistochemistry analysis for NF-kB, TGF-β1, and VEGF-A expression. The NF-kB expression in the group with CaCO 3 from Anadara granosa shell lower than control after 1st, 3rd and 7th days (p < 0.05). In other hand, the TGF-β1 and VEGF-A expression in the group with CaCO 3 from Anadara granosa shell higher than control after 1st, 3rd and 7th days (p < 0.05). CaCO 3 from Anadara granosa shell able to stimulate the TGF-β1 and VEGF-A and suppress the NF-kB expression in the dental pulp. This material able to develop as dentin-pulp material restoration. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: As an effort to treat a deep caries lesion with a diagnosis of reversible pulpitis, one of the treatment options is pulp capping. For decades, calcium hydroxide has been considered the most acceptable pulp capping material and has been routinely used in dental practice, but it also has some weakness. To overcome that, alternative materials are needed that can provide a better effect. Recently, a lot of research has been done using natural ingredients, including Propolis. Propolis has been known to have strong antimicrobial and anti-inflammatory properties. Therefore, it is necessary to conduct a deeper study regarding the potency of propolis extract as an anti-inflammatory agent for the stimulation of reparative dentin formation so that it can be considered to be used as a pulp capping material. Purpose: The aim of this literature review is to highlight the potency of propolis extract as anti-inflammatory agent in the natural stimulation of reparative dentin formation. Methods: The search strategy consist of electronic research using databases such as PubMed, Google Scholar, Science Direct, dan Springer Link for studies published from 2003 to 2021 regarding the potency of propolis extract as anti-inflammatory agent for stimulation of reparative dentin formation, including review articles and research articles. Results: Propolis and its constituents have been proven to be used as a potent natural anti-inflammatory, it also considered to have the ability to promote reparative dentin formation. However, there are some literatures stated that reparative dentin does not form with the application of propolis, and the causes may vary. Conclusion: Propolis extract has a potency as an anti-inflammatory agent in dental pulp inflammation by inhibiting TNFα expression, and increasing TGF-β1 expression, as well as its potency in stimulating the formation of reparative dentin. Based on this review, further studies are needed. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of osteopontin (OPN) on cultured human dental pulp cells (hDPCs) in relation to adhesion, proliferation, differentiation, and mineralization., Methodology: Subcultured hDPCs isolated from healthy human wisdom teeth were inoculated on noncoated (NC, control) and OPN-coated nontissue culture-treated polystyrene plates (Non-TCPS). Cell adhesion and proliferation were analyzed by crystal violet staining and the CCK-8 assay, respectively. Expressions of cell adhesion-related protein markers such as FAK and Akt were visualized by the Western blot. Expressions of tooth-related mRNA markers were evaluated by qRT-PCR. The localization of the OPN protein in reparative dentine formation was visualized using immunofluorescence staining. Data were analyzed using the Tukey's multiple comparison test., Results: Cell adhesion was significantly higher in OPN 1 μg/mL-coated group of the OPN, which is also comparable to that of the positive control (COL-1 group). Cell proliferation data showed a similar tendency. pFAK was activated as early as 3 h after cell inoculation in the 1 μg/mL-coated group of the OPN and COL-1 group. Moreover, the OPN stimulated hDPC mineralization in a time- and dose-dependent manner. Regarding the qPCR results, it was shown that OPN stimulated DMP-1 and DSPP expression on days 10 and 14. The RNA sequencing data implicated that the OPN promoted the gene expression of HLA-DRA, CD74, ENSG00000283390, MRPL53, NOP2, and KRTAP1-3. Finally, pulp exposure wound healing in SD rats showed that OPN expression was primarily localized in the forming reparative dentine instead of formed reparative dentine., Conclusion: Coated OPN promoted hDPC adhesion, proliferation, differentiation, and mineralization.

Although silicon is a widespread constituent in dental materials, its possible influence on the formation and repair of teeth remains largely unexplored. Here, we studied the effect of two silicic acid-releasing nanomaterials, silica and bioglass, on a living model of pulp consisting of dental pulp stem cells seeded in dense type I collagen hydrogels. Silica nanoparticles and released silicic acid had little effect on cell viability and mineralization efficiency but impacted metabolic activity, delayed matrix remodeling, and led to heterogeneous cell distribution. Bioglass improved cell metabolic activity and led to a homogeneous dispersion of cells and mineral deposits within the hydrogel. These results suggest that the presence of calcium ions in bioglass is not only favorable to cell proliferation but can also counterbalance the negative effects of silicon. Both chemical and biological processes should therefore be considered when investigating the effects of silicon-containing materials on dental tissues.

Aim: Pachymic acid (PA) has been shown to induce reparative dentinogenesis at the cellular level. The aim of the present study was to histologically evaluate reparative dentin (RD) formation by Biodentine (BIO) and PA when used as pulp capping agents in entire human tooth culture models under in vitro conditions. Materials and Methods: Forty human maxillary and mandibular premolar or third molar teeth with immature root apices were included in the study. The specimens were randomly allocated to two groups (n = 20) based on the pulp capping material used. In a tooth culture model set up, pulp (approximately 1 mm2) was intentionally exposed and capped respectively with BIO (Group I) or PA (Group II). The capping material was overlaid with a 2 mm thick layer of light cure glass ionomer cement, followed by resin composite restoration. The samples were cultured in a 5% CO2 incubator at 37°C for 45 days, with the culture media being replenished every day. At the end of the incubation period, the samples from both the groups were removed from the model and taken up for histological analysis. Results: PA formed significantly less uniform and less thicker dentin bridge compared to BIO. A mild inflammatory response was seen in PA treated samples. A more uniform odontoblast layer was seen in samples treated with BIO. Conclusion: Though PA has the potential to initiate RD formation, BIO proved to be a superior pulp capping material.

Conventional direct pulp capping, such as calcium hydroxide (Ca(OH)2) or silicate products, usually induces an inflammatory reaction to provoke pulp regeneration. Phosphophoryn (PP) and dentin sialoprotein (DSP), the two most abundant non-collagenous proteins in the dentin matrix, are responsible for dentin mineralization, pulp cell migration, and differentiation. Here we examined the PP and combined DSP/PP as bio-inductive pulp capping materials by in vitro and in vivo tests. Firstly, the effects of the PP dose on pulp cell migration and matrix protein expression were examined by an agarose bead test. Secondly, the role of recombinant DSP (recDSP) and recDSP/PP on stimulating DSP-PP transcript expression was examined by RT-PCR. DSPP mRNA was also knocked down by RNA interference (RNAi) to examine their functions on dentin matrix mineralization. Finally, we used ferret animal models to test PP and recDSP/PP acting as capping agents on in vivo pulp responses and reparative dentin formation. The result showed that intermediate-dose PP was the most effective to enhance cell migration and differentiation. RecDSP/PP strongly enhanced the DSP-PP transcript expression, while inhibition of DSPP mRNA expression by siRNAs partially or completely affected dental pulp cell mineralization. The in vivo results showed that intermediate-dose PP and recDSP/PP proteins induced less pulp inflammation and promoted reparative dentin formation. Contrarily, conventional calcium hydroxide induced severe pulp inflammation. With these findings, DSP and PP could serve as capping agents for pulp capping therapy. [ABSTRACT FROM AUTHOR]

Resin monomers and polymerisation initiators have been shown to be cytotoxic for pulp cells and to disturb odontoblast differentiation. This study aimed to compare the effect of a resin‐modified calcium silicate cement (TheraCal LC; TC) and a resin‐free calcium silicate cement (ProRoot MTA; PR) on pulpal healing after pulpotomy. Pulpotomy was performed on the maxillary first molars of 8‐week‐old rats using either PR or TC. After 1, 3, 7, 14 and 28 days, pulpal responses were assessed by micro‐computed tomography, haematoxylin–eosin staining and immunostaining against CD68, which is a pan‐macrophage marker. The results showed that pulpotomy with TC induced persistent infiltration of inflammatory cells, including CD68‐positive macrophages, and delayed the formation of reparative dentin as compared with that with PR, although both materials allowed pulpal healing over the long term. Therefore, resin‐modified TC was not as biocompatible nor bioinductive as resin‐free PR when applied on the healthy pulp of rat molars. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study is to compare the dentin bridge thickness achieved using calcium hydroxide and MTA using radiographs. METHODOLOGY: Single blinded randomized controlled trial conducted in the Operative Dentistry department at Fatima Jinnah Dental College and Hospital, Karachi. A total of 100 premolar and molar teeth with class I and II cavities were included in this study. The study participants were assigned into two groups, A and B of 50 participants each. Under local anesthesia, Group A was indirectly pulp capped with Calcium hydroxide (Dycal) and Group B received Mineral Trioxide Aggregate as an indirect pulp capping material. Both groups were then restored with Glass Ionomer Cement. Radiographic follow up was carried out at three and six months to determine mean dentin thickness of reparative dentin bridge. RESULTS: Statistical analysis was performed using SPSS v 23. Independent Sample t-test was applied to evaluate the formation of dentin bridge formation using Ca(OH)2 and MTA at 3 months & 6 months, the outcomes were highly significant (p-value<0.001). Paired sample t-test was applied to evaluate the difference in dentin bridge formation at three months and 6 months, the results were highly significant (p-value <0.001). CONCLUSION: Statistically significant difference was observed in the dentin thickness of reparative dentin bridge amongst the two groups after three months and six months. A greater success rate was noted in the MTA group as compared to the Ca(OH)2 group after 6 months. [ABSTRACT FROM AUTHOR]

The long-term use of calcium hydroxide and the recent increase in the use of hydraulic calcium-silicate cements as direct pulp-capping materials provide important clues in terms of how reparative dentin may be induced to form a "biological seal" to protect the underlying pulp tissues. In this review article, we discuss clinical and molecular perspectives of reparative dentin formation based on evidence learned from the use of these pulp-capping materials. We also discuss the emerging role of calcium as an odontoinductive component in these pulp-capping materials.

Dental pulp is a vital organ of a tooth fully protected by enamel and dentin. When the pulp is exposed due to cariogenic or iatrogenic injuries, it is often capped with biocompatible materials in order to expedite pulpal wound healing. The ultimate goal is to regenerate reparative dentin, a physical barrier that functions as a "biological seal" and protects the underlying pulp tissue. Although this direct pulp-capping procedure has long been used in dentistry, the underlying molecular mechanism of pulpal wound healing and reparative dentin formation is still poorly understood. To induce reparative dentin, pulp capping has been performed experimentally in large animals, but less so in mice, presumably due to their small sizes and the ensuing technical difficulties. Here, we present a detailed, step-by-step method of performing a pulp-capping procedure in mice, including the preparation of a Class-I-like cavity, the placement of pulp-capping materials, and the restoration procedure using dental composite. Our pulp-capping mouse model will be instrumental in investigating the fundamental molecular mechanisms of pulpal wound healing in the context of reparative dentin in vivo by enabling the use of transgenic or knockout mice that are widely available in the research community.

In the case of pulp injury, odontoblastic differentiation of dental pulp cells (DPCs) at the site of the exposed pulp is necessary for a successful direct pulp capping treatment. Calcium phosphate cement (CPC), a kind of hydroxyapatite-like bone cement, exhibits therapeutic potential in osteogenesis by regulating cell cycle progression and promoting osteoblastic differentiation. Based on the similar biological process of osteo/odontoblastic differentiation, the present study evaluated the effects of CPC on odontoblastic differentiation of DPCs in vitro and in vivo, respectively. The morphology of CPC was observed by scanning electron microscopy. Colony-forming units were used to assess the antibacterial activity. The effects of CPC on cell proliferation and odontoblastic differentiation of human dental pulp cells (hDPCs) were also measured. Histological staining was performed to observe the reparative dentin formation in rat molars. In vitro, results of antibacterial studies showed that CPC significantly inhibited the growth of Streptococcus mutans. The appropriate concentration of CPC extract showed low cytotoxicity on hDPCs. Furthermore, CPC extract also promoted odontoblastic differentiation and mineralization compared with the control group, as shown by a dynamic increase in the expression of odontogenic marker genes and the increased number of mineralized nodules at 21 days. The pulpotomy models with CPC facilitated the formation of dentin bridge with the highly expressed dentin matrix protein 1 (DMP1) in odontoblast-like cells. In conclusion, the favorable biocompatibility, antibacterial property and bio-inductivity of CPC suggest that CPC can be used as a promising direct pulp capping material. [ABSTRACT FROM AUTHOR]

The aim of the research was to examine the effect of «Trioxident», «Pulpotec» and «ViscoStat» on the pulp and periodontal tissue of white molars after the vital pulpotomy. All the rats were divided into three groups. «Trioxident» was used in the first group which consisted of 22 experimental animals, «Pulpotec» was used in the second group which consisted of 17 rats and «ViscoStat» was used in the third group which consisted of 18 experimental animals. After experimentally induced pulpitis and pulpotomy one of the studied drugs was imposed. Histological examination of the material was fulfilled in 2 weeks. The area of the reparative dentin was 296,9 mkm2 in group with «Trioxident», 335,0 mkm2 in group with «Pulpotec» and 355,1 mkm2 in group with «ViscoStat». The morphological signs of inflammation of the root pulp were absent in group with «Trioxident». The morphological signs of inflammation of the root pulp in group with «Pulpotec» and «ViscoStat» were determined in 8.3 % and in 71.4 % respectively. The experimental results confirmed that «Trioxident» provides regenerative effect on the pulp. That allows to recommend it to a wider usage in pediatric dentistry for vital pulpotomy.

The aim of this study was to evaluate the biocompatibility of the regeneration of the dentin–pulp complex in a murine model with different treatments with MTA Angelus, NeoMTA, and TheraCal PT. An in vivo controlled experimental study of 15 male Wistar rats forming three study groups, the upper and lower central incisors were selected where pulpotomies were conducted, leaving a central incisor as control at 15, 30, and 45 days. For data analysis, these were expressed as mean ± standard deviation and were examined by Kruskal–Wallis test. Three factors were analyzed as follows: “inflammatory infiltrate; disorganization of pulp tissue, and the formation of reparative dentin”. No statistical significance was found between the different groups (p > 0.05). Treatment with these three biomaterials (MTA, TheraCal PT, and Neo MTA) presented an inflammatory infiltrate and slight disorganization of the odontoblast layer in the pulp tissue of a murine model, with normal coronary pulp tissue and the formation of reparative dentin in the three experimental groups. Thus, we are able to conclude that all three are biocompatible materials.

Objectives: This study aimed to comparatively assess the histological response of the pulp toward alendronate and Biodentine in a direct pulp capping procedure., Materials and Methods: Twenty-four anterior teeth from 6 New Zealand rabbits were used in this study. Firstly, all rabbits were anesthetized according to their weight. Class V cavities were prepared on the buccal surfaces of anterior teeth. A pin-point exposure of the pulp was then made using a small, sterile round carbide bur and bleeding was arrested with a saline-soaked, sterile cotton pellet. The teeth under study were divided into 2 groups ( n = 12). The intentionally exposed pulp was capped with alendronate (Group 1) and Biodentine (Group 2), correspondingly. After 30 days, all rabbits were euthanized; the teeth under study were extracted and taken up for histological analysis., Results: Biodentine showed an intact, very dense dentin bridge formation with a uniform odontoblast (OD) layer pattern and mild or absent inflammatory response whereas specimens capped with alendronate demonstrated a dense dentin bridge formation with non-uniform OD layer pattern and mild to moderate inflammatory response., Conclusions: Biodentine showed more biocompatibility than alendronate. However, alendronate can initiate reparative dentin formation and may be used as an alternative pulp capping agent., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. The Korean Academy of Conservative Dentistry.)

Background: Minimally invasive techniques should be employed to maintain pulp vitality without affecting physiological tooth resorption for pediatric patients. This study aims to evaluate clinical and radiographic success of light cure calcium silicate and resin-modified glass ionomer (RMGI) as indirect pulp-capping agent in primary molars in children between 5 and 9 years. Materials and Methods: In this randomized clinical trial study, 40 primary molars with the International Caries Detection and Assessment System criteria 4–6 score were divided randomly into two groups after computerized randomization method. After caries excavation by minimally invasive dentistry principle, affected dentin was lined by either light cure calcium silicate (Group I) or RMGI (Group II) liner followed by composite restoration. Clinical success was determined with the absence of symptoms and bitewing radiographs were taken at baseline, 3, and 6 months' interval to measure increase in dentin increment using ImageJ software. Statistical analysis for intergroup comparison was done using Paired t-test, and Independent t-test was used for intragroup comparison. The level of statistical significance was set at P < 0.05. Results: Change in dentin increment seen from baseline to 6 months in Group I was 0.19 mm and in Group II was 0.20 mm (P = 0.924). Intragroup increment was statistically significant during all follow-up intervals for both the groups (Group I – P ≤ 0.001, Group II – P = 0.009). For baseline remaining dentin thickness >1.5 mm, statistically significant increase was observed in the dentin increment at 3 months' interval between both the groups. Conclusion: Both TheraCal LC and Vitrebond show acceptable clinical and radiographic results when used in primary molars as indirect pulp treatment agents. Both the liners are equivalent to each other in terms of feasibility and cost-effectiveness but TheraCal LC can be preferred due to better handling and avoiding the manipulation step thereby reducing treatment time.

Anchovy (Stolephorus sp) is a fish that usually consumed by most people in Indonesia. It is served as a famous dish in Indonesian cuisine. It is a natural source of calcium, phosphor, and fluoride. In dentistry, anchovy had been studied due to its bioactive content as bone stimulator and teeth development agent, topical fluoridative agent, and pulp capping agent. There are several methods in preparing anchovy extract that leads to different bioactive content. These variations provide several roles as biomaterial in dentistry. The latest issue regarding anchovy was its hydroxyapatite content. The previous study showed promising result and become a base of future exploration to obtain safe and effective treatment in dentistry. [ABSTRACT FROM AUTHOR]

Tusk fracture in elephants is a common incident often resulting in pulp exposure and pulpitis. Extensive lavage, endodontic therapy, direct pulp capping, or extraction are treatment options. In this report, the successful management of a broken tusk of a juvenile male Asian elephant (Elephas maximus) including morphological analysis of the tusk tip 2 years after surgery are presented. Treatment was carried out under barn conditions and included antimicrobial photodynamic therapy and partial pulpotomy with direct pulp capping. Immediate pain relief was reached. The fractured tusk was preserved and continued to grow. The therapeutic filling material remained intact for over 1 year but was absent 2 years after treatment. The former pulp cavity of the tusk tip was filled with reparative dentin, osteodentin, and bone, but the seal between these hard tissues and pulp chamber dentin was incomplete. Radiographs obtained 3 years after treatment showed no differences in pulp shape, pulp width, and secondary dentin formation between the treated right and the healthy left tusk. It can be concluded that in case of an emergency, the endodontic therapy of a broken elephant tusk can be attempted under improvised conditions with adequate success. Photodynamic therapy might contribute to prevent infection and inflammation of the pulp. The decision tree published by Steenkamp (2019) provides a valuable tool to make quick decisions regarding a suitable therapy of broken tusks. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to compare the effects of the collagen-BioAggregate mixture (CBA-M) and collagen-BioAggregate composite (CBA-C) sponge as a scaffolding material on the reparative dentin formation. Materials and Methods CBA-C sponge (10:1 w/w) was obtained and characterized by Scanning Electron Microscopy (SEM) and Mercury Porosimetry. Cytotoxicity of the CBA-C sponge was tested by using the L929 mouse fibroblast cell line. Dental pulp stem cells (DPSCs) were isolated from the pulp tissue of sheep teeth and characterized by flow cytometry for the presence of mesenchymal stem cell marker, CD44. The osteogenic differentiation capability of isolated DPSCs was studied by Alizarin Red staining. The cells were then used to study for the compatibility of CBA-C sponge with cell proliferation and calcium phosphate deposition. The effect of CBA-C sponge and CBA-M on the induction of dentin regeneration was studied in the perforated teeth of sheep for the eight-week period. All the analyses were performed with appropriate statistical hypothesis tests. Results CBA-C sponge was found to be biocompatible for DPSCs. The DPSCs seeded on the CBA-C sponge were able to differentiate into the osteoblastic lineage and deposit calcium phosphate crystals in vitro. Reparative dentin formation was observed after the second week in the CBA-C sponge applied group. At the end of eight weeks, a complete reparative dentin structure was formed in the CBA-C sponge applied group, whereas necrotic tissue residues were observed in groups treated with the CBA-M. Conclusion CBA-C sponge represents a better microenvironment for reparative dentin formation probably due to maintaining DPSCs and allowing their osteogenic differentiation and thus calcium phosphate deposition. [ABSTRACT FROM AUTHOR]

Pulp-capping materials are commonly adopted in the clinic to form reparative dentin and thus protect dental pulp tissues from cases of deep caries, accidentally exposed pulps or partial pulpotomy. Some traditional pulp capping materials used in the clinic include calcium hydroxide and mineral trioxide aggregates. However, there are limitations to thin restorative dentin, and a long period of time is needed to cause degenerative changes in dental pulp. In this paper, injectable colloidal gels were developed to induce the formation of reparative dentin through a simple UV method from methacrylic acid functionalized gelatin loaded with notoginsenoside R1 (Gel-MA/NGR1). The results of the physicochemical property examinations showed that the prepared Gel-MA/NGR1 hydrogel possessed an appropriate interconnected porous microarchitecture with a pore size of 10.5 micrometres and suitable mechanical properties with a modulus of 50-60 kPa, enabling cell adhesion and proliferation. The hydrogel remained hydrophilic with sustained drug release performance. In addition, Gel-MA/NGR1 significantly enhanced the odontogenetic differentiation of mouse dental papilla cells by elevating the expression levels of the dentinogenic markers ALP and OCN and extracellular matrix mineralization. In vivo stimulation was carried out by injecting the precursors into the predrilled alveolar cavity of Sprague-Dawley rats followed by immediate in situ UV crosslinking. The results showed that Gel-MA/NGR1 has a strong capacity to promote reparative dentin formation. Haematoxylin& eosin, Masson, and immunohistochemical staining (DMP-1, DSPP, OCN and RUNX2) and micro-CT were employed to illustrate the effectiveness of dentinogenesis, and the relative volumes of calcification were found to have increased ~175-fold. All of the results showed that the Gel-MA/NGR1 hydrogel promoted reparative dentin formation, which suggests that this hydrogel provides great potential as a pulp-capping material to induce dentin formation. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Aim: To evaluate the capability of Biodentine for direct pulp capping in permanent teeth. Materials and Methods: The pulp of 11 human intact premolars were mechanically exposed in standard cavity dimensions and then capped with Biodentine for direct pulp capping. After 9–12 weeks, all teeth were extracted. All teeth were scanned using intraoral radiograph or cone-beam computed tomography (CBCT) scan before, right after pulp capping therapy, and after 9–12 weeks on both patient real and extracted teeth for evaluation of reparative dentin bridge formation. All clinical symptoms and signs were also recorded. Data were collected and analyzed using the MedCal statistical software at the significance of 0.05. Results: There was reparative dentin bridge formation in all experimental teeth, on both patient real and extracted teeth. Conclusions: The Biodentine could induce the formation of reparative dentin in direct pulp capping. The CBCT scan was the reliable modality for evaluation of dentin bridge formation. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this randomized clinical trial was to evaluate efficiency of diode 808-nm (Picasso-AMD, USA) laser using power 1.5 W, continuous wave (CW), fiber diameter of 400 μm, non-initiated and in contact mode, tip angle set at 90°, beam divergence 16°, 2 s per an area with 1-mm diameter, power density 190.98 W/cm2, energy density 381.97 J/cm2, vertical and horizontal scanning movement on the exposure site, and laser irradiation combined with a resin-based tricalcium silicate material (TheraCal LC, Bisco, USA) in direct pulp capping in caries exposures of permanent teeth over a period of 6 months. Material and methods: In this randomized clinical trial, a total of 20 anterior and posterior vital teeth without symptoms and radiographic changes of 14 patients between the age group of 15–35 years, of which randomly 10 teeth were considered, each for TheraCal LC, the exposed area was sealed with TheraCal paste and TheraCal combined with diode laser; the treated area was sealed with TheraCal paste after diode 808-nm laser irradiation. At the 1-, 3-, and 6-month recall examinations, the loss of vitality, spontaneous pain, reactions to thermal stimuli and percussion, and radiographic changes were considered failure. The samples were randomly divided using runs test. Measurements on the digitized radiograph were performed at the recalls. The data were analyzed by repeated measurements ANOVA using SPSS 25. Results: Analysis had indicated that at the end of follow-ups, a statistically significant increase in dentin thickness with both groups (p value < 0.001) was found. Clinically, diode laser group has shown better results (p value < 0.001); however, radiographically, no significant difference was observed between groups (p value = 0.56). In both groups, the highest thickness of dentin formed was at the first month; 0.40 mm ± 0.19 mm (p value < 0.001). Conclusion: Diode laser 808 nm under proper parameters combined with TheraCal LC can be recommended for direct pulp therapy in caries exposure of permanent teeth. Clinical trial registration: This research was approved by Esfahan Medical University, Dental School, Azad Branch (KHUISF)) Esfahan, Iran [IR.IAU.KHUISF.REC.1397.261]. [ABSTRACT FROM AUTHOR]

Aim: The study carried objective to compare and evaluate the efficiency of Ca(OH)2, MTA on pulp repair. Materials and method: 20 Dental patients between age group of 18yrs-26yrs which were scheduled for premolars extraction for orthodontic explanation were selected. After Local anesthesia and complete isolation with elastic dam. Preparation of the ideal class I cavity by using sterile straight carbide bur (0.8mm) was done. an exposure of approximately 1.2 mm in diameter was done at center of the pulpal floor with round carbide bur of diameter of 1.2 mm was done Group I Exposed pulp of the teeth was capped with 2 mm of thick layer Ca(OH)2, Group II Exposed pulp of the teeth was capped with 2 mm thick layer of WMTA. After 30 seconds Glass ionomer (GC Fuji II, Japan) restoration was done. Atraumatic extraction was conducted after 8 weeks. Specimens were prepared for histological analysis and evaluated beneath light microscope at 4x and 400x magnification for inflammatory cell response, Tissue disorganization, Hard tissue formation. Descriptive statistics and inferential statistics were done using Tukey's HSD pair wise comparison test and one way ANOVA test. Results: Significance difference was seen in intensity and extensity of inflammatory cells; tissue disorganization and hard tissue formation among two groups (0.00<0.005). except for formation of dental bridge in continuity. Conclusion: Mineral Trioxide Aggregate is appropriate, biocompatible materials for pulp capping had optimum efficacy in the clinical setting but histological analysis directed favorable therapeutic effects of MTA than calcium hydroxide in teeth. [ABSTRACT FROM AUTHOR]

In addition to bone, the dentin‐pulp complex is also influenced by menopause, showing a decreased regenerative capacity. High levels of follicle‐stimulating hormone (FSH) during menopause could directly regulate bone metabolism. Here, the role of FSH in the odontogenic differentiation of the dentin‐pulp complex was investigated. Dental pulp stem cells (DPSCs) were isolated. CCK‐8 assays, cell apoptosis assays, Western blotting (WB), real‐time RT‐PCR, alkaline phosphatase activity assays, and Alizarin Red S staining were used to clarify the effects of FSH on the proliferation, apoptosis and odontogenic differentiation of the DPSCs. MAPK pathway‐related factors were explored by WB assays. FSH and its inhibitor were used in OVX rats combined with a direct pulp‐capping model. HE and immunohistochemistry were used to detect reparative dentin formation and related features. The results indicated that FSH significantly decreased the odontogenic differentiation of the DPSCs without affecting cell proliferation and apoptosis. Moreover, FSH significantly activated the JNK signalling pathway, and JNK inhibitor partly rescued the inhibitory effect of FSH on DPSC differentiation. In vivo, FSH treatment attenuated the dentin bridge formation and mineralization‐related protein expression in the OVX rats. Our findings indicated that FSH reduced the odontogenic capacity of the DPSCs and was involved in reparative dentinogenesis during menopause. [ABSTRACT FROM AUTHOR]

Introduction: Dental pulp tissue contains many undifferentiated mesenchymal cells, which have the ability to differentiate into different specialized cells. Induced pluripotent stem cells have been developed by various growth factors. The present study was designed to evaluate the effect of application of a combination BMP2/TGF β1 as capped material for traumatic pulp in osteoporotic rat. Materials and Methods: Twelfth female rats (6 normal rat and other 6 osteoporotic rat)., their maxillary anterior teeth subjected to mechanical traumatized pulptomy, the left tooth has speared without treatment, while the right tooth capped with application of 0.5 (U+03BC)l of BMP2 and 0.5 (U+03BC)l of TGF β1 .Evaluation of histological changes includes scoring of pulp inflammation and scoring of morphology and thickness of dentin bridge were estimated for all study groups. Results: Histological examination of tooth with pulptomy capped by BMP-2&TGF β1 for both normal and osteoporotic rat showed formation of reparative dentin bridge and minimal inflammatory response with a significant differences value in comparison to control. Conclusion: The study concludes that application of a combination of BMP-2&TGFβ1 enhanced tooth repair in osteoporotic rat. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the contribution of bone marrow–derived cells (BMDCs) to reparative dentinogenesis using bone marrow transplantation (BMT) and pulp capping as an in vivo model. A chimeric mouse model was created through the injection of BMDCs expressing green fluorescent protein (GFP+ BMDCs) from C57BL/6 GFP+ transgenic donor mice into irradiated C57BL/6 wild-type recipient mice (GFP− mice). These GFP− chimeric mice (containing transplanted GFP+ BMDCs) were subjected to microscopic pulp exposure and capping with white mineral trioxide aggregate (n = 18) or Biodentine (Septodont, St Maur-des-Fossés, France) (n = 18) in the maxillary first molar. Maxillary arches from GFP− chimeric mice (with the capped tooth) were isolated and histologically processed 5 (n = 9) and 7 (n = 9) weeks after BMT. Confocal laser microscopy and immunohistochemical analysis were performed to assess the presence of GFP+ BMDCs and the expression of dentin sialoprotein, an odontoblast marker, for those cells contributing to reparative dentinogenesis in the dental pulp. Confocal laser microscopic analyses evidenced the presence of GFP+ BMDCs in close association with reparative dentin synthesized at the site of pulp exposure in GFP− mice 5 and 7 weeks after BMT. Immunohistochemical analysis revealed that GFP+ BMDCs in close association with reparative dentin expressed DSP, suggesting the contribution of nonresident GFP+ BMDCs to reparative dentinogenesis. These data suggest the presence of nonresident BMDCs in reparative dentinogenesis and its contribution to dental pulp regeneration in the pulp healing process. [ABSTRACT FROM AUTHOR]

Direct pulp capping is an effective treatment for preserving dental pulp against carious or traumatic pulp exposure via the formation of protective reparative dentin by odontoblast-like cells. Reparative dentin formation can be stimulated by several signaling molecules; therefore, we investigated the effects of secreted frizzled-related protein (SFRP) 1 that was reported to be strongly expressed in odontoblasts of newborn molar tooth germs on odontoblastic differentiation and reparative dentin formation. In developing rat incisors, cells in the dental pulp, cervical loop, and inner enamel epithelium, as well as ameloblasts and preodontoblasts, weakly expressed Sfrp1; however, Sfrp1 was strongly expressed in mature odontoblasts. Human dental pulp cells (hDPCs) showed stronger expression of SFRP1 compared with periodontal ligament cells and gingival cells. SFRP1 knockdown in hDPCs abolished calcium chloride-induced mineralized nodule formation and odontoblast-related gene expression and decreased BMP-2 gene expression. Conversely, SFRP1 stimulation enhanced nodule formation and expression of BMP-2. Direct pulp capping treatment with SFRP1 induced the formation of a considerable amount of reparative dentin that has a structure similar to primary dentin. Our results indicate that SFRP1 is crucial for dentinogenesis and is important in promoting reparative dentin formation in response to injury.

This study was performed to examine whether calcium silicate could induce reparative dentin formation without eliciting any adverse effect in direct pulp capping of premolar teeth. Twenty participants who need extraction of their 4 healthy permanent premolar teeth for orthodontic reasons were included in this study. Following the surgical procedure, the exposed pulp tissue was treated either with calcium silicate or covered with calcium hydroxide paste. On day 3, 7, 14 and 28, the experimental teeth was extracted and examined using light microscopy and histometric analysis to observe the inflammatory changes and the amount of reparative dentin formation. The results showed that in the calcium silicate treated teeth, substantial amounts of dentine-like tissue was formed on day 14 and mostly located on the exposure site. It was also observed in the calcium hydroxide treated teeth but dentin-like tissue located at a distance from the exposure site. The total amount of reparative dentine formed in the calcium silicate-treated teeth was significantly higher (p

Dental pulp is a dynamic tissue able to heal after injury under moderate inflammatory conditions. Our study aimed to evaluate pulp repair under inflammatory conditions in rats. For this purpose, we developed a rat model of controlled pulpitis followed by pulpotomy with a tricalcium silicate-based cement. Fifty-four cavities were prepared on the occlusal face of the maxillary upper first molar of 27 eight-week-old male rats. E. coli lipopolysaccharides at 10 mg/mL or phosphate-buffered saline PBS was injected after pulp injury. Non-inflamed molars were used as controls. Levels of inflammation-related molecules were measured 6 and 24 h after induction by enzyme-linked immunosorbent assay of coronal pulp samples. Pulp capping and coronal obturation after pulpotomy were performed with tricalcium silicate-based cement. Four and fifteen days after pulpotomy, histological and immunohistochemical analysis was performed to assess pulp inflammation and repair processes. Our results showed significantly higher levels of innate inflammatory proteins (IL-1β, IL-6, TNF-α and CXCL-1) compared with those in controls. Moderate residual inflammation near the capping material was demonstrated by histology and immunohistochemistry, with the presence of few CD68-positive cells. We showed that, in this model of controlled pulpitis, pulpotomy with BiodentineTM allowed the synthesis at the injury site of a mineralized bridge formed from mineralized tissue secreted by cells displaying odontoblastic characteristics. Analysis of these data suggests overall that, with the limitations inherent to findings in animal models, pulpotomy with a silicate-based cement is a good treatment for controlling inflammation and enhancing repair in cases of controlled pulpitis.

Pulp capping materials allow healing of injured pulp with a layer of reparative dentin. Glucose is needed to cure the injured area. Glucose is transported by glucose transporter (Glut) 2 and Glut4, which are transmembrane proteins that act as gatekeepers. We hypothesized that the transport of glucose via Glut2/Glut4 might contribute to the production of a dentin bridge during wound healing. Therefore, we explored Glut2 and Glut4 expression during reparative dentinogenesis after mineral trioxide aggregate capping. The upper left first molar of 8-week-old Wistar rats underwent pulpotomy with mineral trioxide aggregate. At 1, 3, 5, 7, and 14 days after treatment, localization and colocalization of Glut2, Glut4, nestin (odontoblast marker), and antiendothelial cell antigen 1 (RECA-1; endothelial cell marker) were analyzed with immunohistochemical staining. Messenger RNA expression levels of Slc2a2 (encoding Glut2), Slc2a4 (encoding Glut4), Igf-1r (encoding insulinlike growth factor 1 receptor), and nestin were analyzed in the extracted teeth using real-time polymerase chain reaction. Glut2 and Glut4 were localized within odontoblasts and endothelial cells in normal control teeth. Three days after pulpotomy, Glut2- and Glut4-positive cells were detected; 7 days after pulpotomy, immunoreactivity for Glut2 and Glut4 was confined to newly differentiated odontoblastlike cells arranged beneath reparative dentin. Messenger RNA expression levels of Slc2a2 and Slc2a4 were significantly up-regulated after pulpotomy. Glut2 and Glut4 regulate glucose transport during wound healing beneath the injured area. This may contribute to the development of new vital pulp therapy for patients with deep caries. [ABSTRACT FROM AUTHOR]

Bone sialoprotein (BSP) is a member of the SIBLING family with essential roles in skeletogenesis. In the developing teeth, although the expression and function of BSP in the formation of acellular cementum and periodontal attachment are well documented, there are uncertainties regarding the expression and function of BSP by odontoblasts and dentin. Reporter mice are valuable animal models for biological research, providing a gene expression readout that can contribute to cellular characterization within the context of a developmental process. In the present study, we examined the expression of a BSP-GFPtpz reporter mouse line during odontoblast differentiation, reparative dentinogenesis, and bone. In the developing teeth, BSP-GFPtpz was expressed at high levels in cementoblasts but not in odontoblasts or dentin. In bones, the transgene was highly expressed in osteoblasts at an early stage of differentiation. Interestingly, despite its lack of expression in odontoblasts and dental pulp during tooth development, the BSP-GFPtpz transgene was detected during in vitro mineralization of primary pulp cultures and during reparative dentinogenesis following pulp exposures. Importantly, under these experimental contexts, the expression of BSP-GFPtpz was still exclusive to DSPP-Cerulean, an odontoblast-specific reporter gene. This suggests that the combinatorial use of BSP-GFPtpz and DSPP-Cerulean can be a valuable experimental tool to distinguish osteogenic from dentinogenic cells, thereby providing an avenue to investigate mechanisms that distinctly regulate the lineage progression of progenitors into odontoblasts versus osteoblasts. [ABSTRACT FROM AUTHOR]

Aims and Objectives: The aim of this study was to compare the clinical performance of mineral trioxide aggregate (MTA) and calcium hydroxide as indirect pulp-capping agents in permanent teeth. Materials and Methods: Search strategy includes randomized control trials and clinical trials from the databases of PubMed Central, Cochrane, EBSCO, and MEDLINE from January 1998 to May 2018. A total of six clinical trials that met all inclusion criteria were included in this systematic review. Meta-analysis was performed for three among the included studies. The primary clinical outcome of the included studies was to evaluate the pulp vitality with a normal response to thermal, electrical, and tactile tests without signs of spontaneous pain. The radiological outcome was to evaluate the absence of periapical radiolucency, periodontal ligament space widening, and the dentin bridge formation. The primary and predominant results were assessed based on the success or failure of pulp capping. The restorations were considered failure when there are clinical symptoms such as pain and tenderness and radiographic evidence of radiolucency in periapical region or widening of periodontal ligament. Results: In the six trials that are included, two studies are judged as low risk and four as medium risk of bias. With the help of meta-analysis, the evidence produced concluded that after six-month and one-year follow-up there was no statistically significant difference between MTA and calcium hydroxide as an indirect pulp-capping material. Conclusion: This systematic review of the available evidence reveals that MTA and calcium hydroxide demonstrated good consistent endurance in clinical studies and indistinguishable performance. [ABSTRACT FROM AUTHOR]

Bioactivity of Bio-MA, a calcium chloride accerelator-containing calcium-silicate cement, as a pulp capping material was evaluated on mechanically exposed rat molar pulp. Sixty maxillary first molars from Wistar rats were mechanically exposed and assigned to two capping materials: Bio-MA or white mineral trioxide aggregate (WMTA), and three periods: 1, 7, or 30 days. Nine molars were exposed and covered with polytetrafluoroethylene tape, as positive controls. From histological examination, inflammatory cell infiltration and reparative dentin formation were evaluated using grading scores. No significant difference in pulpal responses between the two materials was observed at any period (p>0.05). At 1 day, all experimental groups showed localized mild inflammation. At 7 days, dentin bridge was partially observed at exposure sites with few inflammatory cells. At 30 days, pulp appeared normal with complete tubular dentin bridges. Bio-MA with accerelator was biocompatible similar to WMTA and could be used as a pulp-capping material. [ABSTRACT FROM AUTHOR]

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This study examined and compared wound healing between Thai propolis product and calcium hydroxide paste as pulp-capping agents after partial pulpotomy in New Zealand white rabbits. Forty incisor teeth from 10 rabbits were treated. Thirty-six teeth received class V cavity preparations with partial pulpotomy and application of either propolis or calcium hydroxide paste. Similar cavity preparations were performed in 2 teeth without any capping material as a positive control, whereas 2 teeth without the cavity preparation served as a negative control. Histological evaluation showed that both groups had dentin bridge formation. Dentinal tubules in the dentin bridge were more orderly arranged in the Thai propolis group than in the calcium hydroxide group. Wound healing and the median number of hyperemic blood vessels were not statistically significant different between the 2 groups. Thai propolis product may be used as a pulp-capping agent. [ABSTRACT FROM AUTHOR]