Reparative Dentin Formation Research Articles

Piezo Mediates the Mechanosensation and Injury-Repair of Pulpo-Dentinal Complex

ObjectivesThe aim of this research was to investigate the functions of Piezo channels in dentin defect, including mechanical signalling and odontoblast responses. MethodsRat dentin-defect models were constructed, and spatiotemporal expression of Piezo proteins was detected in the pulpo-dentinal complex. Real-time polymerase chain reaction (rtPCR) was used to investigate the functional expression pattern of Piezo channels in odontoblasts. Moreover, RNA interference technology was employed to uncover the underlying mechanisms of the Piezo-driven inflammatory response and repair under fluid shear stress (FSS) conditions in vitro. ResultsPiezo1 and Piezo2 were found to be widely expressed in the odontoblast layer and dental pulp in the rat dentin-defect model during the end stage of reparative dentin formation. The expression levels of the Piezo1 and Piezo2 genes in MDPC-23 cells were high in the initial stage under FSS loading and then decreased over time. Moreover, the expression trends of inflammatory, odontogenic, and mineralisation genes were generally contrary to those of Piezo1 and Piezo2 over time. After silencing of Piezo1/Piezo2, FSS stimulation resulted in significantly higher expression of inflammatory, odontogenesis, and mineralisation genes in MDPC-23 cells. Finally, the expression of genes involved in the integrin β1/ERK1 and Wnt5b/β-catenin signalling pathways was changed in response to RNA silencing of Piezo1 and Piezo2. ConclusionsPiezo1 and Piezo2 may be involved in regulating the expression of inflammatory and odontogenic genes in odontoblasts stimulated by FSS.

Combination Calcium Hydroxide and Epigallocatechin-3-gallate in Dentistry: A Narrative Review

Background: Pulp capping and pulpotomy are treatments for exposed pulp due to injury. Calcium hydroxide is the gold standard material in pulp capping and pulpotomy because it stimulates reparative dentin formation in exposed pulp. Calcium hydroxide has the disadvantage of causing chronic inflammation, cell necrosis, the formation of tunnel defects, and weak antibacterial properties against certain bacteria. Epigallocatechin-3-gallate (EGCG) is the main catechin component of green tea and has potent anti-inflammatory and antibacterial properties against both gram-negative and positive bacteria. The addition of EGCG to calcium hydroxide has the potential to prevent chronic inflammation and improve the antibacterial properties of calcium hydroxide. Purpose: This review aims to explain the potential of the combination of calcium hydroxide and EGCG in dentistry. Review(s): EGCG has potent anti-inflammatory and antibacterial effects against Enterococcus faecalis. The addition of EGCG to calcium hydroxide has the potential to reduce the inflammatory effect and improve the antibacterial properties of calcium hydroxide. Conclusion: This review concludes that the combination of calcium hydroxide and EGCG has the potential to reduce the inflammatory effect and promote the antibacterial effect of calcium hydroxide. Further research is needed to prove the potential of the combination of calcium hydroxide and EGCG in dentistry as a material for pulp capping and pulpotomy.

LAMA5-inspired adhesive dodecapeptide facilitates efficient dentine regeneration: An in vitro and in vivo study.

The primary goal of this study was to investigate the potential effects of A5G81 in inducing reparative dentine (RD) formation both in vitro and in vivo. Cell adhesion was observed by crystal violet staining and quantified by Sodium Dodecyl Sulphate (SDS) extraction. Cell proliferation was investigated using Cell Counting Kit-8 (CCK-8) assay. Spreading of cytoskeleton was visualized using immunofluorescence staining. Protein expression level of Akt signalling pathway was compared in a human Akt pathway phosphorylation array. Genes that were up or downregulated by A5G81 were identified by RNA sequencing. The mRNA expression of odontoblastic markers was detected by quantitative real-time polymerase chain reaction (qPCR). Moreover, mineralization of human dental pulp cells (hDPCs) was visualized by alizarin red staining and quantified using cetylpyridinium chloride (CPC). A direct pulp-capping model was established in SD rats and the RD formation at 2 weeks after operation was observed using HE staining. A5G81 (optimal coating concentration: 0.5 mg/mL) promoted hDPCs adhesion and proliferation to a level that was similar to Type I collagen (COL-1). Meanwhile, A5G81 activated Akt signalling pathway, albeit to a lesser extent than COL-1. An inhibition test indicated that A5G81 induced hDPCs adhesion by activating PI3K pathway. A5G81 induced the expression of ECM remodelling genes and odontoblastic genes, which were demonstrated by RNA-seq and qPCR, respectively. In addition, A5G81 efficiently accelerated the mineralization of hDPCs in both immobilized and soluble forms, a property that makes it more applicable in dental clinic. Finally, the pulp-capping study in rats suggested that use of A5G81 could successfully induce the formation of RD within 2 weeks. Coating of A5G81 to non-tissue culture-treated polystyrene facilitates spreading, proliferation and differentiation of hDPCs, resulting in rapid RD formation in artificially exposed pulp.

Experimental study of dexamethasone-loaded hollow hydroxyapatite microspheres applied to direct pulp capping of rat molars.

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. 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. 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. 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 HHAM groups at 1, 2, and 4 weeks 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 DHHAM group at 1, 2, and 4 weeks after pulp capping relative to the Control group. DHHAM significantly inhibited the progression of inflammation and promoted reparative dentin formation.

Functional evaluation of mineral trioxide aggregate cement with choline dihydrogen phosphate.

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.

Reparative Dentin Formation Following Dental Pulp Capping is Mediated by TNFR1 In Vivo

IntroductionTumor necrosis factor (TNF)-α is a pro-inflammatory cytokine that promotes biomineralization in vitro in dental pulp cells. However, the role of TNF-α-TNF receptor 1 (TNFR1) signaling in reparative dentin formation and related inflammatory pathways is not known. Therefore, the aim of this study was to evaluate the role of the TNF-α-TNFR1 axis in dental pulp repair following pulp capping in vivo. MethodsDental pulp repair response of genetically deficient TNF-α receptor-1 mice (TNFR1−/−; n = 20) was compared with that of C57Bl6 mice (wild type [WT]; n = 20). Pulp capping was performed with mineral trioxide aggregate on the mandibular first molars of mice. After 7 and 70 days, tissues were collected and stained with hematoxylin and eosin for histopathological and histometric evaluation, and assessed by the Brown and Brenn methods for histomicrobiological analysis and by immunohistochemistry to localize TNF-α, Runt-related transcription factor 2, Dentin Sialoprotein (DSP) and Osteopontin (OPN) expression. ResultsCompared with WT mice, TNFR1−/− mice showed significantly decreased reparative dentin formation with a lower mineralized tissue area (P < .0001). Unlike WT mice, TNFR1−/− mice also exhibited significant dental pulp necrosis, neutrophil recruitment, and apical periodontitis formation (P < .0001) without bacterial tissue invasion. TNFR1−/− animals further exhibited decreased TNF-α, DSP, and OPN expression (P < .0001), whereas Runt-related transcription factor 2 expression was unchanged (P > .05). ConclusionThe TNF-α-TNFR1 axis is involved in reparative dentin formation following dental pulp capping in vivo. Genetic ablation of TNFR1 modified the inflammatory process and inhibited the expression of the DSP and OPN mineralization proteins, which culminated in dental pulp necrosis and development of apical periodontitis.

Inflammatory Response and Odontogenic Differentiation of Inflamed Dental Pulp Treated with Different Pulp Capping Materials: An In Vivo Study.

Previous studies have evaluated the pulpal responses to calcium silicate cements (CSCs) on normal dental pulp, but investigations on the effects of CSCs on inflamed pulp are limited. This study aimed to test the inflammatory response and odontogenic differentiation of inflamed rat dental pulp after direct pulp capping with CSCs. Wistar rat molars pulps were exposed for 48 hours to induce inflammation and then capped with ProRoot MTA (Dentsply, Tulsa, OK, USA), Biodentine (Septodont, Saint-Maur-des-Fossés, France), RetroMTA (Bio MTA, Seoul, Korea) and Dycal (Dentsply Caulk, Milford, DE, USA). The degree of pulpal inflammation and hard tissue formation was evaluated by histological analysis. Immunofluorescence staining for interleukin (IL)-6, osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) was also performed. After 4 weeks, complete recovery from inflammation was evident in 22%, 37.5%, 10%, and none of the ProRoot MTA, Biodentine, RetroMTA and Dycal samples, respectively. Heavy hard tissue deposition as a continuous hard tissue bridge was observed in 77.8%, 75%, 70%, and 60% of the ProRoot MTA, Biodentine, RetroMTA, and Dycal samples, respectively. IL-6, OCN, and RUNX2 were detected in all materials, mainly adjacent to areas of inflammation and reparative dentine formation. At 1, 2, and 4 weeks, significant differences were not observed between the inflammation and hard tissue formation scores of the four material groups (P > .05). In this study, pulpal inflammation was still present in most specimens at 4 weeks after pulp capping and a significant number of samples showed incomplete and discontinuous dentine bridge formation. The results of this study suggest that initial inflammatory conditions of the pulp may risk the prognosis of teeth treated with CSCs.

GATA4 inhibits odontoblastic differentiation of dental pulp stem cells through targeting IGFBP3

ObjectiveThe odontogenic differentiation of human dental pulp stem cells (HDPSCs) is associated with reparative dentinogenesis. Transcription factor GATA binding protein 4 (GATA4) is proved to be essential for osteoblast differentiation and bone remodeling. This study clarified the function of GATA4 in HDPSCs odontoblast differentiation. MethodsThe change in GATA4 expression during reparative dentin formation was detected by immunohistochemistry staining. The expression of GATA4 during HDPSCs odontoblastic differentiation was detected by western blot and quantitative polymerase chain reaction. The effect of GATA4 on odontoblast differentiation was investigated following overexpression lentivirus transfection. RNA sequencing, dual luciferase assay and chromatin immunoprecipitation (CHIP) were conducted to verify downstream targets of GATA4. GATA4 overexpression lentivirus and small interference RNA targeting IGFBP3 were co-transfected to investigate the regulatory mechanism of GATA4. ResultsUpregulated GATA4 was observed during reparative dentin formation in vivo and the odontoblastic differentiation of HDPSCs in vitro. GATA4 overexpression suppressed the odontoblastic potential of HDPSCs, demonstrated by decreased alkaline phosphatase activity (p < 0.0001), mineralized nodules formation (p < 0.01), and odonto/osteogenic differentiation markers levels (p < 0.05). RNA sequencing revealed IGFBP3 was a potential target of GATA4. CHIP and dual luciferase assays identified GATA4 could activate IGFBP3 transcription. Additionally, IGFBP3 knockdown recovered the odontoblastic differentiation defect caused by GATA4 overexpression (p < 0.05). ConclusionsGATA4 inhibited odontoblastic differentiation of HDPSCs via activating the transcriptional activity of IGFBP3, identifying its promising role in regulating HDPSCs odontoblast differentiation and reparative dentinogenesis.

The potency of propolis extract as anti-inflammatory agent for stimulation of reparative dentin formation

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. Objective: 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 an 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.

Reparative dentin formation as a possible factor influencing the penetrability of dentin in human teeth with apical periodontitis: an ex vivo study

BackgroundThere 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.MethodsForty-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.ResultsThe 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.ConclusionsThe 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.

Multimodal Imaging of Dental Pulp Healing Patterns Following Tooth Autotransplantation and Regenerative Endodontic Treatment

IntroductionUnderstanding the healing process of dental pulp after tooth autotransplantation (TAT) and regenerative endodontic treatment (RET) of immature teeth is important both clinically and scientifically. This study aimed to characterize the pattern of dental pulp healing in human teeth that underwent TAT and RET using state-of-the-art imaging techniques. Materials and MethodsThis study examined 4 human teeth, 2 premolars that underwent TAT, and 2 central incisors that received RET. The premolars were extracted after 1 year (case 1) and 2 years (case 2) due to ankylosis, while the central incisors were extracted after 3 years (cases 3 and 4) for orthodontic reasons. Nanofocus x-ray computed tomography was used to image the samples before being processed for histological and immunohistochemical analysis. Laser scanning confocal second harmonic generation imaging (SHG) was used to examine the patterns of collagen deposition. A maturity-matched premolar was included as a negative control for the histological and SHG analysis. ResultsAnalysis of the 4 cases revealed different patterns of dental pulp healing. Similarities were observed in the progressive obliteration of the root canal space. However, a striking loss of typical pulpal architecture was observed in the TAT cases, while a pulp-like tissue was observed in one of the RET cases. Odontoblast-like cells were observed in cases 1 and 3. ConclusionsThis study provided insights into the patterns of dental pulp healing after TAT and RET. The SHG imaging sheds light on the patterns of collagen deposition during reparative dentin formation.

Localization of senescent cells under cavity preparations in rats and restoration of reparative dentin formation by senolytics.

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.

Potential Combination of Acemannan Sponge and Calcium Phosphate Cement-Calcium Sulfate Hemihydrate (CPC-CSH) as Direct Pulp Capping Alternative Materials for Reparative Dentin Formation

Abstract Background Health problem that affects hard tissues of the teeth is dental caries, which is experienced by around 2.3 billion people in the world, with prevalence in Indonesia reaching 88.8. Direct pulp capping (DPC) is a vital pulp therapy used to maintain pulp vitality. Calcium hydroxide (Ca(OH)2) is the gold standard pulp capping material, but has poor adhesion to dentin and mechanical properties, bacterial infiltration, formation of tunnel defects in the pulp resorption, and dentin bridge. Therefore, it is necessary to develop alternative therapy, namely, a combination of acemannan sponge and calcium phosphate cement (CPC)-calcium sulfate hemihydrate (CSH) for reparative dentin formation. Purpose This article describes the potential combination of acemannan sponge and CPC-CSH as DPC alternative materials for reparative dentin formation. Reviews Acemannan extracted from aloe vera exhibits anti-inflammatory, antimicrobial, and cytocompatibility properties. As DPC material, acemannan induces pulp proliferation and differentiation to osteoblast-like, growth factor synthesis, and promotes reparative dentin formation. However, acemannan sponge is radiolucent, allowing misinterpretation between pulp and acemannan sponge. CPC can be combined with CSH to shorten the setting time. CPC-CSH is radiopaque, has good compressive strength, and biocompatibility. CPC-CSH is a calcium-based material with neutral pH that can induce the dentin bridge formation. CPC-CSH showed good bioactivity because it induces the formation of apatite which plays a significant part in dentin and pulp regeneration. Conclusion The combination of acemannan sponge and CPC-CSH has the potential as DPC alternative materials for reparative dentin formation.

Cold lasers for photobiomodulation in pulpotomy of primary molars: A short review

Photobiomodulation with diode lasers of 660 and 810 - 980 nm is used for the proliferation of fibroblasts and to enhance the healing of oral lesions or surgical wounds. It has the potential to stimulate the formation of reparative dentin and preserve pulp vitality. Photobiomodulation uses low-level laser therapy (LLLT) which works on the principle of supplying direct bio-stimulative light energy to the cells. Based on these characteristics, numerous studies are conducted on photobiomodulation with a diode laser for pulpotomy in primary molars. This review article aims to provide data to clinicians regarding varying parameters used for photobiomodulation in pulpotomy and their clinical outcomes in primary molars.

Enhancing Effects of Immobilized Chondroitin Sulfate on Odontogenic Differentiation of Dental Pulp Stem Cells and Reparative Dentin Formation

IntroductionChondroitin sulfate (CS) is a major proteoglycan involved in the mineralization of the organic matrix of dentin. In this study, the roles of CS immobilized in cross-linked collagen I (Col I) hydrogels on odontogenic differentiation of dental pulp stem cells (DPSCs) and reparative dentin formation were investigated. MethodsDifferent concentrations of CS were incorporated into the genipin–cross-linked Col I hydrogels (CS-0.05, CS-0.1, and CS-0.2, respectively). The influences of CS on the proliferation and odontogenic differentiation of DPSCs were investigated. Finally, the effect of the functionalized hydrogel on the formation of reparative dentin was analyzed in a rat pulp capping model in vivo. ResultsCS improved the proliferation of DPSCs seeded on the hydrogels (P < .05). CS also enhanced the mineralization activities and increased the expression levels of the odontogenic-related proteins of DPSCs on days 7 and 14 (P < .05). In vivo, CS-0.1 hydrogel induced reparative dentin formation with higher quality compared with mineral trioxide aggregate. ConclusionsCS immobilized in Col I hydrogels could induce odontogenic differentiation of DPSCs in vitro and promote homogeneous mineralized barrier formation in vivo. CS–Col I hydrogel has the potential for reparative dentin formation of high quality in direct pulp capping.

Dental Pulp Response to Silver-Containing Solutions: A Scoping Review.

Dentists used silver-containing solutions for deep cavity disinfection before restoration. This review aims to identify the silver-containing solutions reported in the literature for deep cavity disinfection and summarize their effects on dental pulp. An extensive search was performed using the search words "(silver) AND (dental pulp OR pulp)" in ProQuest, PubMed, SCOPUS, and Web of Science to identify English publications on silver-containing solutions for cavity conditioning. The pulpal response to the included silver-containing solutions was summarized. The initial search identified 4112 publications and 14 publications met the inclusion criteria. Silver fluoride, silver nitrate, silver diamine nitrate, silver diamine fluoride, and nano-silver fluoride were used in deep cavities for antimicrobial purposes. Indirect silver fluoride application induced pulp inflammation and reparative dentine in most cases, and pulp necrosis in some cases. Direct silver nitrate application caused blood clots and a wide inflammatory band in the pulp, whilst indirect silver nitrate application caused hypoplasia in shallow cavities and partial pulp necrosis in deep cavities. Direct silver diamine fluoride application induced pulp necrosis, while indirect silver diamine fluoride application induced a mild inflammatory response and reparative dentine formation. No evidence of the dental pulpal response to silver diamine nitrate or nano-silver fluoride was available in the literature.

Concentrated growth factor combined with iRoot BP Plus promotes inflamed pulp repair: an in vitro and in vivo study

BackgroundPlatelet concentrates combined with calcium silicate cements may promote reparative dentin formation. However, few studies have reported their effect on dental pulp inflammation. This study aimed to evaluate the effects of concentrated growth factor (CGF) combined with iRoot BP Plus on inflammatory human dental pulp stem cells (hDPSCs) in vitro and inflamed pulp in rats in vivo.MethodsThe proliferation of LPS-stimulated hDPSCs treated with 50% CGF with/without 25% iRoot BP Plus was evaluated using Cell Counting Kit-8 on days 1, 4 and 7. The expression of genes associated with inflammation on day 1 and differentiation on day 14 was analysed by real-time polymerase chain reaction. The exposed pulp of rat maxillary molars was injected with 10 mg/mL LPS and directly capped with CGF membrane with/without iRoot BP Plus extract for 1, 7 and 28 days. The teeth were subjected to histologic analyses and immunohistochemistry.ResultsThe proliferation rates of the inflammatory hDPSCs after the combination treatment were significantly higher than those after the other treatments on days 4 and 7 (P < 0.05). IL-1β, IL-6, and TNF-α levels were increased in inflammatory hDPSCs but decreased after treatment with CGF combined with iRoot BP Plus extract, whereas IL-4 and IL-10 showed the opposite expression patterns. Expression of the odontogenesis-related genes OCN, Runx2, and ALP was dramatically enhanced by combined treatment with CGF and iRoot BP Plus extract. In rat pulp, the average inflammation scores of the CGF and CGF-iRoot BP Plus groups significantly decreased in comparison with those of the LPS group (P < 0.05), and the CGF-iRoot BP Plus group had more reparative dentin than the CGF and BP groups. Immunohistochemical staining showed fewer M1 macrophages on day 1 and more M2 macrophages on day 7 in the CGF-iRoot BP Plus group than in the other groups.ConclusionsThe combination of CGF and iRoot BP Plus showed a synergistic effect on anti-inflammatory potential and promoted greater pulp healing than CGF or iRoot BP Plus alone.

Impaired pulp healing associated with underlying disorders in the dental pulp of rats with type 2 diabetes

Background/purposeType 2 diabetes mellitus (T2DM), characterized by hyperglycemia, is a systematic disease affecting structure and healing ability in various tissues. This study aimed to investigate whether T2DM could impair the dental pulp healing and cause underlying pathological changes in the dental pulp before an injury occurred. Materials and methodsGoto-Kakizaki rats were used as T2DM model animals and performed with direct pulp capping procedures on the first maxillary molars. The molars at 1, 2, 4 weeks after operation and non-injured molars were examined using hematoxylin and eosin staining, immunohistochemical staining, immunofluorescence staining, and Masson's trichrome staining. The fresh dental pulp of maxillary incisors was collected for transmission electron microscopy and glucose content evaluation. ResultsThe T2DM rats showed deficient reparative dentin formation compared with the healthy rats. Before the occurrence of an injury, underlying pathological changes of major components in the pulp tissue were observed in T2DM rats, including vasculopathy; collagen abnormalities; decreased proliferation, decreased odontogenetic differentiation and damaged ultrastructure of dental pulp cells. High glucose content and advanced glycation end products accumulation were further found in the pulp tissue in T2DM rats. ConclusionT2DM can impede pulp healing process in rats, which is associated with underlying pathological changes in the non-injured pulp caused by the advanced glycation end products accumulation under high-glucose conditions.

Dopamine is involved in reparative dentin formation through odontoblastic differentiation of dental pulp stem cells

Conventional direct pulp-capping materials induce pulp cells to secrete various biomolecules in pulp tissues that promote reparative dentin formation through induction of odontoblastic differentiation of dental pulp stem cells (DPSCs). However, these biomolecules sometimes induce bone-like dentin with poor sealing properties. Therefore, exploration of biomolecules that allow tight sealing by tubular reparative dentin is required. We recently reported that dopamine (DA) is involved in dentinogenesis. Hence, we investigated the effect of DA on odontoblastic differentiation of DPSCs and reparative dentin formation. Both tyrosine hydroxylase (TH), a DA synthetase, and DA were expressed in odontoblast-like cells in vivo. In vitro, their expression was increased during odontoblastic differentiation of DPSCs. Furthermore, TH-overexpressing DPSCs had promoted odontoblastic differentiation and DA production. Moreover, DA stimulation promoted their differentiation and induced tubular reparative dentin. These results suggest that DA produced by TH is involved in odontoblastic differentiation of DPSCs and has an inductive capacity for reparative dentin formation similar to primary dentin. This study may lead to the development of therapy to preserve vital pulp tissues.

Histopathological Biocompatibility Evaluation of TheraCal PT, NeoMTA, and MTA Angelus in a Murine Model.

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.