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The dental pulp is critical for physiological vitality of the tooth, and dental pulp regeneration has great potential for rebuilding live pulp tissue after pulp disease. Schwann cells (SCs) play a critical role in the support, maintenance, and regeneration of nerve fibers in dental pulp. Extracellular vesicles (EVs), which possess cell homing and tissue repair potential, derived from SCs (SC-EVs), can regulate dental mesenchymal stem cell (MSC) proliferation, multipotency, and self-renewal. However, the role of SC-EVs in dental pulp tissue regeneration remains unclear. To address this question, we treated dental pulp stem cells (DPSCs) and bone marrow stem cells (BMSC) with SC-EVs, and the results showed an obvious increase in the proliferation, migration, and osteogenic differentiation of both cell types. SC-EVs also promoted neurite outgrowth and neuron migration of rat dorsal root ganglia, as well as vessel formation in vitro. In an in vivo model of subcutaneous, SC-EVs enhanced the recruitment of endogenous vascular endothelioid-like cells and MSCs, and promoted the formation of a pulpo-dentinal complex-like structure. Finally, mass spectrometry analyses and western blot revealed that stromal cell-derived factor 1 (SDF-1, also known as CXCL12) plays a dominant role in SC-EVs. Together, these data suggest that SC-EVs successfully recruit endogenous stem cells to promote dental pulp regeneration. Our results provide a cell-free strategy for pulp regeneration that avoids the risks associated with stem cell transplantation. Statement of Significance : Dental pulp is vulnerable to infections resulting from dental care, trauma, and multiple restorations, with such infections resulting in pulpitis and pulp necrosis. The current endodontic treatment of irreversible pulp disease cannot restore the function of dental pulp and tissue engineering strategies using cell-based approaches are limited by several disadvantages, including immune rejection and limited cell sources. In this study, we found that schwann cells-derived EVs facilitated dental pulp regeneration through endogenous stem cells recruitment via SDF-1/CXCR4 axis without exogenous cell transplantation. We believe that our study makes a significant contribution to describe a cell-free strategy to promote dental pulp regeneration.

This retrospective study analyzed the 12-month pulp sensibility (cold and electric) test response after mineral trioxide aggregate (MTA) full pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis.The records of 120 subjects from 3 completed and 1 ongoing clinical study on MTA full pulpotomy were retrieved. Ninety-six first and second mandibular molar teeth with a diagnosis of symptomatic irreversible pulpitis that underwent a single-visit MTA full pulpotomy and had completed a 12-month clinical, radiographic, and pulp sensibility (cold and electric) test follow-up were included. The data were analyzed using the Fisher exact test, the Pearson chi-square test, and the McNemar test. The significance level was predetermined at P .05.A higher percentage of teeth (94.7%) responded to the electric pulp test in comparison with the cold test (13.5%) (P .05). Sex-based responses to the electric pulp test (P .05) and the cold test were similar (P .05). The age-based response was similar for the electric pulp test (P .05) but was significant for the cold test (P .05). The tooth quadrant (left and right), the tooth (mandibular first and second molar), and the location of restoration (proximal or occlusal) did not influence the response of either the electric pulp test (P .05) or the cold test (P .05). At the 1-year follow-up, all the teeth that were classified as clinically and radiographically successful responded to the electric pulp test; however, only 13 teeth responded to the cold test (P = .00).The majority (94.7%) of the teeth that underwent MTA full pulpotomy responded to the electric pulp test at a 1-year time interval.

Introduction The purpose of this study was to compare clinically and radiographically the effects of potassium nitrate in polycarboxylate cement and mineral trioxide aggregate (MTA) as pulpotomy agents in vital immature mandibular first molars. Methods The trial design was a parallel randomized, 1:1 allocation ratio, with both the participants and the data assessor blinded. A total of 50 molars of 48 eligible children aged 6–9 years were studied. The children had mandibular immature first molars with extensive caries that revealed pulp exposure during caries excavation. Patients were randomly allocated equally into 2 groups in which potassium nitrate in polycarboxylate cement (the intervention group) and MTA (the control group) were used as pulpotomy biomaterials. The treated teeth were restored permanently. The primary outcome was clinical/radiographic assessment after 1 week, 6 months, and 12 months. The secondary outcomes were radiometric analysis at 6 and 12 months to determine dimensional changes during maturogenesis. The digital radiographs were imported to image processing software to perform radiometric measurements. Data were tabulated and statistically analyzed with significance set at P ≤ .05. Results Only a single tooth failed at the 6-month recall, and another one was lost during recall in each group. Thus, the overall success rate for cases/group who finally attended the 12-month follow-up time point was 92% (23/25) with no statistically significant difference between the 2 groups. At the 12-month recall, successful cases showed root development with an increase in root length and a decrease in apical foramen width. Complete apical closure was observed in 65.2% of the roots in the intervention group and 52.1% in the control group. Conclusions The clinical and radiographic success reported in the present study reveals that potassium nitrate in polycarboxylate cement could be used as a biological and economic alternative to MTA as a pulpotomy agent in vital immature mandibular first molars. Further follow-up for longer periods is recommended.

Introduction Age-at-death estimation is an essential part of the identification process of individuals in many forensic dentistry cases where identity of the individual cannot be resolved by visual recognition or other means. Dental age estimation in adults is more of a challenge as most teeth complete their development by the age of 18 years. Aim This study aims at using the mesio-distal (MD) pulp-to-tooth ratio taken at the cervix of upper third molars (UM3) to estimate age at the time of radiographic imaging. Materials and Methods A set of 135 Cone-beam computed tomography (CBCT) radiographs of UM3s for a random sample of 135 Jordanian adults (65 females, 70 males; age range = 18–63 years, mean age = 34.4 years, SD = 11.2 years) were used. Both pulp and tooth MD diameters were measured at the cervix. MD pulp-to-tooth ratios for UM3s were correlated with age. Results Statistically significant negative moderate correlation was found between the age of the individual and the cervix MD pulp/tooth ratio (r = −0.516). This indicates that only 26.6% of the variation in age can be explained by the cervix MD pulp-to-tooth ratio. Conclusions This study concludes that cervix MD pulp-to-tooth ratio of UM3s, although apparently stronger than that of lower M3s (r = −0.361), is not a sufficiently reliable estimator of age in adults, and this is perhaps attributed to the greater variability in the time line of third molars development.

Background/purpose MTA is used to induce hard tissue regeneration in various procedures. This study evaluated the biocompatibility and mineralization potential of mineral trioxide aggregate (MTA) containing calcium fluoride (CaF2). To verify if the change of components affected physical properties, the setting time, solubility, and surface roughness were measured. Materials and methods Human dental pulp cells (HDPCs) were treated with powder and set MTA containing CaF2 (0, 1, 5, and 10 wt %). The proliferation of HDPCs was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The mineralization potential of HDPCs was investigated with the relative gene expression of alkaline phosphatase (ALP), collagen type I (ColI), osteocalcin (OCN), and runt-related transcription factor 2 (Runx2) using real-time reverse transcription polymerase chain reaction (RT-PCR). For investigating the physical properties, setting time and solubility were tested. Surface profiles of material were analyzed by a non-contact surface profiler and a scanning electron microscope (SEM). Results MTA-5% CaF2 mixtures increased the proliferation and the mineralization-related gene expression of HDPCs to a greater degree than pure MTA. The addition of CaF2 to MTA delayed the setting, but the difference was only significant in the MTA-10% CaF2. Solubility and surface roughness was not altered. Conclusion The addition of more than 5% CaF2 can be considered to increase the regeneration potential of pulp cells without adverse effects on physical property.

The aim of this case series was to describe the endodontic management of 3 immature permanent teeth that sustained traumatic injuries and subsequently presented with complete ingrowth of mineralized tissue into the canal space. Ingrowth of bone/mineralized tissue into the canal has been considered a poor long-term outcome with an inherent risk of ankylosis. In cases 1 and 2, no endodontic treatment was undertaken, except for emergency management requiring splinting. The cases were followed for 36 and 23 months, respectively. No ankylosis was evident over the review period, and normal teeth eruption was apparent. In case 1, the tooth was treated orthodontically and was responsive to pulp sensibility testing. In both cases, there was an appearance of an internal periodontal ligament–like space on the inner root wall of the canal. In case 3, 2 years postinjury, pulp necrosis and apical periodontitis occurred, and the tooth was managed with regenerative endodontic treatment consistent with the European Society of Endodontology and the American Association of Endodontists guidelines/recommendations for a regenerative procedure. The case was followed for 8 years after regenerative endodontic treatment. No ankylosis was noted with normal eruption of the teeth. The tooth was responsive to pulp sensibility testing despite the ingrowth of mineralized tissue, which was confirmed clinically.

Introduction Thorough pain assessment and thermal and mechanical testing are the primary diagnostic tools used to assess the status of pulp and periapical tissues in teeth with potential endodontic pathology. This study evaluated predictors of acute odontogenic pain to better understand the relationship between endodontic pain, clinical testing, endodontic disease, and diagnoses. Methods Participants (N = 228) presenting with acute odontogenic pain underwent standardized clinical testing and reported their pain intensity. Univariate and multiple regression analyses were performed to evaluate the predictors of acute endodontic pain. Chi-square tests with Bonferroni adjustments were conducted to measure the frequency of endodontic diagnostic test findings and clinical observations in patients with different pulpal diagnoses. Results A negative response to cold stimulation on the causative tooth and percussion hypersensitivity on the healthy adjacent tooth were the strongest predictors of higher levels of acute endodontic pain. Percussion hypersensitivity on the healthy adjacent tooth was present in a quarter of the cohort and was reported with equal frequency in teeth diagnosed with irreversible pulpitis, necrotic pulp, and previously initiated/treated teeth. Although painful percussion on the causative tooth was more frequently reported in teeth diagnosed with necrotic pulp, painful palpation was more frequently reported on teeth diagnosed with previously initiated/treated teeth. Conclusions Percussion hypersensitivity on the healthy adjacent tooth may reveal a lowered pain threshold and heightened pain sensitization. It is also possible that the 2 commonly performed mechanical sensory tests, percussion and palpation hypersensitivity, may detect different aspects of endodontic pathophysiology and pain processing.

Dens invaginatus (DI), which often occurs in the maxillary lateral incisor, is an important issue in endodontics because the treatment complexity increases depending on the degree of invagination and the vitality or nonvitality of the pulp. An 11-year-old female patient with a sinus tract in the gingiva of the maxillary lateral incisors showed peri-invagination periodontitis and double DI on radiography. Cone-beam computed tomographic imaging was used to examine the structure in the root canal in detail, and Oehlers type IIIA and IIIB DI was found. It was also shown that the patient’s bone defect was caused by type IIIA. Because a healthy reaction was observed in the pulp test, the final diagnosis was peri-invagination periodontitis associated with type IIIA of the double DI with vital pulp. We expected the lesion to heal by treating only the type IIIA invaginated pseudo–root canal while preserving the healthy pulp. The invaginated root canal was cleaned under a microscope using ultrasonic instruments and nickel-titanium files to minimize irritation to the pulp. Because the lesion shrinkage was confirmed by cone-beam computed tomographic imaging taken 3 months after the start of treatment, vertical compaction of the warm gutta-percha technique was performed. At the 6-month postoperative recall, the pulp was normal, and the lesions were further improved. Treatment of the main root canal of double DI is complicated. However, proper diagnosis and careful cleaning of the invaginated root canal are essential for healing while preserving the pulp.

Introduction Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are thermosensitive channels that play an important role in thermal sensation or tooth pain by regulating intracellular Ca2+ concentration that is essential for pulp tissue repair. The aim of this study was to evaluate the role of TRPA1 and TRPV1 channels in the odontogenic differentiation of human dental pulp cells (HDPCs). Methods HDPCs were isolated from healthy human intact third molars and cultured in odontogenic differentiation medium. Gene and protein expression levels of TRPA1 and TRPV1 channels during the odontogenic differentiation of HDPCs were evaluated by real-time quantitative polymerase chain reaction and Western blot analysis. HDPCs were then treated with channel agonists or antagonists, and the expression levels of odontogenic markers dentin sialophosphoprotein (DSPP) and osteopontin (OPN) were examined. Alkaline phosphatase activity and alizarin red staining were also conducted to detect mineralization levels. Results Consistent with the mineralization degree and DSPP and OPN expression, messenger RNA and protein expression of TRPA1 and TRPV1 channels was up-regulated during the odontogenic differentiation of HDPCs. The application of TRPA1 or TRPV1 agonists increased the mineralized nodules of alizarin red staining and alkaline phosphatase activity and up-regulated the messenger RNA and protein expression of DSPP and OPN, respectively, with the highest values reached on the seventh day (P Conclusions TRPA1 and TRPV1 channels not only showed up-regulated expression along with the odontogenic differentiation of HDPCs but also could affect the odontogenic differentiation by regulating intracellular Ca2+ concentration.

Background/purpose Effective regulation of the inflammatory process is essential for pulp repair and regeneration. Meloxicam has anti-inflammatory activity in systemic administration. The purpose of this study is to observe effects of topically applied meloxicam on inflamed pulp and to explore its potential value in the treatment of pulpitis. Materials and methods The coronal pulp tissues of rat molars were stimulated with 10 mg/mL lipopolysaccharide (LPS group) and then treated with 500 μmol/L meloxicam (meloxicam group). The untreated pulp tissues were used as the control group. After 3 h of incubation in vitro, the gene expression of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in each group was detected by real-time RT-PCR. The pulp tissues of each group were randomly subcutaneously implanted into nude mice, and 500 μmol/L meloxicam was injected into the subcutaneous pocket of the meloxicam group. Haematoxylin eosin staining, Masson staining and immunohistochemical staining were performed on samples after 3 days and 4 weeks retrieval, respectively. Results Compared with the LPS group, the mRNA expression levels of TNF-α and IL-6 of the meloxicam group were significantly reduced in vitro. The inflammatory response and cyclooxygenase-2 expression of the meloxicam group were decreased, and osteodentin-like tissue was generated in the pulp cross section of the meloxicam group in vivo. Conclusion The topical application of meloxicam inhibits the inflammatory response of inflamed pulp and further promotes the formation of osteodentin-like tissues but fails to induce the formation of the pulp–dentin complex. Topically applied meloxicam has the potential to regulate pulp inflammation.

Made available in DSpace on 2021-06-25T11:00:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Introduction: Guided tissue regeneration has been considered a promising biological strategy to replace conventional endodontic therapies of teeth with incomplete root formation. Therefore, in the present study, a collagen/gelatin hydrogel either containing dosages of fibronectin (FN), or not, was developed and assessed concerning their bioactive and chemotactic potential on human apical papilla cells (hAPCs). Methods: Hydrogels were prepared by varying the ratio of collagen and gelatin (Col/Gel; v/v), and used to establish the following groups: Collagen (positive control); Col/Gel 4:6; Col/Gel 6:4; Col/Gel 8:2. The viability, adhesion, and spreading of cells seeded on the hydrogels were evaluated. Different concentrations of FN (0, 5, or 10 μg/mL) were incorporated into the best formulation of the collagen/gelatin hydrogel selected. Then, the hAPCs seeded on the biomaterials were assessed concerning the cell migration, viability, adhesion and spreading, and gene expression of ITGA5, ITGAV, COL1A1, and COL3A1. Results: The Col/Gel 8:2 group exhibited better cell viability, adhesion and spreading in comparison with Control. Higher values of hAPC migration, viability, adhesion, spreading and gene expression of pulp regeneration markers were found, the higher the concentration was of FN incorporated into the collagen/gelatin hydrogel. Conclusion: Collagen/gelatin hydrogel with 10 μg/mL of FN had potent bioactive and chemotactic effects on cultured hAPCs. Department of Dental Materials and Prosthodontics Araraquara School of Dentistry Univ. Estadual Paulista – UNESP Department of Operative Dentistry Endodontics and Dental Materials Bauru School of Dentistry University of São Paulo Departament of Orthodontics and Pediatric Dentistry Araraquara School of Dentistry São Paulo State University (Unesp) Department of Physiology and Pathology Araraquara School of Dentistry São Paulo State University (Unesp) Department of Dental Materials and Prosthodontics Araraquara School of Dentistry Univ. Estadual Paulista – UNESP Departament of Orthodontics and Pediatric Dentistry Araraquara School of Dentistry São Paulo State University (Unesp) Department of Physiology and Pathology Araraquara School of Dentistry São Paulo State University (Unesp) CNPq: 302047/2019–0 CNPq: 408721/2018–9

Human-derived composite amnion-chorion membrane (ACM) has been used for various regenerative treatments. The aim of this pilot study was to investigate the effectiveness of the ACM as a scaffold for pulp regeneration in mature canine teeth.A total of 24 roots from mature premolars in dogs were included for regenerative procedures using blood clots (BC) (group 1, n = 8), collagen membrane (CM) (group 2, n = 8), and ACM (group 3, n = 8). Each tooth was left open through a buccal access to induce root canal infection and inflammation. The root canals were disinfected with 1.5% NaOCl and calcium hydroxide intracanal medicament. After 2 weeks, bleeding was evoked to induce blood clot formation (group 1) or before the placement of the membranes (groups 2 and 3). After 12 weeks, the animals were euthanized for histologic assessment. The histologic data including intracanal fibrous connective tissue, odontoblast-like cell lining, intracanal mineralized tissue, periapical inflammation, and apical closure were qualitatively and quantitively analyzed.Histologic analysis revealed that intracanal fibrous connective tissue was identified in all groups, but a higher volume of the fibrous tissues was formed in the ACM group. Odontoblast-like cells were only observed in the ACM group. The intracanal mineralized tissue was observed only in the BC and CM groups. The BC group showed more periapical inflammation than the ACM group (P .05). Apical closure was more often found in the CM group than the BC group (P .05).More intracanal fibrous tissue and odontoblast-like cell lining, and less periapical inflammation were observed after regenerative endodontic treatment in mature teeth using the ACM than blood clot alone or blood clot with collagen membrane. The use of the ACM may be useful for a cell-homing-based pulp regeneration in mature teeth.

Maxillary transverse deficiency is a common skeletal problem. When the patient is younger, it is treated by rapid palatal expansion by using orthodontic appliances. If this fails or the patient is older, which means skeletal growth is completed, surgically aided rapid palatal expansion (SARPE) becomes necessary. In this technique, after the osteotomies have been made, the two maxillary bones are distracted by tooth-borne device. Since a tooth-borne device will apply the distraction forces on the teeth, the pulp volumes may change. Our aim was to investigate the volume changes of the tooth pulps after SARPE in which a tooth-borne device was used. We scanned our database and included 20 patients (7 males and 13 females) aging between 16 and 30 (mean 19.5±3.97) to this retrospective study. All the patients had undergone SARPE surgeries and they had pre-surgery and postconsolidation cone beam computerized tomography (CBCT) images. All the surgeries had been done in similar ways; all the patients had used similar tooth-borne modified acrylic bonded expansion device. We divided the maxillary teeth into three groups: the incisors, the premolars and the molars. We imported the CBCT images of each patient into 3D Slicer software. We calculated volumes of pulps for all maxillary teeth. We compared volumes with paired t test. Statistical significance level was accepted as P< .05. The devices had been left in place between 83 and 179 days including distraction and consolidation periods (mean 121.35±27.83 days). Amount of the expansions varied between 6.03mm and 11.16mm (mean 7.19±1.18mm). We found a statistically significant decrease of the pulp volumes in incisor, premolar and molar teeth (P

Objective Dentinogenesis imperfecta (DI) requires dental treatment. This study investigated the characteristics of DI teeth associated with osteogenesis imperfecta (OI) and COL1A2 mutations. Study Design Whole exome and Sanger sequencing were performed. Three primary teeth (called “OIDI teeth”) obtained from 3 unrelated COL1A2 patients were investigated and compared with 9 control teeth from age-matched healthy individuals using colorimetry, micro–computed tomography, Knoop microhardness, energy dispersive X-ray spectroscopy, scanning electron microscopy, and histology. Results All patients were identified with heterozygous glycine substitutions in COL1A2. The COL1A2 mutations, c.1531G>T and c.2027G>T, were de novo, whereas c.3106G>C was inherited. OIDI1, 2, and 3 teeth had a substantial decrease in dentin microhardness and lightness. OIDI2 enamel microhardness was significantly reduced, whereas OIDI1 and 3 had enamel microhardness comparable to that of control individuals. The OIDI1 pulp cavity was large; OIDI2 was narrow; and OIDI3 was obliterated. OIDI1 and 3 had significantly higher carbon levels than those in control individuals. Numerous ectopic calcified masses, sparse and obstructed dentinal tubules, dentin holes, and collagen disorientation were observed. Conclusions OIDI teeth had reduced lightness and variable pulp morphology. Weak dentin, mineral disproportion, and abnormal ultrastructure could contribute to the brittleness of OIDI teeth and adhesive restoration failure. Here, we expand the phenotypic spectrum of COL1A2 mutations and raise awareness among dentists seeing patients with OI.

Angiogenesis is critical for tissue healing and regeneration. Promoting angiogenesis in materials implanted within dental pulp after pulpectomy is a major clinical challenge in endodontics. We demonstrate the ability of acellular self-assembling peptide hydrogels to create extracellular matrix mimetic architectures that guide in vivo development of neovasculature and tissue deposition. The hydrogels possess facile injectability, as well as sequence-level functionalizability. We explore the therapeutic utility of an angiogenic hydrogel to regenerate vascularized pulp-like soft tissue in a large animal (canine) orthotopic model. The regenerated soft tissue recapitulates key features of native pulp, such as blood vessels, neural filaments, and an odontoblast-like layer next to dentinal tubules. Our study establishes angiogenic peptide hydrogels as potent scaffolds for promoting soft tissue regeneration in vivo. STATEMENT OF SIGNIFICANCE: A major challenge to endodontic tissue engineering is the lack of in situ angiogenesis within intracanal implants, especially after complete removal of the dental pulp. The lack of a robust vasculature in implants limit integration of matrices with the host tissue and regeneration of soft tissue. We demonstrate the development of an acellular material that promotes tissue revascularization in vivo without added growth factors, in a preclinical canine model of pulp-like soft-tissue regeneration. Such acellular biomaterials would facilitate pulp revascularization approaches in large animal models, and translation into human clinical trials.

Introduction This study evaluated the pulp response to periodontal disease of increasing severity. Methods The material comprised human teeth affected by moderate (n = 16) to severe (n = 48) periodontal disease and no clinically identified caries lesions. Specimens were obtained by extraction and were processed for histopathologic and histobacteriologic methods. Results In 13 of 16 teeth with moderate periodontal disease and vital pulp, no frank accumulations of inflammatory cells were observed. In 22 of 32 teeth with severe periodontal disease and vital pulps, no distinct inflammatory cell accumulations were observed in any portion of the pulp when there was an intact or minimally damaged cementum layer in the corresponding areas. Intravascular bacterial aggregations were detected in pulp blood vessels in 6 teeth with symptomatic pulpitis and severe periodontal disease, which had not reached the root apex in 4 of them. Focal areas of infection and varying accumulations of acute and chronic inflammatory cells were observed throughout the pulp tissue and surrounding these infected blood vessels. When the periodontal pocket reached the apex of single-rooted teeth, the entire canal space was necrotic and colonized by bacteria, often forming biofilms. In multirooted teeth, the pulp response varied according to the root(s) affected. Intrapulpal calcifications were observed in 91% of the teeth. The pulp and cementum of the control teeth showed no pathologic changes or bacteria. Conclusions The pulp showed a significantly detectable response when the cementum coverage was lost or when the periodontal pocket reached the root apex. In the former condition, the pulp response was usually discrete, whereas in the latter, severe reactions usually developed. In some teeth, vessels with a compromised blood flow may serve as avenues for bacteria to invade the pulp via apical or lateral foramina. This indicates that in some teeth the pulp may undergo severe inflammation and necrosis even before the periodontal disease reaches the apical root segment.

Because of the unique encasement of the human dental pulp in a low-compliance environment, intrapulpal tissue pressure is of paramount importance in pulpal physiology. Tissue pressure is a local phenomenon, and the pathophysiology of pulp is characterized not by a sudden strangulation at the apex but by a circumferential spread of inflammation and necrosis from a site of initial injury. It is only when gross destruction of tissue has led to a loss of structural integrity that the pulp may become an isobaric chamber in which all areas are in hydrostatic communication.

Introduction The differentiation of dental pulp cells (DPCs) plays an important role in the repair of dental pulp injury. Bone morphogenetic protein 9 (BMP9) is one of the most effective BMPs to induce the differentiation of stem cells. However, the role of BMP9 in promoting the odontogenic differentiation of DPCs and dentinogenesis is worth knowing. Methods Fluorescence in situ hybridization and immunohistochemistry staining were performed to detect the BMP9 expression in human dental pulp. BMP9 was overexpressed in human DPCs (hDPCs), and the mineralization of hDPCs was tested by alkaline phosphatase staining and alizarin red staining. The expression of odontogenic differentiation-related genes was examined by quantitative real-time polymerase chain reaction and western blotting. The subcutaneous transplantation experiment was performed to test the odonto-induction ability of BMP9 in vivo. The rat direct pulp-capping experiment was performed to test the function of BMP9 in promoting dentin formation. Results BMP9 showed an increased expression in odontoblast layer at both the mRNA and protein levels. BMP9 enhanced the mineralization and induced the expression of odontogenic differentiation-related genes in hDPCs. More mineralized nodules, and increased expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP1) were detected in the beta-tricalcium phosphate scaffold/cells composites of BMP9 group compared with the control group. Meanwhile, there was thicker reparative dentin formation in the BMP9 group in the rat pulp exposure experiment. Conclusions BMP9 participates in the process of DPC differentiation and promotes DPC mineralization and dentinogenesis. BMP9 might be a potential therapeutic target in the repair of dental pulp injury.

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.

Background and Overview Orthodontic miniscrews have become popular tools for providing temporary anchorage during orthodontic treatment. Although they are easy to insert, damage to the periodontal ligament or dental root during insertion is an unfavorable iatrogenic complication. Root perforation during miniscrew insertion in human teeth has been reported in a few articles. In this article, the authors describe the spontaneous repair of an iatrogenic root perforation in a mandibular first molar that occurred during insertion of an orthodontic miniscrew in a young girl undergoing orthodontic treatment. Case Description A 15-year-old girl with malocclusion was undergoing orthodontic treatment when the mesial root of her mandibular right first molar was damaged by an orthodontic miniscrew. The miniscrew and corresponding bracket were immediately removed to avoid any unnecessary forces on the tooth. Because the pulp remained vital without any additional damage and infection for 6 months, orthodontic treatment was resumed and completed in 9 months without any pulp damage or unfavorable symptoms. Serial periapical radiographs and cone-beam computed tomographic images showed that the injured area was surrounded by reparative tissue without any apical lesion. Conclusions and Practical Implications The findings of this case suggest that immediate removal of unnecessary forces provides an environment for spontaneous repair in cases of iatrogenic root perforation by orthodontic miniscrews, even when the damage involves the pulp. If force stimulation is avoided for a certain period, which was 6 months in this case, it may be possible to complete the orthodontic treatment without unfavorable symptoms.

Introduction Previous studies have shown that in teeth presenting with symptoms of irreversible pulpitis (IP), bacteria and their by-products driving inflammation are confined mainly within the coronal pulpal tissue. The present study aimed to determine the presence and identity of bacteria within pulps presenting with clinical symptoms of IP using molecular methods. Methods Samples were obtained from 30 adult patients presenting to the dental emergency department with signs and symptoms of IP. After meticulous surface decontamination, the pulp space was accessed, and clinical samples were collected from inflamed pulp tissue using sterile paper points. Genomic DNA was extracted from the clinical samples, and quantification of bacteria was performed using quantitative polymerase chain reaction targeting the conserved 16S ribosomal RNA (rRNA) gene. To characterize the microbial composition, the V3–V5 hypervariable regions of the 16S rRNA gene were amplified and subjected to next-generation sequencing on the MiSeq platform (Illumina, San Diego, CA). Results Of the 30 teeth that presented with IP, half of the intracanal samples had a substantial bacterial load (16S rRNA copies) within the IP vital pulp as determined by quantitative polymerase chain reaction. Next-generation sequencing microbial identification was successful in 7 intracanal samples and yielded 187 bacterial operational taxonomic units within the IP samples. The most abundant genera observed among the vital cases were Veillonella (16%), Streptococcus (13%), Corynebacterium (10%), Cutibacterium (9.3%), and Porphyromonas (5.7%). Conclusions The current study highlighted the evidence of vital teeth diagnosed as IP harboring considerable bacterial loads and composed of genera reflective of established endodontic pathology and thus may offer insights into the initial events preceding pulpal necrosis.

Objectives Selective caries removal (SCR) is recommended over non-selective removal for managing deep carious lesions to avoid pulp exposure and maintain pulp vitality. During SCR, residual carious dentin is left behind and sealed beneath the restoration. The biomechanical effects of such residual lesions on the restored tooth remain unclear and were assessed using finite element modeling (FEM). Methods Based on μ-CT images of a healthy permanent human third molar, we developed five finite element models. Generic class I and II cavity restorations were modeled where residual lesions of variable sizes were either left or fully removed on occlusal and proximal surfaces. The cavities were restored with adhesive composite. All 3D-FE models were compared with a model of a healthy, non-treated molar. A vertical load of 100 N was applied onto the occlusal surface. Results Regardless of the lesion size, in molars with occlusal lesions higher mean stresses were predicted along the filling-lesion interface than in all other models. The smallest occlusal lesion (O1 = 1 mm) resulted in the highest maximum stresses at the filling-lesion interface with large stress concentrations at the filling walls indicating failure risk. In conclusion, lesion site and extent are influencing parameters affecting the filling-lesion interactions and thus the biomechanical behavior of the tooth after SCR. Significance Retaining carious lesions around the pulpal floor affects the deformation and stress states in tooth-filling complexes. The higher stresses observed in molars with occlusal lesions may affect restoration stability and longevity. Suprisingly, more extended occlusal lesions may provide a more favorable tooth performance than less extended ones. In contrast, in molars with proximal lesions the residual lesion had only limited effect on the tooth’s biomechanical condition.

The polymerization of acrylic resin materials used for the direct fabrication of anterior deprogramming devices results in a temperature increase because of the exothermic reaction. This heat release might cause thermal trauma to the pulp, compromising the tooth's vitality.The purpose of this in vitro study was to compare the temperature increase and the timing of the maximum temperature recording obtained inside the pulp chamber of a maxillary central incisor during the polymerization of different resins materials used for the direct fabrication of anterior deprogramming devices.The exothermic reaction was examined during the polymerization of 4 different polymethyl methacrylate resin products: Pattern Resin LS; GC America, DuraLay inlay pattern resin; Reliance Dental, Kallocryl CPGM red; Speiko, and mega-Model Resin NF; Megadental. A polymeric matrix was fabricated to simulate the anterior deprogramming device. A freshly extracted intact maxillary central incisor was fixed in an acrylic resin mold, and a thermal probe was inserted into the pulp chamber to transmit the temperature recordings. The resin materials were mixed as per the manufacturer's instructions and an equal volume of each was inserted into the plastic matrix, which was then positioned on the tooth. The temperature increase and the time needed to obtain the maximum temperature were recorded. The temperature and time recordings were performed initially for the intact tooth and repeated after the tooth was prepared for a metal-ceramic restoration. The data were analyzed with descriptive statistics, 1-way analysis of variance, and the Tukey Honestly Significant Difference tests (α=.05).In accordance with the 1-way ANOVA, there was a statistically significant difference both in temperature increase (F [7,72] = 3.72, P=.002) and in the recorded time (F [7,72] = 160.80, P.001). The mean temperature inside the pulp chamber ranged from 40.1 °C for the Pattern Resin LS to 41.4 °C for the DuraLay inlay pattern resin material. The mean time recordings ranged from 133 seconds for the Kallocryl CPGM red material to 266 seconds for the DuraLay inlay pattern resin material.The Pattern Resin LS revealed the lowest exothermic reaction (P.05) when compared with the other materials tested in this study, whereas Kallocryl CPGM red had the shortest time increase without being statistically significantly different.

Introduction This prospective study evaluated the outcome of a combination of nonsurgical endodontic (NSET) and vital pulp therapy (VPT) for the management of mature permanent mandibular molar teeth with symptomatic irreversible pulpitis (SIP) and apical periodontitis (AP). Methods Institutional ethical clearance was obtained. Mandibular molar teeth (N = 60) with a definitive diagnosis of SIP and AP with a radiographic periapical index score (PAI) of ≥3 in either 1 of the roots (mesial or distal) were included. Block randomization was used for allocation. In the NSET group (n = 30), single-visit NSET was performed using a standardized operating protocol. In the NSET-VPT group (n = 30), subsequent to full pulpotomy, at the root orifice where a vital pulp was observed (as determined by the arrest of pulpal bleed upon application of a 2.5% sodium hypochlorite pressure pack), a mineral trioxide aggregate radicular barrier was placed, and it was covered with light-cured resin-modified glass ionomer cement. NSET was performed in the root exhibiting a PAI score ≥3. The tooth was permanently restored. Postoperative pain was assessed at 24, 48, and 72 hours. Teeth were followed up clinically and radiographically at 12 months. The presence/absence of symptoms and the change in PAI scores were noted. The data were statistically analyzed. Results The success rate was 90% in the NSET group and 93.3% in the NSET-VPT group. According to an intergroup comparison between the proportion of teeth healed and nonhealed (radiographic), there was no significant difference (P > .05). Conclusions The combination of NSET and VPT is a viable biologically based minimally invasive treatment option for multirooted mandibular teeth with SIP and AP.

In-depth knowledge of common and aberrant pulp morphology is essential for appropriate diagnosis and treatment planning prior to commencing root canal treatment. Radicular morphology of mandibular premolars has been extensively studied. Considerable variation in the number of canals and roots found in these teeth has been reported. Aim The purpose of this study is to investigate the root and root canal morphology of mandibular first premolar among Saudi Arabian subpopulation in Aseer using CBCT. Methods Cone-beam computed tomography images of Mandibular first premolar were taken from 166 patients which were referred to Armed Forces Hospitals Southern Region (AFHSR), Khamis Mushayt, Asir region Saudi Arabia. All the images were assessed by two Evaluators (An Endodontist and a Radiologist). Inter-examiner reliability was determined and was assessed by KAPPA value. Results The mandibular first premolar (n = 216) distributed as 120 teeth in female and 96 teeth in male. Out of the 120 teeth examined in female groups one canal was seen in 95 (79.2%) teeth, two canals in 19 (15.8%) teeth and three canals in 6 (5%) teeth where as in the Male group out of 96 teeth, 52 (54.1%) teeth showed one canal, 32 (33.3%) teeth with two canals whereas 12 (12.5%) teeth showed presence of three canals. Chi-Square test for mandibular first premolars demonstrated the chance of second canal in the mandibular first premolar more in male than female and these differences was statistically significant (P ≤ 0.05). Conclusion Endodontic therapy of mandibular premolars is a challenge for clinician because of their frequent morphological and anatomical abnormalities. Proper knowledge about number of root canals and canal configuration is a key to success in Endodontic. There is a great variability in different population regarding the root canal configuration in mandibular pre-molars. However, most studies state the mandibular first premolar has one root canal. Also, the most prevalent type of root canal found was Type I vertucci.

Introduction Vital pulp therapy aims at preserving pulp vitality and regenerating dentin. Therefore, the purpose of this study was to explore the effects of a combination of treated dentin matrix (TDM) proteins and dental pulp cell (DPC)-derived small extracellular vesicles (sEVs) on pulp-dentin complex repair. Methods We prepared TDM by chemical demineralization and mechanical disruption of teeth to a powder preparation. The sEVs were isolated from culture supernatants of DPCs and identified by nanoparticle tracking analysis, Western blotting, and transmission electron microscopy. The effect of a combination of TDM proteins and DPC-derived sEVs on DPC proliferation, migration, and odontogenic differentiation was evaluated in vitro. A minipig model of pulp injury was used to compare the clinical outcomes and tissue responses attributed to 4 materials including TDM, sEV-TDM, sEVs, and mineral trioxide aggregate. Results The sEV isolated from the cell supernatant promoted DPC proliferation and migration. The combination of TDM extracts and sEV synergistically promoted the migration of DPCs but suppressed their proliferation. Real-time polymerase chain reaction and Western blot revealed that sEV-TDM enhanced the odontoblast-related protein expressions in DPCs. In in vivo studies, TDM and sEV-TDM promoted the formation of continuous reparative dentin. Furthermore, odontoblastlike high columnar cells were observed on the pulp side of the dentin bridge. Conclusions The sEV-TDM complex exhibits intrinsic biological activities, which has potential applications as a bioactive pulp-capping material.

Background/purpose Dental pulp stem cells can be isolated from human teeth with deep caries (cDPSCs), but their biological characteristics are still unclear. The aim of this study was to investigate the angiogenic potential of cDPSCs and compare them to dental pulp stem cells from human normal teeth (nDPSCs). Materials and methods Cells were isolated from human pulp tissue of normal and infected teeth with deep caries. Basic mesenchymal stem cell (MSC) characterization was conducted. Colony forming units and proliferation ability were evaluated in nDPSCs and cDPSCs. Expression of VEGF in both tissues and cells was examined by immunohistochemical staining. After stimulating nDPSCs and cDPSCs with an angiogenic medium, angiogenic markers were evaluated by qRT-PCR and western blotting. Finally, tube formation assays were used to evaluate the in vitro angiogenesis potential of both cell populations. Results Both nDPSCs and cDPSCs possessed typical MSC characteristics. cDPSCs had enhanced colony formation and proliferation capacities than nDPSCs did. The expression of VEGF was higher in pulp tissue from teeth with deep caries and cDPSCs than in normal tissue and nDPSCs. When both cell types were grown in vitro under angiogenic conditions, cDPSCs expressed a higher level of angiogenic markers and showed a stronger angiogenesis potential than nDPSCs did. Conclusion cDPSCs maintained MSC traits and presented a higher angiogenesis potential than nDPSCs.

The study of regenerative dentistry receives a fast growing interest. The potential ability of the dentin-pulp complex to regenerate is both promising and perplexing. To answer the challenging nature of the dental environment, scientists have developed various combinations of biomaterial scaffolds, stem cells, and incorporation of several growth factors. One of the crucial elements of this tissue engineering plan is the selection and fabrication of scaffolds. However, further findings suggest that cell behavior hugely depends on mechanical signaling. Nanotopography modifies scaffolds to alter cell migration and differentiation. However, to the best of the author's knowledge, there are very few studies addressing the correlation between nanotopography and dentin-pulp complex regeneration. Therefore, this article presents a comprehensive review of these studies and suggests a direction for future developments, particularly in the incorporation of nanotopography design for dentin-pulp complex regeneration., Highlights • Nanotopographical size and forms affects different dental pulp stem cell's response. • Dental pulp stem cell responses both molecular and mechanical cues from the environment. • The nanotophography of scaffold generates mechanotransduction on dental pulp stem cell. • Mechanotransduction is related to gene expression, arrangement, and morphological changes of dental pulp stem cell. • Smaller size nanotopography tends to enhance cell attachment; the larger one increases differentiation and proliferation.

Introduction Patients seeking endodontic treatment commonly present with reduced mechanical pain thresholds (ie, mechanical allodynia [MA]) in the offending teeth. In patients with moderate to severe pain, MA may manifest in the teeth contralateral to the offending teeth because of the onset of central sensitization (CS). We hypothesize that there are quantitative differences in MA and CS in patients with different pulp and periradicular diagnoses. Methods Patients (n = 70) receiving endodontic treatment in the graduate endodontic clinic at the University of Texas Health Science Center at San Antonio and healthy volunteers (n = 10) were included in this cross-sectional study. The mechanical pain threshold from molar teeth was measured by a digital bite force transducer on the offending tooth (ipsilateral) and the contralateral tooth. Ipsi- and contralateral MA among different endodontic diagnoses were analyzed using the Kruskal-Wallis with Dunn post hoc test and the Student t test for differences between sexes. Multivariate regression models analyzed predictors for MA and CS. Results Periradicular diagnoses of asymptomatic apical periodontitis, symptomatic apical periodontitis, and chronic apical abscess cases were significantly associated with MA. CS, seen as contralateral MA, was only detected in pulpal diagnosis of symptomatic irreversible pulpitis, previously initiated treatment, symptomatic apical periodontitis, and chronic apical abscess. Females experienced significantly lower pain thresholds than males on both sides. MA and CS were significantly correlated in both sexes. The preoperative pain level and duration were significant predictors for MA and CS only in female patients. Lastly, age was a significant predictor for MA in females. Conclusions The magnitude of MA and CS varied with different endodontic diagnoses, with CS being correlated with increases in MA. Only in female patients were age, preoperative pain duration, and intensity significant predictors for the development of MA and CS.

The efficiency of extracts with antioxidant properties of plum pulp, black tea and green tea leaves was evaluated, analyzing the induction periods (IP) and rate constants (k) at 110 °C, in the 1st, 30th, 57th an 91st day of storage. Antioxidant activity was observed in all extracts, either by the rat constant decreased or by the induction period increase. The higher induction period obtained was 9.15 h for the black tea leaves extract while the lower was 6.97 h for the green tea leaves extract. The control had an average induction period of 6.95 h for the first day. The models obtained are significant and showed determination coefficients greater than 0.90 with no significance lack of fit at the level of 5%. The optimization with maximization of the induction period and minimization of the rate constant showed that the black tea extract was the most suitable to avoid oxidation. On the first day of test, the optimization indicates the mixture containing 50% of black tea and 50% of plum pulp extract as the best mixture. The optimizations provided a variation of 8.92

External root resorption (ERR) is often a complication of traumatic injury to the teeth. Traditionally, external inflammatory root resorption is treated with calcium hydroxide. The outcome of ERR, especially replacement resorption, is unpredictable. The purpose of the present case report was to describe regenerative endodontic procedures (REPs) for 1 replanted avulsed tooth with severe external root resorption and root perforation (tooth #9) and 1 extruded tooth (tooth #8). A 9-year-old girl was referred for the treatment of teeth #8 and #9 4 months after the initial trauma. Clinical examination showed that tooth #9 had a sinus tract present near the periapical area, was tender to percussion and palpation, and did not respond to pulp sensibility tests. Tooth #8 responded to pulp sensibility tests. Periapical radiographic and cone-beam computed tomographic examination showed that tooth #9 had a periapical radiolucent lesion and severe ERRs with a root perforation. Tooth #9 was diagnosed with a necrotic pulp and symptomatic apical periodontitis. Regenerative endodontic procedures (REPs) were initiated. Tooth #8 became nonresponsive to pulp sensibility tests and developed a periapical lesion 12 months after REPs of tooth #9 and was also treated with REPs. The clinical symptoms and apical lesions resolved for both teeth after REPs. The severe ERRs were arrested, and root perforation was repaired for tooth #9. Teeth #8 and #9 underwent canal obliteration by hard tissue formation after REPs and were in function at 18 months and 30 months, respectively. REPs may be used to manage traumatized immature permanent teeth with a necrotic pulp and apical periodontitis associated with severe ERR and root perforation.

Purpose Fingertip injuries are common in the industrial and factory workers as well as in the domestic settings. Loss of pulp hampers daily life activities. Functional and aesthetic aspects are important in fingertip reconstruction. The bone is usually exposed along with soft tissue loss. Therefore to reconstruct the pulp flap with adequate bulk is required. Methods We are reporting a case series of 12 patients with the injury over the volar aspect of distal phalanx of the index or middle finger. In all cases laterally based thenar flap was chosen. The flap donor site was closed primarily in most of cases, while 4 patients required skin graft. The flap was detached in between 2-3 weeks. Functional assessment was done using static and dynamic 2-point discrimination and range of motion at each joint. The aesthetic outcome was assessed through questionnaire. The results were analyzed using the unpaired t-test (SSPS version 21). Results Partial necrosis occurred in 2 cases while rest of flaps survived successfully. Static 2-point discrimination ranged from 6-10 mm with mean 8.6 mm and dynamic 2-point discrimination ranged from 8-10 mm with mean 8.9 mm. Mean satisfaction score was (4.0±0.55). Conclusion Thenar flap is a good choice for reconstruction of the finger pulp as it provides the bulk with good functional and aesthetic outcome.

Introduction The purpose of this in vitro study was to determine whether the methods used to treat endodontically and to restore anterior immature teeth with a necrotic pulp influence their resistance to fracture. Methods Following access opening and cleaning and shaping, 80 specimen teeth were assigned into 5 groups according to the endodontic obturation method and coronal restoration: A1 – apexification with a composite restoration in the crown area, A2 – apexification with a composite restoration in the crown and 3 mm into the root, group IR – immediate revascularization with a composite restoration in the crown area, group SR – successful revascularization with a composite in the crown area, and control group (CG) – mature tooth treated with gutta percha and sealer with a composite restoration in the crown area. The teeth were mounted in acrylic blocks and brought to fracture under compressive forces in a universal testing machine. Both the fracture strength and the location where the fracture occurred were recorded. Results There were no statistically significant differences in the fracture resistance among the 5 groups (one-way ANOVA, F = .545, df = 4, p = .703). No statistically significant differences were found in the location where the fracture occurred either (X2=4.1 df=4 p=.391). Conclusions Within the limitations of this in vitro study, it can be concluded that the treatment options used to treat non-vital immature teeth provided the same resistance to fracture.

To evaluate the influence of light emitted from two Polywave®, LED light-curing units (LCU) on in vivo pulp temperature (PT) rise and signs of acute inflammatory response in pulps of human premolar having deep Class V preparations.Sixty intact, first premolars from 15 volunteers requiring extraction received infiltrative anesthesia. A sterile thermocouple probe was inserted within the pulp tissue through a minute occlusal pulp exposure in only 45 teeth (n = 9) to continuously monitor PT (°C). A deep buccal Class V preparation was created, and the surface was exposed to light from a commercial Polywave LCU (Bluephase 20i (20i), Ivoclar Vivadent) or from an experimental LCU (Exp) using the exposure modes (EM): 1s/Exp and 2s/Exp, 10s/20i, 20s/20i, and 60s/20i. Peak PT and PT rise values above baseline (ΔT) data were evaluated using a one-way ANOVA followed by Tukey's post-hoc test (α = 5%). Teeth used for histological and immunohistochemical analyses (n = 3) were extracted approximately 2 h after exposure to the LCU.No significant difference in peak PT and ΔT values was noted between 2s/Exp and 20s/20i groups, which both exhibited higher values than 1s/Exp and 10s/20i groups (p0.001). Dilated and congested blood vessels were seen after exposure to 1s/Exp, 2s/Exp, or 60s/20i EMs. The expression of IL-1β and TNF-α tended to be more intense when higher irradiance was delivered.Although higher irradiance delivered over a short exposure caused lower PT rise than 5.5 °C, such EMs should be used with caution, as they have more potential to harm the pulp tissue.

Dental pulp, plays an indispensable role in maintaining homeostasis of the tooth. Pulp necrosis always causes tooth nutrition deficiency and abnormal root development, which leads to tooth discoloration, fracture or even loss. Our previous study showed implantation of autologous SHED could regenerate functional dental pulp. However, the detailed mechanism of the implanted SHED participating in dental pulp regeneration remains unknown. In this study, we implanted SHED in a porcine dental pulp regeneration model to evaluate the regenerative effect and identify whether SHED promoted angiogenesis in regenerated dental pulp. Firstly we verified that xenogenous SHED had the ability to regenerated pulp tissue of host in vivo. Then we found the vasculature in regenerated pulp originated from implanted SHED. In addition, stem cells were isolated from regenerated dental pulp, which exhibited good multi-differentiation properties and promoted angiogenesis in pulp regeneration process and these results demonstrated that SHED promoted angiogenesis in stem cell-mediated dental pulp regeneration.

Introduction This report describes the treatment of an immature mandibular molar by combining vital pulp therapy (VPT) and regenerative endodontic procedures (REPs). It details the use of REP to regain functionality and continued root development of an immature root with pulp necrosis and VPT for an immature root containing vital pulpal tissues. Methods An 8-year old male presented for evaluation of a mandibular first right molar with mild buccal swelling and a nontraceable sinus tract. He recently had received a restoration. After intraoral and radiographic examination, a diagnosis of pulp necrosis and chronic apical abscess was made. After access, pulp necrosis was confirmed in the distal root; however, vital pulp tissues were present in the mesial canals. It was decided on pulpotomy (VPT) in the mesial and REP in the distal root. At the initial visit, pulpotomy was completed in the mesial root, and REP was initiated in the distal root. Three weeks later, the patient was asymptomatic and the sinus tract absent. REP was completed in the distal root, and the tooth was restored. Results At the 6-, 12-, and 18-month follow-up, the patient presented without symptoms, and the tooth responded positively to pulp sensibility tests. Radiographic examinations showed resolution of the apical radiolucency and completed root development. Conclusions Combined treatment using both VPT and REP for immature molars with different pulpal status in individual roots may be a preferable treatment option because preservation of vital pulp tissues and regeneration of new vital tissues allow for continued root development and functionality.

Mineralized enamel and dentin provide protection to the dental pulp, which is vital tissue rich with cells, vasculature, and nerves in the inner tooth. Dental caries left untreated threaten exposure of the dental pulp, providing facile access for bacteria to cause severe infection both in the pulp and systemically. Dental materials which stimulate the formation of a protective dentin bridge after insult are necessary to seal the pulp chamber in an effort to maintain natural dentition and prevent pulpal infection. Dental materials to date including calcium hydroxide paste, mineral trioxide aggregate, and glass ionomer resin, are used with mixed results. Herein we exploited the cell-cell communicative properties of exosomes, extracellular vesicles derived from both mineralizing primary human dental pulp stem cells (hDPSCs) and an immortalized murine odontoblast cell line (MDPC-23), to catalyze the formation of a reactionary dentin bridge by recruiting endogenous stem cells of the dental pulp, through an easy-to-handle delivery vehicle which allows for their therapeutic controlled delivery at the pulp interface. Exosomes derived from both hDPSCs and MDPCs upregulated odontogenic gene expression and increased mineralization in vitro. We designed an amphiphilic synthetic polymeric vehicle from a triblock copolymer which encapsulates exosomes by polymeric self-assembly and maintains their biologic integrity throughout release up to 8–12 weeks. The controlled release of odontogenic exosomes resulted in a reparative dentin bridge formation, superior to glass-ionomer cement alone in vivo, in a rat molar pulpotomy model after six weeks. We have developed a platform for the encapsulation and controlled, tunable release of cell-derived exosomes, which maintains their advantageous physiologic properties reflective of the donor cells. This platform is used to modulate downstream recipient cells towards a designed dentinogenic trajectory in vitro and in vivo. Additionally, we have demonstrated the utility of an immortalized cell line to produce a high yield of exosomes with cross-species efficacy.

Introduction Factors that influence clinical outcomes for regenerative endodontic procedures (REPs) are unknown. This retrospective study aimed to assess tooth healing, root development, pulp vitality, and esthetics post-REPs and categorize them into clinician- and patient-centered outcomes. Furthermore, this study identified significant predictors affecting such outcomes. Methods Immature permanent teeth diagnosed with pulp necrosis treated with REPs between 2008 and 2018 with a minimum of 1-year follow-up were included. Outcomes included success and survival rates, changes in root development using 2-dimensional radiographic root area (RRA) and 3-dimensional measurements, pulp vitality, and tooth discoloration. Predictor variables of success included age, sex, etiology of pulp necrosis (PN), type of medicament, sodium hypochlorite (NaOCl) concentration, type of biomaterial used over the blood clot, and preoperative apical diagnosis. Statistical analyses included Cox proportional hazard analyses and generalized regression models. Results Fifty-one teeth with an average of 2.1 years of follow-up satisfied the criteria. The survival rate was 92%. The success rate was 84.3% with age, etiology of PN, type of medicament, and NaOCl concentration being significant predictors of failure. Root development occurred in 91.4% of cases with age, sex, etiology of PN, type of medicament, NaOCl concentration, and apical diagnosis being significant predictors for RRA change. Positive pulp sensibility responses were associated with greater RRA change, and, finally, the type of biomaterial was a significant predictor for tooth discoloration after treatment. Conclusions : REPs provide a high survival rate. Patient and clinical factors may affect outcomes, and this knowledge may help to define the criteria for optimal treatment planning of REPs.

Introduction This study aimed to examine the process of reinnervation during coronal pulp tissue regeneration in a rat model in which rat bone marrow mesenchymal stem cells were implanted in pulpotomized molars. Methods The maxillary first molars of Wistar rats were pulpotomized, and preformed biodegradable porous poly L-lactic acid scaffolds and hydrogel carrying rat bone marrow mesenchymal stem cells were implanted in the pulp chamber. After 3, 7, and 14 days, the implanted teeth were processed for histologic analysis; immunoperoxidase staining for protein gene product 9.5 (a general neuronal marker), calcitonin gene-related peptide (CGRP), or substance P (SP); and real-time polymerase chain reaction for nerve growth factor (NGF) and growth-associated protein 43 (GAP-43) messenger RNA (mRNA) expression. Results Histologic analysis of the implanted region revealed sparse cellular distribution at 3 days, pulplike tissue with a thin dentin bridge–like structure at 7 days, and dentin bridge–like mineralized tissue formation and resorption of most scaffolds at 14 days. Protein gene product 9.5 and CGRP-immunoreactive nerve fibers showed the lowest density at 3 days and significantly increased until 14 days when the CGRP-immunoreactive fibers reached normal levels. SP-immunoreactive nerve fibers showed the highest density at 7 days and decreased to normal levels at 14 days. NGF mRNA increased with time, whereas GAP-43 mRNA levels peaked at 3 days and subsequently dropped until 14 days. Conclusions Regeneration/remodeling of SP-immunoreactive and CGRP-immunoreactive nerve fibers with increased mRNA expression of NGF and GAP-43 occurred in a rat model of coronal pulp tissue engineering with bone marrow mesenchymal stem cells.

Introduction This study assessed the cleaning, shaping, and disinfection abilities of 2 instrumentation systems in molar root canals using a novel correlative analytical approach. Methods The root canals from extracted mandibular and maxillary molars with apical periodontitis were pair matched according to anatomic similarities as determined by micro–computed tomographic analysis and prepared with either XP-endo Shaper (FKG Dentaire, La Chaux-de-Fonds, Switzerland) (n = 16) or Reciproc Blue (VDW, Munich, Germany) (n = 16) instruments and 2.5% sodium hypochlorite irrigation. Pre- and postpreparation micro–computed tomographic scans were used to identify and calculate the unprepared surface areas (shaping), which were histobacteriologically evaluated for the presence of residual bacteria (disinfection) and pulp tissue remnants (cleaning) in each canal third. Results Unprepared canal surface areas for XP-endo Shaper and Reciproc Blue in the full canal length were approximately 26% and 19% (P .05). Preparation with Reciproc Blue resulted in 37.5% canals free of bacteria in all sections examined and 56% in the apical sections only. XP-endo Shaper resulted in 44% canals free of bacteria in all sections, and 56% in the apical part of the canal only. Pulp tissue remnants were not observed in 31% (all canal sections) and 50% (apical canal sections) of specimens from both instrument systems. No significant differences were observed between instruments when comparing the amount of pulp tissue remnants and the number of cases negative for bacteria and tissue remnants (P > .05). Conclusions Although the Reciproc Blue instrument had superior shaping ability in comparison with XP-endo Shaper, both systems performed similarly in cleaning and disinfecting root canals. Irregular canals and difficult-to-reach areas were not thoroughly cleaned and disinfected by any of the tested systems.

Introduction The aim of this in vivo study was to investigate the microbial profile as well as the levels of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) at different phases of endodontic treatment in teeth with vital pulp and associated periodontal disease. Methods Ten patients were selected for this clinical study. Samples were taken from periodontal pockets (PPs) and root canals (RCs) using sterile paper points before and after chemomechanical preparation and after intracanal medication. For microbiological analysis, nested polymerase chain reaction and checkerboard DNA-DNA hybridization were used. Levels of LPS and LTA were assessed using limulus amebocyte lysate and enzyme-linked immunosorbent assays, respectively. Data were statistically analyzed at a significance level of 5%. Results Bacterial DNA from 17 of the 17 species investigated was detected in samples of PPs, whereas 6 of the 17 species were not present in the initial samples of RCs using nested polymerase chain reaction. In the initial samples, 38 of 40 probes were detected in PPs, whereas 12 of 40 probes were detected in RCs using checkerboard DNA-DNA hybridization. Overall, endodontic procedures were efficient in modifying the microbiota of PPs and RCs. Levels of LPS and LTA were reduced after the endodontic procedures, although higher concentrations of both had been found in PPs compared with RCs. Conclusions The microbiota of PPs and RCs in teeth with vital pulp and associated periodontal disease is polymicrobial, with the presence of gram-negative, gram-positive, facultative, and strict anaerobes. Chemomechanical preparation and calcium hydroxide–based intracanal medication allowed the reduction of infectious content in both sites.

Introduction Cone-beam computed tomographic (CBCT) imaging is useful in detecting apical periodontitis, which is often missed in periapical (PA) radiographs. This study aimed to identify preoperative predictors correlated with the presence of apical periodontitis visible only in CBCT images and to investigate the important characteristics of such lesions. Methods In total, 332 consecutive patients with both PA radiographs and CBCT images were enrolled in this study. The patients’ clinical charts were reviewed retrospectively to collect information regarding their symptoms and diagnoses. Periapical lesions were assessed using a modified CBCT PA index by 2 endodontists. Patient-related factors (age, sex, and symptoms) and tooth-related factors (tooth type, location, pulp status, and pulpal diagnosis) were assessed to determine their relationships with the presence of apical periodontitis visible only in CBCT images. Results Apical periodontitis was detected in 24.6% and 35.5% of untreated teeth by PA radiographs and CBCT images, respectively. In a multivariate logistic regression analysis, pulp necrosis was significantly correlated with the presence of apical periodontitis visible only in CBCT images (odds ratio = 5.401; 95% confidence interval, 1.911–15.265; P = .001); the involvement of molars showed borderline nonsignificant correlation (odds ratio = 2.843; 95% confidence interval, 0.990–8.164; P = .052). Lesion sizes smaller than 2 mm in diameter and the involvement of molars were significant factors of lesions visible only in CBCT images (P Conclusions Pulp necrosis was a preoperative predictor of apical periodontitis visible only in CBCT images. This research could provide a proper indication for CBCT imaging at diagnostic stages.

Introduction The present study quantitatively assessed tissue regeneration after regenerative endodontic procedures (REPs) with 2 different apical preparation sizes in mature teeth using magnetic resonance imaging (MRI). Methods Eighteen maxillary anterior mature necrotic teeth with periapical lesions were selected for the study. The teeth were randomly allocated into 2 groups. Canal preparation was performed using Protaper Next files (Dentsply Sirona, York, PA) until size X3 and X5 in the test and control groups, respectively. REPs were performed, and Biodentine (Septodont, Saint-Maur-des-Fosses, France) was used as the cervical plug material. In both groups, MRI was used to measure the signal intensity (SI) of the regenerated tissue at 3, 6, and 12 months at both the middle and the apical thirds of the canal. The SI between the normal contralateral teeth and each successive interval was compared. Clinical examination, sensibility tests, and digital periapical radiographs were also performed at successive time intervals. Statistical analysis was performed using the Student t test and Cochran test. The level of significance was set at P ≤ .05. Results All 18 teeth were symptom free with healing of the periapical lesions. Regarding the SI measurements, there was no statistically significant difference between the SI of the normal contralateral teeth and that of the regenerated tissues in the treated teeth after a 12-month follow-up. In both groups, more than 60% of the cases regained pulp sensibility after 12 months. Conclusions Vital pulplike tissue could be successfully regenerated in mature teeth using REPs, which was not significantly affected by the size of the apical diameter. MRI could successfully assess this tissue in a quantitative, noninvasive manner.

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

Background Dental caries continue to represent a major problem which, if left untreated, will cause irreversible pulpitis. Root canal treatment constitutes one potential treatment intended to preserve teeth afflicted with irreversible pulpitis. During root canal treatment, pain or swelling, referred to as flare-ups, can occur at any point in the process. Aim To analyze the molecular aspect of the phenomenon of flare-up in vital dental pulp tissue following mechanical and bacterial trauma (extirpation and lipopolysaccharide [LPS] induction respectively) through a neurological approach, based on the expression of NaV-1.7 in neuron cells, and HSP-70, TNF-α in macrophage cells. Method This laboratory experimental study was conducted using 15 Spraque Dawley rats as subjects which were divided into three groups of five subjects: a control group, a pulp tissue extirpation group and an LPS induction followed by extirpation of pulp tissue group. Test samples were collected from the apical field of the mandibular incisor and subsequently examined using immunohistochemical methods. Results There were significant differences in NaV1.7, HSP70 and TNFα expression between the treatment groups. While a marked increase in the expression of HSP70 occurred, both Nav1.7, and TNFα expression decreased significantly. Conclusion Extirpating the dental pulp tissue will induce a more pronounced flare-up response from the molecules of the pulp tissue in vital teeth than those in inflamed vital pulp tissue.

Inhibiting the activity of α-glucosidase and glycosylation of protein is an important way to treat diabetes mellitus and its complications. In this study, we investigated the anti-α-glucosidase activity, anti-glycation potential and structure of proanthocyanidins from fruit pulp of Clausena lansium (Lour.) Skeels. C. lansium fruit pulp proanthocyanidins showed a remarkable inhibition against α-glucosidase activity with IC50 vaule of 0.26 ± 0.01 μg/mL in a competitive manner, and quenched the fluorescence of α-glucosidase by forming proanthocyanidin-α-glucosidase complex. Furthermore, compared to positive agent aminoguanidine (AG), the proanthocyanidins were the more significant inhibitors of non-enzymatic glycation by strongly inhibiting the formation of α-dicarbonyl compounds and advanced glycation end products. In addition, the structure of the proanthocyanidins was characterized in detail. These compounds were mainly composed of prodelphinidins, and their gallates. The main extender units, gallocatechin epigallocatechin and their gallates, were critical factor of the strong anti-α-glucosidase and anti-glycation activity. Therefore, this study authenticated a efficient α-glucosidase inhibitors and antiglycation agents, which would contribute to the development of anti-diabetic drug.

OBJECTIVE: To evaluate, by means of an ex-vivo human tooth-culture model and in-vivo minipig animal study, the pulpal inflammatory reaction and reparative dentin-formation capacity of an injectable phosphopullulan-based calcium-silicate cement (GC, Tokyo, Japan) upon pulp capping, this in comparison with the commercial reference material Biodentine (Septodont). METHODS: For the ex-vivo tooth model, 9 freshly-extracted teeth from 3 different patients were pulp-capped with the experimental biomaterial (n = 3), Biodentine (n = 3) or left uncapped (control; n = 3). The teeth were kept in fresh culture medium for 4 weeks and, upon fixation three-dimensional Micro-CT and histology were performed. For the in-vivo animal study, 40 teeth from 3 minipigs were exposed and pulp capped with the experimental biomaterial containing phosphopullulan (n = 24) or Biodentine (n = 16) for 7 or 70 days. The inflammatory reaction and the tissue-regenerative potential was qualitatively and semi-quantitatively characterized using three-dimensional micro-CT and histology. RESULTS: Ex vivo, the treatment with the experimental phosphopullulan-based calcium-silicate cement and Biodentine stimulated the formation of fibrous tissue and mineralized foci. In vivo, early inflammatory reaction and regeneration of the pulp-tissue interface was promoted by both bioceramic materials after 7 and 70 days, respectively. SIGNIFICANCE: Our findings bring new insights into calcium-silicate-mediated dental pulp repair and regeneration. The novel ready-to-use and self-adhering functionalized calcium-silicate cement revealed effective pulpal repair potential. ispartof: DENTAL MATERIALS vol:36 issue:4 pages:512-526 ispartof: location:England status: published

Pulpotomy in mature permanent cariously exposed teeth preserves the remaining pulp tissues, but long-term outcomes of the pulp and the restoration are unknown. This prospective study examined the immediate and long-term status of the pulp and the restored tooth and identified potential predictors of early and late failures in teeth that were asymptomatic or experiencing only mild symptoms at the time of treatment.Pulpotomy was performed using the aseptic technique and a tricalcium silicate cement under local anesthesia. Teeth were assessed for up to 5 years for pulpal and apical signs and symptoms, restorative marginal integrity, and periodontal health.Fifty-two patients (61 teeth) with a median age of 40 years (range, 21-75 years) were included in this study; 17 (32.7%) men and 35 (67.3%) women were treated and reviewed. Overall pulp survival was 90.2% (95% confidence interval, 79.8%-96.3%); 6 teeth developed irreversible pulpitis or pulp necrosis when the restoration was intact. Preoperative pain was a potential predictor (P.05) for early failure. Eleven late failures occurred between 2 and 4 years: 1 tooth with intact coronal restoration had pulp necrosis and asymptomatic apical periodontitis, 4 had recurrent caries resulting in asymptomatic apical periodontitis, 4 remained vital and only needed new restorations, 1 was unrestorable, and 1 was extracted for periodontal reasons. The type of definitive restoration was a potential predictor for late failure (P .05).Carious pulp exposures in asymptomatic mature permanent teeth can be predictably managed by pulpotomy using a tricalcium silicate cement. Short-term failures were few and managed by pulpectomy. Appropriate coronal restoration is critical to long-term success.

Summary The teeth are considered as a reliable indicator of age and provide several parameters for age estimation. Age estimation from dental radiographs is a non-destructive and straightforward method to obtain information. This preliminary study aimed to establish a relationship between chronological age and the tooth/pulp area ratio in a central Indian population. The digital dental X-ray- OPGs of 46 randomly selected consenting subjects belonging to the age group 18 to 60 years were examined. The tooth area and pulp area of upper maxillary right permanent canine were calculated. A Graph was also plotted on the scattered points to get a linear trend line and equation of the relationship between chronological age and tooth/pulp area ratio. Statistical analysis shows a significant strong positive correlation (R2= 0.99) between age and tooth /pulp area ratio. Linear Regression equation was derived for estimation of age, i.e., y = 6.6554x - 22.578 (where y is the estimated age and x is the tooth-pulp area ratio). The estimated age was accurate up to ± 2 years of the actual age. The result of this preliminary study shows that the tooth/pulp area ratio of the canine may serve as a reliable tool for estimation of age.

Diabetes is a common disease that may have some influence on sensory nerves. The aim of this study was to evaluate dental pulp responses to 2 pulp sensibility tests (ie, cold and electric) in patients with type 2 diabetes compared with healthy individuals.Three hundred twenty-two premolar teeth in 51 patients who had type 2 diabetes and 347 premolar teeth in 53 individuals with no medical conditions were investigated. The patients with type 2 diabetes were unified and had fasting plasma glucose300, hemoglobin A1C10, less than a 10-year history of diabetes mellitus, and no history of hypertension. Electric and cold pulp sensibility tests were performed for all teeth. The cold test results were recorded by the Heft-Parker visual analog scale, and the electric pulp test results were recorded based on the pulp tester's grade that evoked a response.There was no statistically significant difference between upper and lower premolar teeth in healthy individuals compared with the patients with diabetes in response to the cold and electric pulp tests (P.05). In the patients with diabetes, the response of their upper premolars to the cold test was significantly reduced in diabetic patients45 years of age (β = -1.15, P = .013). However, there was no significant correlation between the cold test and age in the lower premolars of both diabetic and nondiabetic participants (P.05). There was also no significant correlation between the need for a higher number of the electric pulp test current to evoke a response in maxillary and mandibular premolars of the patients with diabetes and nondiabetic participants with age (P.05).There was a significant correlation between the reduction of maxillary premolar teeth responses to the cold test in diabetes patients45 years of age.