Clinical influencing factors of vital pulp therapy on pulpitis permanent teeth with 2 calcium silicate-based materials: A randomized clinical trial.

BACKGROUND: Compared with traditional root canal therapy (RCT), vital pulp therapy (VPT) is a personalized and minimally invasive method for the treatment of pulpitis caused by dental caries. However, there are still no clear guidelines for VPT because high-quality randomized clinical trials are scarce. This prospective cohort study evaluated the clinical efficacy of VPT with the light-curable calcium silicate-based material TheraCal LC (TH) and bioceramic material iRoot BP Plus (BP) in reversible and irreversible pulpitis permanent teeth with carious exposures. METHODS: 115 teeth with reversible or irreversible pulpitis caused by deep care were randomly divided into 2 groups. TheraCal LC and iRoot BP Plus were used for the pulp capping. Direct pulp capping (DPC), partial pulpotomy (PP) and full pulpotomy (FP) were performed based on observation of the exposed pulp. Postoperative discomforts were enquired and recorded via follow-up phone calls. Clinical and radiographic evaluations were performed 3, 6, and 12 months postoperatively. RESULTS: The overall clinical success rate in the first year was 90.4% (47/52) in both groups. The TH group required less operating time, showed lower levels of pain, and had shorter pain duration post-operative (P < .001). According to the binary logistic regression model, preoperative pain duration was significantly correlated with the prognosis of VPT (P = .011). CONCLUSION: VPT with TheraCal LC and iRoot BP Plus in pulpitis permanent carious teeth both achieved good clinical outcomes, and TheraCal LC can be easily operated for clinical use. Preoperative pain duration of the affected tooth might have a significant correlation with the prognosis of VPT.

Manganese Dioxide-Based Nanomaterials for Medical Applications.

Manganese dioxide (MnO2) nanomaterials can react with trace hydrogen peroxide (H2O2) to produce paramagnetic manganese (Mn2+) and oxygen (O2), which can be used for magnetic resonance imaging and alleviate the hypoxic environment of tumors, respectively. MnO2 nanomaterials also can oxidize glutathione (GSH) to produce oxidized glutathione (GSSG) to break the balance of intracellular redox reactions. As a consequence of the sensitivity of the tumor microenvironment to MnO2-based nanomaterials, these materials can be used as multifunctional diagnostic and therapeutic platforms for tumor imaging and treatment. Importantly, when MnO2 nanomaterials are implanted along with other therapeutics, synergetic tumor therapy can be achieved. In addition to tumor treatment, MnO2-based nanomaterials display promising prospects for tissue repair, organ protection, and the treatment of other diseases. Herein, we provide a thorough review of recent progress in the use of MnO2-based nanomaterials for biomedical applications, which may be helpful for the design and clinical translation of next-generation MnO2 nanomaterials.

Novel cryotherapy technique for pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis- a randomized controlled trial.

OBJECTIVES: To assess the effect of cryotherapy on haemostasis, post-operative pain, and the outcome of full pulpotomy performed in mature permanent teeth with symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study included sixty mature permanent mandibular molar teeth with symptomatic irreversible pulpitis and no periapical rarefaction. After coronal pulp tissue amputation, teeth were randomly allocated to one of two groups (n = 30 each). In group I (conventional pulpotomy), a sterile cotton pellet moistened with 2.5% NaOCl was used for haemostasis. In group II (cryotherapy), the pulp chamber was continuously lavaged with 2.50C normal saline solution for haemostasis using an indigenous portable cryotherapy irrigation unit. Following haemostasis, the pulp was capped with mineral trioxide aggregate and the tooth was restored with resin composite. The time taken to achieve haemostasis was recorded. Preoperative and 24, 48 and 72 h postoperative pain was measured using the Numerical Rating Scale. The pulpotomy outcome was assessed at the 12-month follow-up. Data were analyzed using Fischer's exact test, two-sample t-test, two-sample Wilcoxon rank-sum test, Friedman Test, and Wilcoxon Signed Rank Test. RESULTS: The cryotherapy group achieved haemostasis in less time (p < 0.05). There was a significant pain reduction at 24 and 48 h in the cryotherapy group when compared with the conventional pulpotomy group (P < 0.005). The overall success rate of pulpotomy after 12 months was 88% (n = 22) in both study groups(p < 0.05). CONCLUSIONS: Cryotherapy application reduces postoperative pain and has no adverse effect on the outcome of pulpotomy in permanent teeth with symptomatic irreversible pulpitis. CLINICAL RELEVANCE: The cryotherapy can be incorporated in pulpotomy protocol as an adjunct to minimize post-operative pain.

Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial.

BACKGROUND: Recent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19. METHODS: We performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load. RESULTS: Of a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447). CONCLUSIONS: In asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings.

Comparative Evaluation of Push-out Bond Strength of Conventional Mineral Trioxide Aggregate, Biodentine, and Two Novel Antibacterial-enhanced Mineral Trioxide Aggregates.

AIM: To evaluate the push-out bond strength of two newly modified mineral trioxide aggregates (MTAs) with conventional MTA and biodentine. MATERIALS AND METHODS: Material preparation: Two commercially available bioactive bioceramics: Group I: Mineral trioxide aggregate; Group II: Biodentine; and two newly formulated modified MTAs: Group III: Doxycycline incorporated MTA formulation; Group IV: Metronidazole incorporated MTA formulation was used in the present study. All the test materials were then carried using a plastic instrument to the desired experimental design. Teeth sample preparation: A total of 120 teeth samples were collected and divided into four groups of test materials with 30 teeth samples per group. Single-rooted permanent teeth, that is, incisors were collected and stored in saline until the study was performed. Sectioning of the teeth into 2.0 ± 0.05-mm thick slices was performed perpendicular to the long axis of the tooth. The canal space was instrumented using Gates Glidden burs to achieve a diameter of 1.5 mm. All four prepared materials were mixed and placed in the lumen of the slices and placed in an incubator at 37°C for 72 hours. Push-out test and bond failure pattern evaluation: The push-out test was performed using a universal testing machine. The slices were examined under a scanning electron microscope (SEM) at 40× magnification to determine the nature of bond failure. All the collected data were recorded and statistically analyzed. RESULTS: The mean push-out bond strength was found to be the highest for group II (37.38 ± 1.94 MPa) followed by group III (28.04 ± 2.22 MPa) and group IV (27.83 ± 1.34 MPa). The lowest mean push-out bond strength was noticed with group I (22.89 ± 2.49 MPa). This difference was found to be statistically significant (p = 0.000). Group I samples had the predominantly adhesive type of failure (86.4%), while group II samples showed the cohesive type of failure (94.2%). Both the modified MTAs (groups III and IV) primarily showed mixed types of failures. CONCLUSION: Both the antibacterial-enhanced MTAs had better pushout bond strength compared to conventional MTA but did not outperform biodentine. Hence, it could serve as a substitute for conventional MTA due to its augmented physical properties. CLINICAL SIGNIFICANCE: Carious pulp exposure and nonvital open apices pose a critical challenge to pediatric dental practitioners. In such circumstances, maintaining the vitality of pulp and faster healing would help in a better prognosis. Novel MTAs without any cytotoxic components, and enhanced antibacterial contents with augmented physical properties can help in treating such clinical conditions. How to cite this article: Merlin ARS, Ravindran V, Jeevanandan G, et al. Comparative Evaluation of Push-out Bond Strength of Conventional Mineral Trioxide Aggregate, Biodentine, and Two Novel Antibacterial-enhanced Mineral Trioxide Aggregates. J Contemp Dent Pract 2024;25(2):168-173.

Failed Regenerative Endodontic Case Treated by Modified Aspiration-irrigation Technique and Apexification.

AIM: This report addresses the management of a large persistent discharging lesion in an 11-year-old boy. The report describes the use of aspiration-irrigation technique for the management of immature necrotic tooth with persistent discharge after a failed regenerative procedure. BACKGROUND: Regenerative endodontics aim to provide an increase in root canal width, length, and in apical closure. Alternative procedures, such as apexification, should be attempted when regeneration fails. If the canal cannot be dried to persistent discharge, the aspiration-irrigation technique can be used. The technique relies on using aspiration along with irrigation to remove pus from the periapical area. CASE DESCRIPTION: This is a case for an 11-year-old patient who had trauma to tooth #11, which resulted in the complicated crown fracture. He had an emergency management that included pulpectomy and intracanal medication at another clinic. Two years later, the patient was presented to our clinic. Upon examination, the diagnosis was previously initiated therapy with asymptomatic apical periodontitis in immature tooth #11. Regeneration was attempted first but failed. The mineral trioxide aggregate (MTA) plug was removed, and the canal had persistent pus discharge. The canal was filled with intracanal medication, and then 2 weeks later, the canal was filled with triple antibiotic paste (TAP). Next visit, and due to continuous discharge, tooth #11 was treated conservatively with an intracanal aspiration-irrigation technique. An IrriFlex needle attached to a high-volume suction was used to aspirate the cystic fluid. Mineral trioxide aggregate plug apexification was performed in a later visit and the tooth was restored. CONCLUSION: During the 3-month and 16-month follow-up, there was resolution of the symptoms, a decrease in the periapical lesion size, and soft tissues appeared within normal limits. CLINICAL SIGNIFICANCE: Regenerative procedures are a good option for immature necrotic teeth. These procedures may fail due to persistent pus discharge from the root canals. The aspiration-irrigation technique is a good treatment option in cases of consciously discharging canals. How to cite this article: Alsofi L, Almarzouki S. Failed Regenerative Endodontic Case Treated by Modified Aspiration-irrigation Technique and Apexification. J Contemp Dent Pract 2024;25(1):92-97.

Hard tissue formation in pulpotomized primary teeth in dogs with nanomaterials MCM-48 and MCM-48/hydroxyapatite: an in vivo animal study.

BACKGROUND: This animal study sought to evaluate two novel nanomaterials for pulpotomy of primary teeth and assess the short-term pulpal response and hard tissue formation in dogs. The results were compared with mineral trioxide aggregate (MTA). METHODS: This in vivo animal study on dogs evaluated 48 primary premolar teeth of 4 mongrel female dogs the age of 6-8 weeks, randomly divided into four groups (n = 12). The teeth underwent complete pulpotomy under general anesthesia. The pulp tissue was capped with MCM-48, MCM-48/Hydroxyapatite (HA), MTA (positive control), and gutta-percha (negative control), and the teeth were restored with intermediate restorative material (IRM) paste and amalgam. After 4-6 weeks, the teeth were extracted and histologically analyzed to assess the pulpal response to the pulpotomy agent. RESULTS: The data were analyzed using the Kruskal‒Wallis, Fisher's exact, Spearman's, and Mann‒Whitney tests. The four groups were not significantly different regarding the severity of inflammation (P = 0.53), extent of inflammation (P = 0.72), necrosis (P = 0.361), severity of edema (P = 0.52), extent of edema (P = 0.06), or connective tissue formation (P = 0.064). A significant correlation was noted between the severity and extent of inflammation (r = 0.954, P < 0.001). The four groups were significantly different regarding the frequency of bone formation (P = 0.012), extent of connective tissue formation (P = 0.047), severity of congestion (P = 0.02), and extent of congestion (P = 0.01). No bone formation was noted in the gutta-percha group. The type of newly formed bone was not significantly different among the three experimental groups (P = 0.320). CONCLUSION: MCM-48 and MCM-48/HA are bioactive nanomaterials that may serve as alternatives for pulpotomy of primary teeth due to their ability to induce hard tissue formation. The MCM-48 and MCM-48/HA mesoporous silica nanomaterials have the potential to induce osteogenesis and tertiary (reparative) dentin formation.

Reprint of: The Effect of Mineral Trioxide Aggregate Obturation Levels on the Outcome of Endodontic Retreatment: An Observational Study.

INTRODUCTION: No clinical studies have examined the effect of mineral trioxide aggregate (MTA) obturation levels on the outcome of endodontic retreatment. This retrospective study examined treatment outcomes in three cohorts that compared overfilling, flush filling, and underfilling after orthograde retreatment using MTA. METHODS: Two hundred fifty patients with 264 teeth diagnosed with previously treated root canals and apical periodontitis retreated in a private endodontic practice were included. All teeth received MTA obturation and the extent of the final filling level was measured in relation to the major apical foramen. After 6-month follow-ups, all nonhealing cases were treated surgically. After 24- to 72-month reviews, the effect of preoperative lesion size and the degree of MTA obturation level were assessed. Multiple linear regression and time-to-event analysis using Stata 17 software (StataCorp LLC, College Station, TX) were used to evaluate the data. RESULTS: Within the three cohorts, 99 out of 108 overfilled teeth (91.7%), 90 out of 103 flush fills (87.4%), and 10 out of 53 underfilled teeth (18.9%) healed and were successfully retreated without surgery at 48-months. When surgical outcomes were included, the combined healed proportion was 93.2%. Preoperative lesion size was found to be an important predictor for retreatment nonhealing. A 1-mm increase in lesion size at baseline resulted in an estimated 11% (95% CI 1.04, 1.18)-38% (95% CI 1.22, 1.58) increase in the risk of surgery. Compared to overfilling and flush filling, underfilling was associated with an approximately three-fold increase in requiring surgery and characterized by delayed healing. CONCLUSION: MTA obturation is a viable retreatment option for teeth with nonhealing endodontic treatment. MTA overfills or flush fillings do not adversely affect healing outcomes. However, MTA underfilling increases the chances for nonhealing and surgical intervention.

Platelet rich fibrin and MTA in the treatment of teeth with open apices.

BACKGROUND: The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical lesions and open apices. METHODS: Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance. RESULTS: All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments. CONCLUSIONS: PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.

Gaillardin exerts potent antileukemic effects on HL-60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment.

The use of all-trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard-risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high-risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus-christi-derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high-risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL-60 cells as a single or combined-form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL-60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL-60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL-60 cells and this study provides new insight into treating APL patients, especially in the high-risk subgroup.

One-year radiographic and clinical performance of bioactive materials in primary molar pulpotomy: A randomized controlled trial.

OBJECTIVES: Mineral Trioxide Aggregate (MTA) is considered the gold standard material for pulpotomy procedures. However, some drawbacks such as poor handling and long setting time are challenging when it is used as pulpotomy dressing in primary molars in children. Hence, the purpose of this study was to compare the radiographic and clinical performance of a premixed, fast setting bioceramic root repair material (BC RRM-F) with MTA in vital pulpotomy procedures of primary molars, with or without the added seal of a stainless steel crown (SSC). METHODS: In this double blinded, four-arm, parallel group randomized contolled trial (RCT), 64 primary molars were randomly allocated to one of the four treatment groups: MTA (PDTM MTA WHITE)+SSC, MTA+GI (bulk fill glass ionomer with glass hybrid technology GC EQUIA Forte® HT), BC RRM-F+GI and BC RRM-F+SCC. All molars were evaluated clinically and radiographically according to the modified Zurn and Seale criteria at 1, 3, 6, and 12 months follow up. Multivariate cox regression models and Kaplan-Meier curves were used for survival analysis. RESULTS: There was no statistically significant difference between the success of both pulp capping materials used. Overall survival analysis showed that using GI instead of SCC as a final restorative material was significantly associated with increased risk of failure. CONCLUSIONS: TotalFill® BC RRM™ Fast Set Putty can be used as an alternative to MTA in primary molar pulpotomy. Regardless of the pulp capping material, one year survival of pulpotomized primary molars restored with SSC is higher compared to those restored with GC EQUIA Forte® HT. CLINICAL SIGNIFICANCE: Clinicians' preference and cost effectiveness may justify the use of either material in primary molar pulpotomy. Parents insisting on tooth-colored restorations for their children's pulpotomized teeth cannot be told that the expectation for success is the same as those restored with SSC, even if calcium silicate-based pulp capping materials are used.

Biodentine as a pulpotomy medicament for primary molars: a retrospective chart review.

This retrospective chart review study investigates the long-term clinical outcome of Biodentine® (Tricalcium silicate) as a medicament for pulpotomy in primary molars. Data in this retrospective study was collected from the dental records of all patients that had at least one primary molar receive pulpotomy treatment (CDT code: D3221) between 01 July 2012 and 01 July 2015. This data includes child's age, medical history, dental history, dental radiographs, pulpotomy procedure details and follow-up clinical notes. Kaplan-Meier Estimate was used to measure the fraction of successful pulpotomy procedures for up to 24 months. A total of 1758 pulpotomy procedures were performed on 1032 patients in our institute in the three-year period and 21.4% of them (N = 376) had follow-up dental records that qualified for the study. Eleven teeth out of 376 teeth were excluded from the statistical analysis due to loss of/broken stainless steel crowns (3.1%). Seventeen pulpotomy failures were identified out of the remaining 365 procedures. The survival probablity of using Biodentine® as a pulpotomy medicament is 96.3% for 18-month follow-up and 95.4% for 24-month follow-up. Biodentine®, a tricalcium silicate formulation, used as a pulpotomy medicament demonstrates a high clinical success rate (95.4%) over a 24-month peroid in primary molars.

An Immunocompetent Hafnium Oxide-Based STING Nanoagonist for Cancer Radio-immunotherapy.

cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core-shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO2) core and the manganese oxide (MnO2) shell. HfO2-mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO2 sustainably releases Mn2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy.

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain.

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of reactive oxygen species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves. To address the pathological issues of disc degeneration and discogenic pain, we developed MnO2@TMNP, a nanomaterial that encapsulated MnO2 nanoparticles with a TrkA-overexpressed macrophage cell membrane (TMNP). Consequently, this engineered nanomaterial showed high efficiency in binding various inflammatory factors and nerve growth factors, which inhibited inflammation-induced NPC apoptosis, matrix degradation, and nerve ingrowth. Furthermore, the macrophage cell membrane provided specific targeting to macrophages for the delivery of MnO2 nanoparticles. MnO2 nanoparticles in macrophages effectively scavenged intracellular ROS and prevented M1 polarization. Supportively, we found that MnO2@TMNP prevented disc inflammation and promoted matrix regeneration, leading to downregulated disc degenerative grades in the rat injured disc model. Both mechanical and thermal hyperalgesia were alleviated by MnO2@TMNP, which was attributed to the reduced calcitonin gene-related peptide (CGRP) and substance P expression in the dorsal root ganglion and the downregulated Glial Fibrillary Acidic Protein (GFAP) and Fos Proto-Oncogene (c-FOS) signaling in the spinal cord. We confirmed that the MnO2@TMNP nanomaterial alleviated the inflammatory immune microenvironment of intervertebral discs and the progression of disc degeneration, resulting in relieved discogenic pain.

Histological evaluation of the regenerative potential of a novel photocrosslinkable gelatin-treated dentin matrix hydrogel in direct pulp capping: an animal study.

BACKGROUND: To assess histologically the success of the pulp capping approach performed in traumatically exposed dogs' teeth using a novel injectable gelatin-treated dentin matrix light cured hydrogel (LCG-TDM) compared with LCG, MTA and TheraCal LC. METHODS: Sixty-four dogs' teeth were divided into two groups (each including 32 teeth) based on the post-treatment evaluation period: group I: 2 weeks and group II: 8 weeks. Each group was further subdivided according to the pulp capping material into four subgroups (n = 8), with subgroup A (light-cured gelatin hydrogel) as the control subgroup, subgroup B (LCG-TDM), subgroup C (TheraCal LC), and subgroup D (MTA). Pulps were mechanically exposed in the middle of the cavity floor and capped with different materials. An assessment of periapical response was performed preoperatively and at 8 weeks. After 2 and 8-week intervals, the dogs were sacrificed, and the teeth were stained with hematoxylin-eosin and graded by using a histologic scoring system. Statistical analysis was performed using the chi-square and Kruskal-Wallis tests (p = 0.05). RESULTS: All subgroups showed mild inflammation with normal pulp tissue at 2 weeks with no significant differences between subgroups (p ≤ 0.05), except for the TheraCal LC subgroup, which exhibited moderate inflammation (62.5%). Absence of a complete calcified bridge was reported in all subgroups at 2 weeks, while at 8 weeks, the majority of samples in the LCG-TDM and MTA-Angelus subgroups showed complete dentin bridge formation and absence of inflammatory pulp response with no significant differences between them (p ≤ 0.05). However, the formed dentin in the LCG-TDM group was significantly thicker, with layers of ordered odontoblasts identified to create a homogeneous tubular structure and numerous dentinal tubule lines suggesting a favourable trend towards dentin regeneration. TheraCal LC samples revealed a reasonably thick dentin bridge with moderate inflammation (50%) and LCG showed heavily fibrous tissue infiltrates with areas of degenerated pulp with no signs of hard tissue formation. CONCLUSIONS: LCG-TDM, as an extracellular matrix-based material, has the potential to regenerate dentin and preserve pulp vitality, making it a viable natural alternative to silicate-based cements for healing in vivo dentin defects in direct pulp-capping procedures.

Spectrophotometric Analysis of Color Stability Induced by Various Calcium Silicate Cements in Full Pulpotomy of Permanent Molars: Theracal PT, Biodentine, and ProRoot MTA.

AIM: The objective of this study was to assess the color stability induced by Theracal PT, Biodentine, and ProRoot MTA in teeth subjected to full pulpotomy, over a span of 6 months. MATERIALS AND METHODS: The study employed a total of 48 freshly extracted intact human third molar teeth. Samples were randomly assigned into four groups (n = 12). All teeth, with the exception of the control group, underwent endodontic access. All materials were mixed in accordance with the manufacturer's guidelines and applied at a thickness of 3 mm at the orifice level before they set. The study groups were negative control (was not prepared), positive control (ProRootMTA), Biodentine, and Theracal PT. Glass ionomer and composite resin material was applied to the cavities. The color measurements were performed using the VITA Easy Shade spectrophotometer. All measurements were repeated 3 times in the determined area on the middle buccal surface of the tooth at baseline that (T0); after access preparation and material placement and setting) and then subsequently at 7 (T1), 30 (T2), 90 (T3), and T4 (180) days later. Data were statistically analyzed by using Kruskal-Wallis H at a confidence level of 95% (P < .05). RESULTS: Compared with the negative control group, Biodentine and Theracal PT showed color stability (ΔE ≤ 3.7). The teeth treated with MTA showed clinically observable discoloration (ΔE ≥ 3.7) at T0, T1, T2, T3, and T4 intervals. At all-time intervals, the MTA group induced more discoloration than Biodentine and Theracal PT (P < .05). CONCLUSIONS: Theracal PT and Biodentine caused least discoloration compared to PMTA even 6 months after its application in teeth undergoing pulpotomy, thereby offering clinicians a reliable alternative for use in the esthetic zone.

Effect of Recombinant Human Platelet-Derived Growth Factor on Healing of Chronic Periapical Tissue Pathosis Following Apical Surgery in a Canine Model: A Histomorphometric and Microcomputed Tomography Analysis.

This canine in vivo study assessed the effect of recombinant human platelet-derived growth factor (rhPDGF) on the healing of periapical tissues following apical surgery. From a total of 96 premolar teeth, 64 teeth from six beagle dogs (2 years old) were classified as experimental and were randomly assigned to four experimental groups (16 teeth per group). After having the pulp extirpated, leaving teeth open to the oral cavity for 1 week, and sealing with an immediate restorative material for 8 weeks, nonsurgical endodontic treatment was performed. A split-mouth design was used, and intra-animal randomization of treatment sides was applied to the groups as follows: apical curettage + 1.5-mm root-end resection (Group 1); apicoectomy + mineral trioxide aggregate (MTA) root-end filling (Group 2); apicoectomy + MTA root-end filling + rhPDGF (Group 3); and apical curettage + rhPDGF (Group 4). The animals were sacrificed 24 months after apical surgery, and histologic and µCT analyses were performed for bone volume loss (BVL). Group 1 showed partial resolution of the periapical lesions without signs of tissue regeneration (BVL: 49.09 ± 10.97 mm3). Group 2 had minimal bone regeneration and showed cementum reformation in 9 teeth, with no direct attachment to the MTA (BVL: 35.34 ± 10.97 mm3). Group 3 showed regeneration of all damaged apical tissues without direct contact between the cementum and MTA (BLV: 4.51 ± 1.55 mm3). Group 4 showed regeneration of PDL, bone, and cementum and attachment of functional cementum fibers (BVL: 2.82 ± 2.3 mm3). The difference in BVL was statistically significant only for Groups 1 and 2 (P < .05). rhPDGF may help regenerate apical tissue structures following apical surgery.

Mutations at proximal cysteine residues in PML impair ATO binding by destabilizing the RBCC domain.

Acute promyelocytic leukemia (APL) is characterized by the fusion gene promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) and is conventionally treated with arsenic trioxide (ATO). ATO binds directly to the RING finger, B-box, coiled-coil (RBCC) domain of PML and initiates degradation of the fusion oncoprotein PML-RARA. However, the mutational hotspot at C212-S220 disrupts ATO binding, leading to drug resistance in APL. Therefore, structural consequences of these point mutations in PML that remain uncertain require comprehensive analysis. In this study, we investigated the structure-based ensemble properties of the promyelocytic leukemia-RING-B-box-coiled-coil (PML-RBCC) domains and ATO-resistant mutations. Oligomeric studies reveal that PML-RBCC wild-type and mutants C212R, S214L, A216T, L217F, and S220G predominantly form tetramers, whereas mutants C213R, A216V, L218P, and D219H tend to form dimers. The stability of the dimeric mutants was lower, exhibiting a melting temperature (Tm) reduction of 30 °C compared with the tetrameric mutants and wild-type PML protein. Furthermore, the exposed surface of the C213R mutation rendered it more prone to protease digestion than that of the C212R mutation. The spectroscopic analysis highlighted ATO-induced structural alterations in S214L, A216V, and D219H mutants, in contrast to C213R, L217F, and L218P mutations. Moreover, the computational analysis revealed that the ATO-resistant mutations C213R, A216V, L217F, and L218P caused changes in the size, shape, and flexibility of the PML-RBCC wild-type protein. The mutations C213R, A216V, L217F, and L218P destabilize the wild-type protein structure due to the adaptation of distinct conformational changes. In addition, these mutations disrupt several hydrogen bonds, including interactions involving C212, C213, and C215, which are essential for ATO binding. The local and global structural features induced by these mutations provide mechanistic insight into ATO resistance and APL pathogenesis.

4-Year Pulp Survival in a Randomized Trial on Direct Pulp Capping.

INTRODUCTION: This study aimed to assess pulp survival in a randomized trial on pulp lavage in adult nonpainful posterior teeth with carious pulp exposure. The treatment included complete caries excavation, direct pulp capping with mineral trioxide aggregate, and immediate restoration with composite resin. METHODS: Fluid was collected from the pulp wound to assess matrix metalloproteinase-9 (MMP-9) and total protein values. Before pulp capping, cavities were randomly (block randomization, n = 48) washed with a physiological saline or a sodium hypochlorite solution (2.5% NaOCl). Treatment outcome was assessed clinically (cold test) and radiographically after at least 1 year and again after at least 3 years. Painful failures were differentiated from nonpainful failures. Pulp survival was estimated using the Kaplan-Meier method including 95% confidence intervals (CIs) up to 1500 days. RESULTS: From the 96 patients originally enrolled, 73 individuals could be followed continuously. The clinical observations indicated a beneficial and sustained effect of pulp lavage with 2.5% NaOCl over a control treatment with physiological saline solution on estimated pulp survival 1500 days postintervention, with 7% (95% CI, 1%-40%) in the saline group versus 55% (95% CI, 30%-100%) in the NaOCl group. High MMP-9/total protein values in pulpal fluid collected from the exposed site indicated early and painful treatment failures yet were not associated with failures that occurred more than 250 days after intervention. CONCLUSIONS: The low 4-year success rates reported here challenge the concept of direct pulp capping in the cases that were included. NaOCl lavage did not only increase the survival of affected pulps substantially but also particularly diminished painful failures (33% in the NaOCl group vs 62% in the saline group). The lack of the predictive value of MMP-9 assessments beyond early treatment failures points to inflammatory states of the pulp tissue under deep caries, which are not related to neutrophil infiltration.

Gelling Bodies: Understanding the Mechanisms Underlying Arsenic Trioxide Action.

SUMMARY: The study by Bercier and colleagues investigates the mechanisms of action of arsenic trioxide (ATO). The authors find that ATO promotes transition of PML nuclear bodies to a gel-like state via the PML trimerization domain and a critical cysteine residue. Overall, this work sheds new light onto how PML-RARα, the oncogene of APL, is targeted by ATO for disease eradication. See related article by Bercier et al., p. 2548 (6).