Biocompatibility, bioactivity and immunomodulatory properties of three calcium silicate-based sealers: an in vitro study on hPDLSCs.

OBJECTIVES: To assess the biocompatibility, bioactivity, and immunomodulatory properties of three new calcium silicate cement-based sealers: Ceraseal (CS), Totalfill BC Sealer (TFbc) and WellRoot ST (WR-ST) on human periodontal ligament stem cells (hPDLSCs). MATERIALS AND METHODS: HPDLSCs were isolated from extracted third molars from healthy patients. Eluates (1:1, 1:2, and 1:4 ratio) and sample discs of CS, TFbc and WR-ST after setting were prepared. A series of assays were performed: cell characterization, cell metabolic activity (MTT assay) cell attachment and morphology (SEM assay), cell migration (wound-healing assay), cytoskeleton organization (phaloidin-based assay); IL-6 and IL-8 release (ELISA); differentiation marker expression (RT-qPCR assay), and cell mineralization (Alizarin Red S staining). HPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media were used as a comparison. Statistical significance was established at p < 0.05. RESULTS: All the tested sealers exhibited similar results in the cytocompatibility assays (cell metabolic activity, migration, attachment, morphology, and cytoskeleton organization) compared with a negative control group. CS and TFbc exhibited an upregulation of at least one osteo/cementogenic marker compared to the negative and positive control groups. CS and TFbc also showed a significantly higher calcified nodule formation than the negative and positive control groups. Both the marker expression and calcified nodule formation were significantly higher in CS-treated cells than TFbc treated cells. WR-ST exhibited similar results to the control group. CS and TFbc-treated cells exhibited a significant downregulation of IL-6 after 72 h of culture compared to the negative control group (p < 0.05). CONCLUSION: All the tested sealers exhibited an adequate cytocompatibility. CS significantly enhances cell differentiation by upregulating the expression of key genes associated with bone and cementum formation. Additionally, CS was observed to facilitate the mineralization of the extracellular matrix effectively. In contrast, the effects of TFbc and WR-ST on these processes were less pronounced compared to CS. Furthermore, both CS and TFbc exhibited an anti-inflammatory potential, contributing to their potential therapeutic benefits in regenerative endodontics. CLINICAL RELEVANCE: This is the first study to compare the biological properties and immunomodulatory potential of Ceraseal, Totalfill BC Sealer, and WellRoot ST. The results act as supporting evidence for their use in root canal treatment.

Comparative bioactivity and immunomodulatory potential of the new Bioroot Flow and AH Plus Bioceramic sealer: An in vitro study on hPDLSCs.

OBJECTIVES: To evaluate the cytocompatibility, bioactivity, and anti-inflammatory potential of the new pre-mixed calcium silicate cement-based sealers Bioroot Flow (BrF) and AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared to the epoxy resin-based sealer AH Plus (AHP). MATERIALS AND METHODS: Standardized discs and 1:1, 1:2, and 1:4 eluates of BrF, AHPbcs and AHP after setting were prepared. The following assays were performed: cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, cytoskeleton organization via immunofluorescence staining; cytokine release via ELISA; osteo/cemento/odontogenic marker expression via RT-qPCR, and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars from healthy patients. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p < 0.05. RESULTS: Both BrF and AHPbcs showed significantly positive results in the cytocompatibility assays (cell metabolic activity, migration, attachment, morphology, and cytoskeleton organization) compared with a negative control group, while AHP showed significant negative results. BrF exhibited an upregulation of at least one osteo/cementogenic marker compared to the negative and positive control groups. BrF showed a significantly higher calcified nodule formation than AHPbcs, the negative and positive control groups, while AHPbcs was higher than the negative control group. Both were also significantly higher than AHP group. CONCLUSION: BrF and AHPbcs exhibit adequate and comparable cytocompatibility on hPDLSCs. BrF also promoted the osteo/cementogenic differentiation of hPDLSCs. Both calcium silicate-based sealers favored the downregulation of the inflammatory cytokine IL-6 and the calcified nodule formation from hPDLSCs. BrF exerted a significantly higher influence on cell mineralization than AHPbcs. CLINICAL RELEVANCE: This is the first study to elucidate the biological properties and immunomodulatory potential of Bioroot Flow and AH Plus Bioceramic Sealer. The results act as supporting evidence for their use in root canal treatment.

Effect of milled and lithography-based additively manufactured zirconia (3Y-TZP) on the biological properties of human osteoblasts.

STATEMENT OF PROBLEM: Lithography-based additively manufactured (AM) zirconia has been used to fabricate dental implants and custom barriers for guided bone regeneration procedures. However, studies on the effect of AM zirconia on the biological properties of human osteoblasts are lacking. PURPOSE: The purpose of this in vitro study was to compare the effect of milled and lithography-based AM zirconia on the biological properties of normal human osteoblasts (NHOsts), as well as to compare the chemical composition between the milled and lithography-based AM 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) zirconia. MATERIAL AND METHODS: Three mol percentage yttria-stabilized tetragonal zirconia polycrystal disks (Ø6×2-mm) were fabricated using subtractive milling (Priti multidisc ZrO2 monochrome) (M group) and lithography-based additive manufacturing methods (LithaCon 3Y 210) (AM group) (n=10). NHOsts were exposed to different material extracts (1:1, 1:2, and 1:4) and cytotoxicity, cell migration, cell morphology, and cell attachment biological tests were completed. Additionally, for morphological and chemical analysis, a scanning electronic microscopy with energy-dispersive X-ray analysis (SEM/EDX) evaluation was completed. Data were analyzed by using 1-way ANOVA and the Dunnett test (α=.05). RESULTS: Substantial cell attachment and spreading were observed in both material surfaces. The presence of zirconium was evident in both groups, although the percentage of zirconium in the AM group (64.7%) was slightly higher than in the M group (52.6%). When NHOsts were cultured in the presence of the different material eluates, the M and AM groups exhibited similar NHOst viability and migration rates when compared with untreated cells; no significant differences were found (P>.05). CONCLUSIONS: The lithography-based AM zirconia tested showed adequate cytocompatibility without differences when compared with the milled zirconia (M group) specimens. Slight chemical element composition differences were found between milled and lithography-based AM zirconia.

Cytocompatibility and bioactive potential of AH Plus Bioceramic Sealer: An in vitro study.

AIM: To assess the cytocompatibility and bioactive potential of the new calcium silicate cement-based sealer AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared with the epoxy resin-based sealer AH Plus (AHP) and the calcium silicate cement-based sealer Endosequence BC Sealer (ESbcs). METHODOLOGY: Standardized sample discs and 1:1, 1:2 and 1:4 eluates of the tested materials were prepared. The following assays were performed: surface element distribution via SEM-EDX, cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, osteo/cemento/odontogenic marker expression via RT-qPCR and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p < .05. RESULTS: A higher peak of Ca2 + was detected from ESbcs compared with AHPbcs and AHP in SEM-EDX. Both AHPbcs and ESbcs showed significantly positive results in the cytocompatibility assays (cell viability, migration/proliferation, attachment and morphology) compared with a negative control group, whilst AHP showed significant negative results. Both AHPbcs and ESbcs exhibited an upregulation of at least one osteo/odonto/cementogenic marker compared with the negative and positive control groups. Both ESbcs and AHPbcs showed a significantly higher calcified nodule formation than the negative and positive control groups, indicative of their biomineralization potential and were also significantly higher than AHP group. CONCLUSION: AH Plus Bioceramic Sealer exhibited a significantly higher cytocompatibility and bioactive potential than AH Plus and a similar cytocompatibility to that of Endosequence BC Sealer. Endosequence BC Sealer exhibited a significantly higher mineralization potential than the other tested sealers. The results from this in vitro study act as supporting evidence for the use of AH Plus Bioceramic Sealer in root canal treatment.

Scientific production on silicate-based endodontic materials: evolution and current state: a bibliometric analysis.

OBJECTIVES: To perform a bibliometric analysis on silicate-based biomaterials in endodontics; to elucidate the evolution and distribution of scientific production regarding research on these biomaterials, the authors and institutions involved, and the most used descriptors/keywords in this field. MATERIALS AND METHODS: A general advanced broad search was performed in Web of Science Core Collection, using the terms "Silicate" and "Endod*." By means of the "Analyze Results" and "Citation Analysis" tools from Web of Science, bibliometric data were extracted. Bibliometric networks on co-authorship and keyword co-occurrence were illustrated using VOSviewer software tool. RESULTS: Research in the field of silicate-based endodontic materials in endodontics has followed an exponential crescent tendency over the period between 1995 and 2020. Two major co-authorship networks lead the research production in the field, headed by Gandolfi MG and Prati C, and Rodríguez-Lozano FJ and Forner L; respectively. "Mineral trioxide aggregate," "MTA", "Biocompatibility," "Biodentine," and "In vitro" were the terms with the highest occurrence. The modal study type in this research area are laboratory studies, representing 77.7% of the total number of records. The relationship between keywords illustrates the recent tendency to assess biological properties of MTA and Biodentine, which could be extrapolated to other silicate-based materials. CONCLUSIONS: The results from the present study highlight the exponential increase and distribution of scientific production on silicate-based materials in endodontics, along with the modal keywords used as descriptors and the major authorship networks involved. The predominance of laboratory studies in this research field reinforces the need for clinical studies, to extrapolate the reported performance and characteristics of silicate-based materials into the clinical setting. CLINICAL RELEVANCE: The present study may aid the clinician's continuing education and evidence-based practice by providing knowledge and facilitating the literature search on the field of silicate-based biomaterials in endodontics.

Comparative cytocompatibility of the new calcium silicate-based cement NeoPutty versus NeoMTA Plus and MTA on human dental pulp cells: an in vitro study.

OBJECTIVES: The aim of the present in vitro study is to determine the cytocompatibility of the recently introduced NeoPutty in contact with human dental pulp cells compared with its precursor NeoMTA Plus and the classic gold standard MTA Angelus. MATERIALS AND METHODS: Sample disks were obtained for each of the tested materials (5 mm diameter; 2 mm thickness; n = 30), along with 1:1, 1:2, and 1:4 material eluents. HDPCs were extracted and cultured with the tested materials (test groups) or in unconditioned medium (control group), and the following biocompatibility assays were performed: MTT assay, scratch wound assay, cell cytoskeleton staining assays, and cell attachment assessment via SEM. Additionally, material ion release and surface element composition were evaluated via ICP-MS and SEM-EDX, respectively. Each experimental condition was carried out three times and assessed in three independent experiments. Statistical significance was established at p < 0.05. RESULTS: 1:2 dilutions of all the tested materials exhibited a comparable cell viability to that of the control group at 48 and 72 h of culture (p < 0.05). The same was observed for 1:4 dilutions of the tested materials at 24, 48, and 72 h of culture (p > 0.05). All the tested materials exhibited adequate cytocompatibility in the remaining biocompatibility assays. MTA exhibited a significantly higher calcium ion release compared to NeoPutty and NeoMTA Plus (p < 0.05). CONCLUSION: The results from the present work elucidate the adequate cytocompatibility of NeoPutty, NeoMTA Plus, and MTA Angelus towards human dental pulp cells. CLINICAL RELEVANCE: Within the limitations of the present in vitro study, our results may act as preliminary evidence for its use in vital pulp therapy as a pulp capper. However, results need to be interpreted with caution until further clinical supporting evidence is reported.

Cytocompatibility and bioactive properties of the new dual-curing resin-modified calcium silicate-based material for vital pulp therapy.

OBJECTIVE: The aim of the present study was to evaluate the in vitro biocompatibility of Theracal PT, Theracal LC, and MTA Angelus, considered as bioactive materials used for vital pulp treatment, on human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: Human dental pulp stem cells (hDPSCs) were isolated from third molars, and material eluates were prepared (undiluted, 1:2, and 1:4 ratios). The hDPSC cytotoxicity, adhesion, morphology, viability, and cell migration were assessed. The mineralization nodule formation was determined by Alizarin red S staining (ARS). The odonto/osteogenic differentiation potential was assessed by osteo/odontogenic marker expression real-time qPCR. The chemical composition and ion release of the vital pulp materials were determined by energy dispersive X-ray (EDX) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. Statistical differences were assessed by ANOVA and Tukey's test (p < 0.05). RESULTS: The three vital pulp materials showed variable levels of calcium, tungsten, silicon, and zirconium release and in their chemical composition. Cytocompatibility assays revealed higher hDPSC viability and migration rates when treated with Theracal PT than with Theracal LC. The lowest cell adhesion and spreading were observed in all Theracal LC-treated groups, whereas the highest were observed when treated with MTA. Theracal PT and MTA promoted the upregulation of DSPP and RUNX2 gene expression (p < 0.05). After 21 days, both MTA Angelus and Theracal PT-treated cells exhibited a significantly higher mineralized nodule formation than the negative control (p < 0.05). CONCLUSIONS: This study demonstrates the favorable in vitro cytocompatibility and bioactive properties of the recently introduced Theracal PT and the well-established MTA Angelus on hDPSCs, as opposed to Theracal LC. More studies, including in vivo animal testing are suggested before these new formulations might be used in the clinical setting. CLINICAL RELEVANCE: Theracal PT is a new material that could be clinically suitable for vital pulp therapy. Further studies considering its biocompatibility and bioactivity are necessary.

Analysis of the Adherence of Dental Pulp Stem Cells on Two-Dimensional and Three-Dimensional Silk Fibroin-Based Biomaterials.

Among various biomaterials used as scaffolds in tissue engineering, silk fibroin is a highly attractive material. A scaffold should be biocompatible and nontoxic, with optimal physical features and mechanical properties. For this reason, tissue-engineering approaches in regenerative medicine have focused on investigating the biocompatibility of possible biomaterials by analyzing cell-scaffold interaction properties. The aim of the present study was to examine the biocompatibility of silk fibroin as a film (two-dimensional [2D]) and a scaffold (three-dimensional [3D]) after being cellularized with human dental pulp stem cells (hDPSCs). Human dental pulp stem cells were isolated from healthy patients aged between 18 and 31 years. Further, silk fibroin-based 2D films and 3D scaffolds were prepared. Human dental pulp stem cells were directly seeded onto the biomaterial surfaces and their proliferation, adherence, and cell morphology were analyzed after 24, 120, and 168 hours. Additionally, the characteristics of the silk fibroin 2D films and 3D scaffolds before and after cell seeding were analyzed by scanning electron microscopy. After the initial 24 hours, silk fibroin-based 3D scaffolds displayed more adhered cells with a suitable fibroblastic morphology than those displayed on the 2D films. After longer culture times, hDPSCs proliferated sufficiently to cover the entire surface of the 3D silk fibroin scaffold, whereas the 2D films were only partially covered. Our results indicate the good in vitro biocompatibility of silk fibroin-based biomaterials, especially when 3D scaffolds rather than 2D films are used.

Use of Nanoparticles in Regenerative Dentistry: A Systematic Review.

INTRODUCTION: nanoparticles are tiny-sized materials whose characteristics and properties mean that their association with dental materials is being investigated to ascertain their effects and possible benefits on tooth structures. This systematic review aimed to qualitatively collect in vitro studies that address the potential application of different nanoparticles in dental regeneration. Following an exhaustive search and article selection process, 16 in vitro studies that met our eligibility criteria were included. BG-NPs were analyzed across five studies, with three demonstrating their impact on the growth and differentiation of human hDPSCs. CS-NPs were examined in three studies, with findings from two indicating a significant effect on the differentiation of SCAPs. Nanoparticles' therapeutic potential and their stimulatory effect on promoting the regeneration of cells of the dentin-pulp complex have been proven. Their effect is altered according to the type of nanoparticle, concentration, and substances associated with them and, depending on these variables, they will affect the pulp, dentine, and dental cementum differently.

Oral Manifestations in Pregnant Women: A Systematic Review.

Background: The period of pregnancy is characterized by a multitude of diverse changes that exert a notable impact on the oral cavity of women. During this gestational phase, patients necessitate tailored oral care and specific recommendations to preempt and address potential oral diseases. This systematic review aimed to perform a detailed analysis of the research studies that focused on the oral manifestations observed in pregnant women. Methods: A meticulous search was conducted in the databases Medline, Scopus, and Scielo by employing the following search terms: ((pregnant OR pregnancy)) AND (("oral manifestation*") OR ("oral health")). Articles that were published between 2013 and 2023 and written in English or Spanish and studies that scrutinized oral manifestations in pregnant women and included a diagnosis conducted by a qualified dentist were selected; we excluded articles published before 2013, articles that could not be accessed in full text, studies whose patients were not pregnant women at the time of the study, studies where patients were selected because they had a specific disease, studies where the clinical examination was not performed by a dentist, and articles written in languages other than English or Spanish. Subsequently, the risk of bias in the chosen articles was assessed in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scale. Results: A total of 20 studies were included in the analysis, following the exclusion and inclusion criteria. These studies were categorized as cross-sectional, cohort, longitudinal, or case-control. Various oral manifestations in pregnant women were examined, with five studies comparing these manifestations with those observed in nonpregnant women. Conclusions: The most prevalent oral manifestations associated with pregnancy encompass dental caries, periodontitis, gingivitis, pyogenic granuloma, and candidiasis. Nonetheless, less common lesions may also emerge during the course of pregnancy.

Comparative Cytotoxicity of Menthol and Eucalyptol: An In Vitro Study on Human Gingival Fibroblasts.

The aim of this study was to assess the influence of eucalyptol and menthol on the cell viability, migration, and reactive oxygen species production of human gingival fibroblasts (GFs) in vitro. Three different concentrations of eucalyptol and menthol were prepared following ISO 10993-5 guidelines (1, 5, and 10 mM). GFs were isolated from extracted teeth from healthy donors. The following parameters were assessed: cell viability via MTT, Annexin-V-FITC and 7-AAD staining, and IC50 assays; cell migration via horizontal scratch wound assay; and cell oxidative stress via reactive oxygen species assay. Data were analyzed using one-way ANOVA and Tukey's post hoc test. Statistical significance was established at p < 0.05. Eucalyptol and Menthol exhibited high cytotoxicity on gingival fibroblasts, as evidenced by cytotoxicity assays. Eucalyptol showed lower levels of cytotoxicity than menthol, compared to the control group. The cytotoxicity of the tested substances increased in a concentration-dependent manner. The same occurred in a time-dependent manner, although even 10 min of exposure to the tested substances showed a high cytotoxicity to the GFs. Commercially available products for oral application with these substances in their composition should be tested for cytotoxicity before their use.

Cell therapy in bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a clinical condition found in patients who have received intravenous or oral bisphosphonate therapy for various diseases related to bone. This report describes a novel treatment of BRONJ using autologous bone marrow stem cells, platelet-rich plasma, beta tricalcium phosphate, and demineralized bone matrix. STUDY DESIGN: We report a 71-year-old woman with history of multiple myeloma treated with intravenous zoledronic acid during 4 years. After a tooth extraction, the patient presented with a painful BRONJ lesion with no healing wound and cortical bone exposure. The patient was surgically managed with a standardized protocol of autologous stem cell therapy combining bone marrow harvest, cell concentration procedures, and intraoral surgery. RESULTS: CT scan performed 6 months later showed improvement of bone and concentric ossification. Cellular therapy might be considered a new strategy to heal BRONJ lesions.

Oral Manifestations of Mucormycosis: A Systematic Review.

Mucormycosis is a rare, opportunistic, and emerging fungal infection that can rapidly develop into a severe, highly fatal clinical picture. In most cases, it is caused by fungi of the order Mucorales, which are usually avirulent but become pathogenic when the host's immune system is compromised. This systematic review was conducted according to PRISMA guidelines. The databases searched included PubMed, Scopus, and Web of Science. We chose articles that analyzed the oral manifestations of patients with mucormycosis, were published between 2018 and 2023, and met our search terms. The risk of bias in the articles was assessed using the CARE guideline for case reports and STROBE for a cross-sectional study. After the selection process, 20 articles were included in this review, all containing information about the different oral manifestations presented by people with mucormycosis. The most common oral manifestations are mainly bone exposures and oral ulcers, halitosis, pus discharge, gingival thickening, and periodontitis. However, despite the importance of recognizing these oral manifestations in the early stages of mucormycotic infection, providing early treatment, and reducing the high mortality rate of the infection, more studies are needed.

Tissue engineering with dental pulp stem cells: isolation, characterization, and osteogenic differentiation.

INTRODUCTION: Dental pulp stem cells (DPSCs) are adult mesenchymal stem cells that have the ability to differentiate into osteoblasts, a fact that is very interesting in the context of tissue engineering. Our purpose was to isolate and characterize DPSCs and to compare the differentiation potential of 3 different osteogenic media. PATIENTS AND METHODS: Human dental pulp extracted from healthy young adults was placed in flasks with a mesenchymal expansion medium. At passage 4 DPSCs were analyzed for cell-cycle stage, proliferation, viability, and immunophenotype. DPSCs were grown in 3 different osteogenic media for 40 days. Flasks were incubated at 37 °C in 5% CO2, and the medium was changed twice a week. At day 40, the mineralization of the matrix was determined with Alizarin Red S dye. RESULTS: After osteogenic induction, DPSCs developed mineralization nodules (clusters), as revealed by Alizarin Red staining. This staining was stronger in the Osteodiff (Miltenyi) medium when compared to the other osteogenic media. CONCLUSIONS: This study demonstrates the ability of DPSC to differentiate into osteoblasts, especially in the presence of Osteodiff (Miltenyi). DPSCs are therefore a good candidate model for the study of hard-tissue mineralization.

Mesenchymal dental stem cells in regenerative dentistry.

In the last decade, tissue engineering is a field that has been suffering an enormous expansion in the regenerative medicine and dentistry. The use of cells as mesenchymal dental stem cells of easy access for dentist and oral surgeon, immunosuppressive properties, high proliferation and capacity to differentiate into odontoblasts, cementoblasts, osteoblasts and other cells implicated in the teeth, suppose a good perspective of future in the clinical dentistry. However, is necessary advance in the known of growth factors and signalling molecules implicated in tooth development and regeneration of different structures of teeth. Furthermore, these cells need a fabulous scaffold that facility their integration, differentiation, matrix synthesis and promote multiple specific interactions between cells. In this review, we give a brief description of tooth development and anatomy, definition and classification of stem cells, with special attention of mesenchymal stem cells, commonly used in the cellular therapy for their trasdifferentiation ability, non ethical problems and acceptable results in preliminary clinical trials. In terms of tissue engineering, we provide an overview of different types of mesenchymal stem cells that have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs), and stem cells from apical papilla (SCAPs), growth factors implicated in regeneration teeth and types of scaffolds for dental tissue regeneration.

Special Care Patients and Caries Prevalence in Permanent Dentition: A Systematic Review.

Due to the increase in the population with special needs and the significant difficulty in their dental management, it is essential to analyze the caries prevalence in this group of patients. The systematic review was conducted following the PRISMA statement. A search was performed on 9 May 2022 and updated on 5 June 2022, in three databases: Pubmed, Scielo, and Cochrane library. Studies involving the analysis of caries in permanent teeth in patients with special needs were included. A total of 1277 studies were analyzed and 21 studies were selected. Quality assessments were performed using an adapted version of the STROBE guidelines. Among the analyzed groups (intellectual disabilities, human immunodeficiency virus infection, schizophrenia, down syndrome, drug addicts, adult heart transplant, kidney disease, diabetic, autism, psychiatric patients, cerebral palsy, and hemophilia), the highest prevalence of caries was observed in patients with intellectual disability, without differences between genders. However, there is a need for more studies with standardized methods for caries diagnosis to further investigate the prevalence of caries in permanent teeth in patients with special needs.

Vital Pulp Therapy of Permanent Teeth with Reversible or Irreversible Pulpitis: An Overview of the Literature.

Vital pulp therapy (VPT) has been recently proposed as an alternative approach even in symptomatic mature permanent teeth with deep caries' lesions, aiming to maintain the pulp vitality over time and/or to avoid non-surgical root canal therapy (NSRCT). However, to date, the diagnosis of reversible or irreversible pulpitis is only based on clinical pain quantity and quality, without precisely reflecting the pulp inflammation status. Therefore, the aim of the present study was to provide an overview based on the current scientific literature to demonstrate the clinical effectiveness of VPT on mature permanent teeth, validating the use of hydraulic calcium silicate-based cements and their role in pain management. VPT may be successfully applied not only in mature permanent teeth diagnosed with reversible pulpitis, but also in permanent dental elements with signs and symptoms of irreversible pulpitis. Hydraulic cements showed favorable outcomes in terms of decrease of pro-inflammatory mediators and of post-operative pain. Pain plays a central role in the chance to perform VPT in mature permanent teeth, since it may be considered as a pre-operative diagnostic criterion as well as a treatment success parameter. In addition, proper assessment of pulp inflammation and choice of appropriate materials are key factors in enhancing VPT success.

Current Status and Trends in Research on Caries Diagnosis: A Bibliometric Analysis.

There are a wide variety of devices for the detection and diagnosis of caries from the initial stages. The purpose of this study was to perform a bibliometric study on research regarding caries diagnosis by identifying the contributing researchers, organizations, countries or regions, journals, and to provide an analysis of keyword co-occurrence and co-authorship networks. An advanced search was performed in Web of Science (WOS) Core Collection database, using the terms "caries diagno*" and "caries detect*" in the "topic" field, from 2013 to 2021. Bibliometric parameters were extracted using WOS's analyze results tools and VOSviewer software. A total of 816 documents were identified. Most of them, (61.3%) are included in "Dentistry Oral Surgery & Medicine" category within WOS. The largest scientific production on the subject is observed between 2018 and 2021, with a total of 344 records. The most productive author is Mendes FM, followed by Braga MM. The journal with the most articles published on caries diagnosis is Caries Research, with 55 articles (6.74%). The terms with the highest co-occurrence refer to the validity of diagnostic methods, tools or principles used in diagnosis or general aspects related to caries detection and diagnosis.

Dexamethasone and Doxycycline Doped Nanoparticles Increase the Differentiation Potential of Human Bone Marrow Stem Cells.

Non-resorbable polymeric nanoparticles (NPs) are proposed as an adjunctive treatment for bone regenerative strategies. The present in vitro investigation aimed to evaluate the effect of the different prototypes of bioactive NPs loaded with zinc (Zn-NPs), doxycycline (Dox-NPs) or dexamethasone (Dex-NPs) on the viability, morphology, migration, adhesion, osteoblastic differentiation, and mineralization potential of human bone marrow stem cells (hBMMSCs). Cell viability, proliferation, and differentiation were assessed using a resaruzin-based assay, cell cycle analysis, cell migration evaluation, cell cytoskeleton staining analysis, Alizarin Red S staining, and expression of the osteogenic-related genes by a real-time quantitative polymerase chain reaction (RT-qPCR). One-Way ANOVA and Tukey's test were employed. The resazurin assay showed adequate cell viability considering all concentrations and types of NPs at 24, 48, and 72 h of culture. The cell cycle analysis revealed a regular cell cycle profile at 0.1, 1, and 10 µg/mL, whereas 100 µg/mL produced an arrest of cells in the S phase. Cells cultured with 0.1 and 1 µg/mL NP concentrations showed a similar migration capacity to the untreated group. After 21 days, mineralization was increased by all the NPs prototypes. Dox-NPs and Dex-NPs produced a generalized up-regulation of the osteogenic-related genes. Dex-NPs and Dox-NPs exhibited excellent osteogenic potential and promoted hBMMSC differentiation. Future investigations, both in vitro and in vivo, are required to confirm the suitability of these NPs for their clinical application.

Biomimetic Approaches in Clinical Endodontics.

In the last few decades, biomimetic concepts have been widely adopted in various biomedical fields, including clinical dentistry. Endodontics is an important sub-branch of dentistry which deals with the different conditions of pulp to prevent tooth loss. Traditionally, common procedures, namely pulp capping, root canal treatment, apexification, and apexigonesis, have been considered for the treatment of different pulp conditions using selected materials. However, clinically to regenerate dental pulp, tissue engineering has been advocated as a feasible approach. Currently, new trends are emerging in terms of regenerative endodontics which have led to the replacement of diseased and non-vital teeth into the functional and healthy dentine-pulp complex. Root- canal therapy is the standard management option when dental pulp is damaged irreversibly. This treatment modality involves soft-tissue removal and then filling that gap through the obturation technique with a synthetic material. The formation of tubular dentine and pulp-like tissue formation occurs when stem cells are transplanted into the root canal with an appropriate scaffold material. To sum up tissue engineering approach includes three components: (1) scaffold, (2) differentiation, growth, and factors, and (3) the recruitment of stem cells within the pulp or from the periapical region. The aim of this paper is to thoroughly review and discuss various pulp-regenerative approaches and materials used in regenerative endodontics which may highlight the current trends and future research prospects in this particular area.