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.

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.

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.

[Tobacco heated products: a new challenge in tobacco control]. / Los productos de tabaco calentado: nuevo reto en el control del tabaco.

As cigarette sales decline, the tobacco industry has turned to the sale of heated tobacco products (HTP), which are on the rise. We are concerned with reports erroneously indicating that heated tobacco is associated with a lower risk of cancer and other diseases than conventional cigarettes, citing as a source the Food and Drug Administration (FDA) of the United States. The FDA has indeed authorized the sale of an HTP, but denies that this approval is an endorsement of the product or that it is safe. Philip Morris asked the FDA to approve this product as a "modified risk" tobacco product. However, the Agency denied that the risk to users' health was less than conventional cigarettes, despite emitting less amount of some toxicants. Spain and the European Union should end the regulatory privileges that HTPs have until now. We identified at least five aspects to improve: 1) compliance with the prohibition of HTPs use where smoking is prohibited; 2) control of the prohibition of advertising, promotion, and sponsorship of HTPs; 3) that HTPs carry the same type of labeling as cigarettes; 4) limit that HTPs have characteristic aromas; and 5) treat HTPs fiscally at the same level as cigarettes.

Melatonin Treatment Alters Biological and Immunomodulatory Properties of Human Dental Pulp Mesenchymal Stem Cells via Augmented Transforming Growth Factor Beta Secretion.

INTRODUCTION: Melatonin is an endogenous neurohormone with well-reported anti-inflammatory and antioxidant properties, but the direct biological and immunomodulatory effects of melatonin on human dental pulp stem cells (hDPSCs) has not been fully elucidated. The aim of this study was to evaluate the influence of melatonin on the cytocompatibility, proliferation, cell migration, odontogenic differentiation, mineralized nodule formation, and immunomodulatory properties of hDPSCs. METHODS: To address the melatonin biological effects on hDPSCs, the cytocompatibility, proliferation, cell migration, odontogenic differentiation, mineralized nodule formation, and immunomodulatory properties of hDPSCs after melatonin treatment were evaluated. The statistical differences were evaluated using 1-way analysis of variance with the Tukey multiple comparison test. RESULTS: We found that melatonin did not alter hDPSC immunophenotype or cell viability, even at the highest concentrations used. However, using intermediate melatonin concentrations (10-300 µmol/L), a significantly higher proliferation rate (P < .05 and P < .01) and migration of hDPSCs (P < .01) were observed. Importantly, melatonin treatment (100 µmol/L) significantly increased the secretion of the anti-inflammatory cytokine transforming growth factor beta (P < .05 and P < .01) and provoked a more robust antiproliferative effect on mitogen-stimulated T cells (P < .05). Finally, and unlike previous results found with mesenchymal stem cells from other sources, melatonin fails to induce or accelerate the spontaneous osteogenic differentiation of hDPSCs. CONCLUSIONS: Together, these findings provide key data on the bioactivity of melatonin and its effects on hPDSC biological and immunomodulatory properties.

Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats.

Medication-related osteonecrosis of the jaw (MRONJ) is defined as the exposed necrotic bone involving the maxillofacial structures in bisphosphonate treated patients, and the pathophysiology of this disease remains unclear. The aim of this study was to assess the effects of the allogeneic transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a model of Wistar mice with induced MRONJ disease. BM-MSCs from five male Wistar rats were characterized and cultured on ß-tricalcium phosphate (ß-TCP) granules. Thirty female Wistar rats were injected intraperitoneally with zoledronic acid and afterwards upper jaw molars were extracted. The animals were randomized to receive: Group 1: 1 × 106 BM-MSCs/ß-TCP construct in the alveolar socket; and Group 2: Saline solution/ß-TCP construct. A clinical and histological analysis was performed. Nested polymerase chain reaction (PCR) was assessed to verify the presence of transplanted male rat cells in the female recipient jaws. Clinical and histological findings evidenced that none of the animals in Group 1 exhibited uncovered sockets or bone exposure associated to MRONJ, whereas we detected 33% of MRONJ cases in Group 2. In addition, male rat cells were detected in the maxillae site four weeks after transplantation in the BM-MSCs-group. Allogeneic BM-MSCs in extractions sites ameliorates MRONJ incidence in zoledronic acid-treated rats compared to non-MSC treatments.

Preclinical Studies of the Biosafety and Efficacy of Human Bone Marrow Mesenchymal Stem Cells Pre-Seeded into ß-TCP Scaffolds after Transplantation.

Background: Cell-Based Therapies (CBT) constitute a valid procedure for increasing the quantity and quality of bone in areas with an inadequate bone volume. However, safety and efficacy should be investigated prior to clinical application. The objective of this study was to evaluate the biodistribution, safety and osteogenic capacity of bone marrow-derived human mesenchymal stem cells (hBMMSCs) pre-seeded into ß-tricalcium phosphate (TCP) and implanted into NOD/SCID mice at subcutaneous and intramuscular sites. Methods: hBMMSCs were isolated, characterized and then cultured in vitro on a porous ß-TCP scaffold. Cell viability and attachment were analyzed and then hBMMSCs seeded constructs were surgically placed at subcutaneous and intramuscular dorsal sites into NOD/SCID mice. Acute and subchronic toxicity, cell biodistribution and efficacy were investigated. Results: There were no deaths or adverse events in treated mice during the 48-hour observation period, and no toxic response was observed in mice. In the 12-week subchronic toxicity study, no mortalities, abnormal behavioral symptoms or clinical signs were observed in the saline control mice or the hBMMSCs/ß-TCP groups. Finally, our results showed the bone-forming capacity of hBMMSCs/ß-TCP since immunohistochemical expression of human osteocalcin was detected from week 7. Conclusions: These results show that transplantation of hBMMSCs/ß-TCP in NOD/SCID mice are safe and effective, and might be applied to human bone diseases in future clinical trials.

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.

Silk-Fibroin and Graphene Oxide Composites Promote Human Periodontal Ligament Stem Cell Spontaneous Differentiation into Osteo/Cementoblast-Like Cells.

Graphene represents one of the most interesting additions to the tissue engineering toolbox. Novel graphene-based composites are required to improve the beneficial graphene properties in terms of tridimensional polymeric structure, conferring a higher mechanical strength and favoring the differentiation of human mesenchymal stem cells. Here, we have demonstrated in a wide range of composite combinations, the successful use of graphene and silk-fibroin constructs for future bioengineering applications in the field of clinical regenerative dentistry using human periodontal ligament stem cells. Our results provide exciting new data for the development of suitable scaffolds that allow good cell engrafting, preservation of cell viability and proliferation, promotion of spontaneous osteoblastic differentiation, and importantly, stimulation of a higher cementum physiological synthesis than using other different available biomaterials.

Cytoprotective effects of melatonin on zoledronic acid-treated human mesenchymal stem cells in vitro.

OBJECTIVE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common clinical complication in patients receiving bisphosphonate therapy. Furthermore, melatonin has been proposed as a therapeutic drug for the oral cavity due to its antioxidant properties. This study aimed to evaluate the cytoprotective effects of melatonin on zoledronic acid (ZA)-treated human mesenchymal stem cells from periodontal ligament (PDLSCs) and bone marrow (BMMSCs). METHODS: PDLSCs and BMMSCs were exposed to ZA, melatonin or ZA + melatonin for 72 h. Cell proliferation was measured by a colorimetric assay, whereas their mesenchymal phenotype was analyzed by flow cytometry. RESULTS: Proliferation assays showed that BMMSCs presented higher ZA resistance than PDLSCs, as well as a difference in response to the simultaneous treatment of ZA + melatonin. Using PDLSCs, high doses of melatonin significantly increased their proliferation, whereas lower concentrations were enough to enhance ZA-treated BMMSC proliferation. Moreover, PDLSCs displayed a CD90/CD105 downregulation and CD73 upregulation in response to ZA, which was more pronounced in response to melatonin. Furthermore, ZA or ZA + low doses of melatonin induced a decrease of expression of CD90/CD105/CD73 on BMMSCs, while a higher concentration recovered CD73 levels. CONCLUSION: These results suggest that melatonin has a cytoprotective effect on ZA-treated PDLSCs and BMMSCs. Thus, it could be used for BRONJ prevention.

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.

Human adult periodontal ligament-derived cells integrate and differentiate after implantation into the adult mammalian brain.

Previous studies suggest that neural crest (NC)-derived stem cells may reside in NC derivatives including the human periodontal ligament (hPDL). The isolation and manipulation of autologous NC-derived cells could be an accessible source of adult neural stem cells for their use in cell replacement and gene transfer to the diseased central nervous system. In this study, we examined the expression of NC markers and neural differentiation potential of hPDL-derived cells both in vitro and in vivo. In vitro we found that hPDL-derived cells expressed stem cell markers (Oct3/4, Nestin, Sox2, and Musashi-1) and a subset of NC cell markers (Slug, p75(NTR), Twist, and Sox9). hPDL-derived cells differentiated into neural-like cells based on cellular morphology and neural marker expression (TUJ1, MAP2, MAP1b, GAD65/67, GABA, NeuN, ChAT, GAT1, synaptophysin, GFAP, NG2, and O4). In vivo, hPDL-derived cells survive, migrate, and give rise to DCX(+), NF-M(+), GABA(+), GFAP(+), and NG2(+) cells after grafting the adult mouse brain. Some of the grafted hPDL-derived cells were located in stem cell niches such as the ventricular epithelium and the subventricular zone of the anterolateral ventricle wall as well as in the subgranular zone of the hippocampal dentate gyrus. Thus, the hPDL contains stem cells that originate from the NC and can differentiate into neural cells. The engraftment and differentiation properties of hPDL-derived cells in the adult brain indicate that they are a potential stem cell source to be used in neuroregenerative and/or neurotrophic medicine.

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.

Neuropathic orofacial pain after dental implant placement: review of the literature and case report.

Persistent and chronic pain is more common in the head and neck region than in any other part of the body; therefore, dentists are more likely to encounter these rather complex cases in their practices. In this report, we present a brief review of neuropathic orofacial pain (NOP) that can begin after deafferentation of trigeminal nerve fibers after root canal treatment, apicoectomy, tooth extraction, or implant placement or idiopathically. A case of NOP occurring after a surgical implant procedure in a 62-year-old woman is presented. Continuous pain started 6 months after the placement of 8 dental implants in the maxilla, at the time of positioning the prosthesis on her implants. After being subjected to a physical examination and relevant complementary radiologic imaging, the patient was diagnosed with an NOP secondary to nerve impingement due to dental implant placement as well as myofascial head and neck pain.

Knowledge of oral cancer and preventive attitudes of Spanish dentists. Primary effects of a pilot educational intervention.

OBJECTIVE: To assess the knowledge and preventive attitudes that Spanish dentists have towards oral cancer, before and after an educational intervention. METHODS: A quasi-experimental study based on a nationwide intervention. All Spanish dentists were offered an on-site course on oral cancer. An individual questionnaire was administered before and after attending the course. The main outcome measures were systematic examination of the oral cavity, promotion of healthy habits and knowledge of clinical aspects. RESULTS: 440 GDPs entered the study. Age: 40.7+/-10.7, range 21-74. Professional experience: 13.9+/-8.9 years, range 0-45. Of those who participated in the study, 53.1% had never attended a course on oral cancer, 72.4% stated that they perform a systematic examination of the oral mucosa, 88.2% provided systematic counselling on tobacco cessation, and 54.7% reported that they did the same for alcohol. In addition, 32.3% advised patients to eat fruits and vegetables high in antioxidants. Professional experience was significantly associated with oral mucosa systematic examination (t= 2.9; p=0.003), advice on alcohol consumption (t=5.0; p=0.000), and on fruit and vegetable intake (t=5.1; p<0.001). None of these practices were specifically associated with knowledge on oral cancer. All areas of knowledge examined showed statistically significant improvement after the educational intervention. CONCLUSIONS: The intervention appears to have improved the GDP s knowledge, confirming the importance of this national campaign.