Background: During phagocytosis or stimulation with bacterial components, macrophages activate various cell processes, including the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are critical for successful defense against invading organisms. Increased levels of ROS/RNS create oxidative stress that results in tissue and bone destruction. Grape seed proanthocyanidins have been reported to possess a wide range of biologic properties against oxidative stress. In the present study, we investigated the effects of a grape seed proanthocyanidin extract (GSE) and commercial polyphenols on the production of ROS and RNS and on the protein expression of inducible nitric oxide synthase (iNOS) by murine macrophages stimulated with lipopolysaccharides (LPS) of periodontopathogens.Methods: Macrophages (RAW 264.7) were treated with non‐toxic concentrations of either GSE or commercial polyphenols (gallic acid [GA] and [−]‐epigallocatechin‐3‐gallate [EGCG]) and stimulated with LPS of Actinobacillus actinomycetemcomitans or Fusobacterium nucleatum, and iNOS expression was evaluated by immunoblotting. Nitric oxide (NO) production was quantified using the colorimetric Griess assay, whereas ROS production was measured with the fluorescent 123‐dihydrorhodamine dye.Results: GSE strongly decreased NO and ROS production and iNOS expression by LPS‐stimulated macrophages. GA also revealed a strong inhibitory effect on NO production without affecting iNOS expression but slightly increasing ROS production. EGCG showed an inhibitory effect on NO and ROS production and on iNOS expression by macrophages.Conclusion: Our findings demonstrate that proanthocyanidins have potent antioxidant properties and should be considered a potential agent in the prevention of periodontal diseases.

Alginate/gelatin (Alg-Gel) hydrogels have been used experimentally, associated with mesenchymal stromal/stem cells (MSCs), to guide bone tissue formation. One of the main challenges for clinical application is optimizing Alg-Gel stiffness to guide osteogenesis. In this study, we investigated how Alg-Gel stiffness could modulate the dental pulp stem cell (DPSC) attachment, morphology, proliferation, and osteogenic differentiation, identifying the optimal conditions to uncouple osteogenesis from the other cell behaviors. An array of Alg-Gel hydrogels was prepared by casting different percentages of alginate and gelatin cross-linked with 2% CaCl₂. We have selected two hydrogels: one with a stiffness of 11 ± 1 kPa, referred to as “low-stiffness hydrogel”, formed by 2% alginate and 8% gelatin, and the other with a stiffness of 55 ± 3 kPa, referred to as “high-stiffness hydrogel”, formed by 8% alginate and 12% gelatin. Hydrogel analyses showed that the average swelling rates were 20 ± 3% for the low-stiffness hydrogels and 35 ± 2% for the high-stiffness hydrogels. The degradation percentage was 47 ± 5% and 18 ± 2% for the low- and high-stiffness hydrogels, respectively. Both hydrogel types showed homogeneous surface shape and protein (Alg-Gel) interaction with CaCl₂ as assessed by physicochemical characterization. Cell culture showed good adhesion of the DPSCs to the hydrogels and proliferation. Furthermore, better osteogenic activity, determined by ALP activity and ARS staining, was obtained with high-stiffness hydrogels (8% alginate and 12% gelatin). In summary, this study confirms the possibility of characterizing and optimizing the stiffness of Alg-Gel gel to guide osteogenesis in vitro without altering the other cellular properties of DPSCs.

Vascular disruption and bleeding during periodontitis likely increase the levels of hemoglobin in gingival crevicular fluid. The aim of this study was to investigate the effect of hemoglobin on the inflammatory responses of human macrophages stimulated with lipopolysaccharides (LPS) isolated from periodontopathogens. The production of interleukin-1 beta (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) by macrophages following challenges with Porphyromonas gingivalis and Fusobacterium nucleatum LPS in the presence or absence of human hemoglobin was analyzed by ELISA. The effect of hemoglobin on LPS-binding to macrophages was evaluated with ³H-LPS. Hemoglobin and LPS from periodontopathogens acted in synergy to stimulate the production of high levels of IL-1β, IL-6, IL-8, and TNF-α by macrophages. Hemoglobin also enhanced LPS-binding to macrophages. This study suggests that hemoglobin contributes to increases in the levels of pro-inflammatory mediators in periodontal sites by acting in synergy with LPS from periodontopathogens, thus favoring the progression of periodontitis.

Background: There is growing literature on the potential of digital technologies for improving access to, ensuring continuity and quality of health care, and to strengthen health systems. Some studies have reported the cost-effectiveness of teledentistry, its reliability for remote dental screening, diagnosis, consultation, and treatment planning. Nonetheless, current evidence suggests that teledentistry implementation faces many challenges and is not yet adopted by dental health care providers (DHCPs). Developing strategies to improve teledentistry adoption requires an understanding of the factors that promote or hinder its successful implementation. Objective: This systematic review aims to identify and synthetize barriers and enablers to implementing teledentistry as perceived by DHCPs in their clinical practices, using the Theoretical Domains Framework (TDF) and the Capacity, Opportunity, and Motivation Behavior (COM-B) model. Methods: This protocol follows the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Protocols) checklist. Literature will be searched in the following databases: PubMed, Cochrane Library, Web of Science, CINAHL, Embase, and PsycINFO. We will perform additional searches on Google, Google Scholar, and ProQuest Dissertations & Theses Global, screen the references of the included studies to capture additional relevant studies, and contact the authors of studies if we need more details. We will consider studies using qualitative, quantitative, and mixed methods. There will be no restrictions on the publication date and dental setting. We will include studies published in French, English, and Portuguese. Two independent reviewers will select the study, extract data, and assess methodological quality using the Mixed Methods Appraisal Tool’s checklist. Data analysis will include a descriptive and a thematic content analysis. We will synthetize and categorize the barriers and enablers using the TDF and COM-B model and present a narrative synthesis of our results using tables, figures, and quotes. Results: By March 2023, the literature search has retrieved 7355 publications. We will identify the range of barriers and enablers to implementing teledentistry through DHCPs’ perspectives. Considering the critical need for theory-based implementation interventions to improve the use of evidence-informed practices, we will synthesize the factors influencing the adoption of teledentistry based on the TDF domains and the 3 essential conditions predicting behavior change in accordance with the COM-B model. As needed, we will include additional determinants if not included in the TDF. We will conduct some subgroups analyses if studies are sufficient. We expect to complete the review by July 2024. Conclusions: This review will provide some insights on the determinants of teledentistry implementation as perceived by DHCPs in dental settings. These findings will cater to patients, families, DHCPs, researchers, academic and professional decision-makers, and policy makers. The results of the systematic review could be used to develop theory-led interventions in improving teledentistry implementation. Trial Registration: PROSPERO CRD42021293376; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=293376 International Registered Report Identifier (IRRID): PRR1-10.2196/44218

Alginate-gelatin (Alg-Gel) hydrogels have been used experimentally but not clinically associated with mesenchymal stromal / stem cells (MSCs) to guide bone tissue formation. One of the main challenges for its clinical application is optimizing Alg-Gel stiffness to guide osteogenesis. In this study, we investigated how Alg-Gel stiffness could modulate the dental pulp stem cell (DPSCs) attachment, morphology, proliferation, and osteogenic differentiation, identifying the optimal condition to uncouple osteogenesis from the other cell behaviors. An array of Alg-Gel hydrogels was prepared by casting different percentages of Alg and Gel being crosslinked with 2 % CaCl2. We selected two hydrogels, one with 11± 1 kPa called “low” stiffness and one with 55 ± 3 kPa called “high” stiffness. Hydrogel analyses showed that the average swelling rates were 20 ± 3% for low and 35 ± 2% for high hydrogels. The degradation percentage was 47 ± 5% and 18 ± 2% for low and high hydrogels, respectively. Both hydrogel types showed homogeneous surface shape and pro-tein (Alg-Gel) interaction with CaCl2 as assessed by FTIR-ATR and XPS. Cell culture showed good adhesion of the DPSCs to the hydrogels and proliferation. Furthermore, better osteogenic activity was obtained with high-stiffness hydrogels. In summary, this study confirms the possibility of characterizing and optimizing the stiffness of alginate-gelatin gel to guide osteogenesis in vitro without altering other cellular properties of DPSCs.