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Peri-implantitis associated with dental implants shares characteristics with destructive periodontal diseases. Both conditions are multifactorial and strongly correlated with the presence of microorganisms surrounding the prostheses or natural dentition. This study aimed to evaluate the antimicrobial activity and toxicity of a mucoadhesive hydrogel functionalized with aminochalcone (HAM-15) against Aggregatibacter actinomycetemcomitans, Fusobacterium periodonticum, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Candida albicans. Various experiments were conducted to determine the minimum inhibitory concentrations (MIC) and minimum bactericidal/fungicidal concentrations (MBC/MFC), as well as the antibiofilm potential and toxicity in human gingival fibroblasts and a G. mellonella animal model. Infection and treatment studies were also performed in G. mellonella. The results demonstrated that both aminochalcone (AM-15) and the aminochalcone-functionalized hydrogel (HAM-15) exhibited antimicrobial activity, with MICs ranging from 7.8 to 31.2 μg/mL for the tested strains. Treatment with HAM-15 at 300 μg/mL reduced the monospecies biofilm of C. albicans and P. gingivalis by 7 log 10 and 6 log 10 , respectively, and the mixed-species biofilm of these microorganisms by 7 log 10 and 8 log 10 , respectively. Regarding toxicity, HAM-15 showed cytotoxic effects on human gingival fibroblasts at high concentrations, but in the G. mellonella model, survival was 70 % at a dose of 1 mg/mL. Additionally, AM-15, when administered after larval infection, protected 90 % of the animals (p < 0.05). These results suggest that AM-15 is a promising candidate for the prevention and treatment of anaerobic infections and yeasts, demonstrating significant antimicrobial efficacy and an acceptable safety profile in experimental models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: This research assessed the potential role of okra (Abelmoschus esculentus L.) extract on periodontal tissue wound healing by evaluating its effects on human periodontal ligament fibroblast (hPDLF), human gingival fibroblast (hGF), and human osteoblast (hOB) cells in vitro., Methods: The viability effect of okra extract on hPDLF, hGF, and hOB cells was determined using the MTT assay protocol. The highest viability concentrations were applied to hPDLF and hOB cells, and the expression levels of on type 1 collagen (COL1), bone morphogenetic protein 2 (BMP2), axis inhibition protein 2 (AXIN2), and fibroblast growth factor 2 (FGF2) proteins were determined through ELISA. The extract was also tested for antioxidant (CUPRAC, DPPH, FCR, and FRAP tests), acetylcholinesterase (AChE) inhibition, and antimicrobial properties, and its content was determined by HPLC-DAD., Results: The viability results showed no significant difference between the okra extract-treated and control groups for all cell types. In hPDLF cells, higher expression levels of COL1 and AXIN2 in the okra extract-treated group compared to the control group, while BMP2 expression level was lower. In hOB cells, the extract-treated group had higher levels of COL1, BMP2, and AXIN2 expression than the control group., Conclusion: It can be posited that okra extract may activate the Wnt/β-catenin signalling pathway and may have a beneficial impact on wound healing in periodontal tissues. However, extensive long-term in-vivo research on the activation of signalling pathways by okra extract in periodontal wound healing is required., Competing Interests: Declarations. Human ethics and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Chronic inflammation of the tissues surrounding and supporting the teeth is known as periodontal disease. Human gingival fibroblasts (HGFs) are among the greatest prevalent cells in gingival tissue and play a crucial role in oral infections. Data from the GSE dataset revealed that the inflammatory cytokines IL-1β, IL-6, and IL-8 were up-regulated in periodontitis patients compared to healthy individuals. Betulin, a lupane-type pentacyclic triterpene alcohol extracted from the birch trees, inhibits lipopolysaccharide (LPS; component of gram-negative bacteria)-induced synthesis of IL-1β, IL-6, and IL-8 in HGFs. We also demonstrated that the MAPK and AP-1 signaling cascades mediate betulin's inhibition of inflammatory cytokine production in HGFs. Importantly, betulin reduces the expression of inflammatory cytokines and prevents the progression of ligature-induced periodontitis in vivo. This study provides evidence that betulin is a promising candidate for the management of periodontal disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Statement of Problem: High-translucency zirconia and lithium disilicate are among the most used materials in contemporary fixed prosthodontics because of their excellent esthetic and mechanical properties. However, their different cementation techniques, physical properties, and biocompatibility profiles can influence the clinician's choice., Purpose: The purpose of this in vitro study was to evaluate the mechanical strength and adhesive cementation techniques for zirconia and lithium disilicate materials through mechanical testing, including compressive and pull-out tests. The biocompatibility of these materials was also assessed., Material and Methods: A total of 72 human maxillary molars that were free from damage were embedded in acrylic resin and prepared 1 mm occlusal to the enamel-cementum junction. The specimens were divided into 3 groups: lithium disilicate (CAD), zirconia High-Translucency HT (CAD), and lithium disilicate (PRESS). Following the recommended cementation protocols, compression and pull-out tests were performed. Twelve disks of each group were fabricated to test the integration of gingival fibroblasts. Human gingival fibroblasts were isolated from gingival biopsies and cultured in Dulbecco modified Eagle medium (DMEM). Cell viability was determined using the 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, serving as an indicator of cellular respiration., Results: Zirconia was the most mechanically efficient material, with a high resistance value (2081.4 ±405.4 N). The pull-out test determined that CAD-CAM lithium disilicate had similar adhesive cementation strength (244.3 ±29.3 N) to the other groups. In terms of biocompatibility, all materials demonstrated good results, with lithium disilicate CAD emerging as the most biocompatible material. Statistically significant differences were observed between the zirconia HT material and lithium disilicate PRESS (P=.006) and between lithium disilicate CAD and lithium disilicate PRESS (P=.002)., Conclusions: All the monolithic restorations analyzed have shown excellent results in terms of mechanical properties, adhesion, and biocompatibility. Zirconia exhibited outstanding mechanical properties, making it an ideal choice for applications requiring high strength. To achieve adhesion results comparable with those of lithium disilicate, a protocol using airborne-particle abrasion and silane with 10-MDP is recommended. This approach ensures optimal adhesion, enhancing the longevity and effectiveness of the restoration., (Copyright © 2025 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the in vitro effects of minocycline on human gingival fibroblasts (HGFs), its clinical impact on early wound healing after implant placement, and its potential mechanism of action., Methods: First, we evaluated the in vitro proliferation, migration, and collagen production of HGFs treated with different concentrations of minocycline, as well as the underlying mechanism. Subsequently, we conducted a clinical trial and randomly assigned 40 partially edentulous patients to either the test (minocycline hydrochloride treatment) or control (blank control) group immediately after implant surgery. The early wound healing score (EHS), pain index, gingival index (GI), modified sulcus bleeding index (mSBI), and peri-implant crevicular fluid samples were assessed or collected 3 and/or 7 days after surgery., Results: In vitro, 1 μg/mL minocycline promoted the proliferation, migration, and collagen production of HGFs. Minocycline inhibited collagen degradation by downregulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-14 and upregulating tissue inhibitors of metalloproteinases-2. However, higher concentrations of minocycline, 10 and 100 μg/mL, exhibited adverse effects. In the randomised clinical trial, the test group showed significantly better clinical outcomes compared to the control group, with higher EHS and lower GI, mSBI, concentrations of IL-1β, IL-10, and TNF-α, and relative abundance of Streptococcus and gram-negative anaerobic bacteria., Conclusions: Small doses of minocycline (1 μg/mL) promoted the proliferation and migration of HGFs and inhibited collagen degradation in vitro. Locally delivered minocycline after implant surgery improves clinical outcomes by promoting early wound healing, relieving the inflammatory response, and decreasing early colonisation of gram-negative anaerobic bacteria., Trial Registration: This clinical trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100044680)., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The objective of this study is to investigate the effect of collagen matrix with polydeoxyribonucleotide (PDRN) at two concentrations on keratinized tissue (KT) regeneration for buccally positioned implants in canines., Methods: Four implants were placed in the edentulous mandible of five dogs simultaneously with KT removal. The implants were positioned buccally with respect to the ridge crest. After 2 months, KT augmentation was performed applying the following treatment modalities:(1) free gingival graft (FGG), (2) xenogeneic collagen matrix (XCM), (3) XCM loaded with 2 mg/mL PDRN (PDRN2), and (4) XCM loaded with 4 mg/mL PDRN (PDRN4). All animals were sacrificed 3 months later. Outcomes included clinical (KT height) and histomorphometric measurements (KT height/length, level of the mucosa, mucosal thickness, supracrestal soft tissue height)., Results: Clinical and histomorphometric KT formation at 3 months was greatest in groups with FGG (4.70 ± 1.00/3.94 ± 0.93 mm) and PDRN2 (4.85 ± 1.43/3.95 ± 0.87 mm). Group PDRN2 (1.87 ± 1.50 mm) showed a higher marginal mucosal level with respect to the implant platform compared to other groups (range: 0.57 ± 0.97-0.69 ± 1.14 mm). All groups presented a soft tissue thickness of < 2 mm on the buccal aspect of the implants., Conclusions: Based on the limitations of this pilot preclinical study, XCM with 2 mg/mL of PDRN demonstrated a potential for KT augmentation., (© 2024 The Author(s). Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)

Objective: This study investigated the use of oral rinse solutions formulated with boron-containing compounds, known for their antibacterial activity, as an alternative to chlorhexidine (CHX)., Material and Method: Boron nitride (BN), boric acid (BA) and sodium borate (SB) were used in the study. BN was used in nanosuspension (BN-NS) due to its low solubility in water. BA and SB were also prepared and used in solution form (BA-S, SB-S). Antibacterial activity against cariogenic bacteria was evaluated using agar well diffusion and microdilution techniques, and antibiofilm activity was evaluated using the crystal violet method. Cytotoxicity in human gingival cell lines (HGF-1) was evaluated using MTT and LDH assays. Surface hardness was measured with Vicker's Microhardness tester and surface roughness was measured with a profilometer. CHX was used as the control group., Results: BN-NS, BA-S, and SB-S showed antibacterial and antibiofilm activity against all cariogenic bacteria. BN-NS and SB-S demonstrated much lower cytotoxicity compared to CHX, while BA-S exhibited similar cytotoxicity. SB-S caused an increase in enamel surface hardness (p = 0.017), whereas no significant changes were observed in surface roughness or hardness in the other groups (p > 0.05)., Conclusion: BN-NS and SB-S showed antibacterial effects and antibiofilm activity on all tested cariogenic bacteria. BN-NS and SB-S showed lower cytotoxicity than CHX, and their effects on enamel and composite resin surfaces were similar to the control group. Further studies are needed to support the use of BN-NS and SB-S as alternatives to CHX., Clinical Revelance: BN-NS and SB-S are promising alternatives to the antibacterial agent CHX, which is known to be cytotoxic., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Atatürk University Faculty of Dentistry Ethics Committee (decision no. 22, dated 16.03.2021). Informed consent: Extracted human teeth were used in the study. Informed consent was obtained from the patients before tooth extraction., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to determine the cytotoxicity (irritant potency) of toothpaste ingredients, of which some had known to have sensitizing properties., Materials: From the wide variety of toothpaste ingredients, Xylitol, Propylene glycol (PEG), Sodium metaphosphate (SMP), Lemon, Peppermint, Fluoride, Cinnamon, and Triclosan and Sodium dodecyl sulphate (SDS) have been selected for evaluation of their cytotoxic properties., Methods: Reconstructed human gingiva (RHG) were topically exposed to toothpaste ingredients at different concentrations. The compound concentration resulting in 50% cell death (EC50) and 10% cell death (EC10) was determined by the MTT assay. Detrimental effects in tissue histology were observed by hematoxylin & eosin staining of tissue sections followed by microscopy., Results: While Xylitol, PEG, and SMP did not appear to affect cell viability or tissue histology, the concentrations of Lemon, Peppermint, Cinnamon and SDS present in toothpastes exceeded the EC50 value and resulted in clear detrimental effects in tissue histology, indicating that they could harm the oral mucosa. Triclosan and Fluoride concentrations in the tested toothpastes exceeded the EC10 value but remained below the EC50 value with no clear detrimental effects in tissue histology., Clinical Significance: Manufacturers are encouraged to comply with higher standards of quality and safety for toothpaste., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Kasi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This investigation sought to evaluate cytotoxic and genotoxic effects of two different types of orthodontic bands after aging in acidic and neutral artificial saliva using human gingival fibroblast-like (HGF1-PI 1) cell lines., Methods: Two commercial brands of orthodontic molar bands (American orthodontic (AO) and 3 S-dental bands), commonly used by orthodontists, were tested. These bands were divided into four groups to examine the effects of aging following thermocycling, and pH variations (pH = 4.5 and pH = 7.4). Cytotoxicity was assessed using the MTT assay. Comet assay was used to evaluate genotoxicity., Results: Our results demonstrated that AO molar bands exhibited significant cytotoxic effect on gingiva cells following incubation in acidic condition compared to untreated control (P = 0.04), however no effect was observed at neutral condition. In contrast, 3 S-dental molar bands showed no significant differences at both conditions compared to control group. Regarding genotoxicity, DNA damage was evident for both brands at pH = 4.5, however, AO molar bands demonstrated longer comet tails compared to 3 S-dental molar bands. AO molar bands was also showed relatively DNA destruction at pH 7.4, while no genotoxicity was for 3 S-dental molar bands., Conclusion: The results collectively showed that AO molar bands exhibited cytotoxicity only at acidic pH, while 3 S-dental molar bands showed no cytotoxic effects at either acidic or neutral conditions. Additionally, AO molar bands demonstrated greater genotoxicity than 3 S-dental molar bands at both pH levels. These data represented acceptable biocompatibility for both bands in neutral conditions. However, AO bands seem to become toxic for gingiva cells in acidic milieu., Competing Interests: Declarations. Ethics approval and consent to participate: The Current study was approved by the Ethics Committee of the Vice Chancellor for Research, Shiraz University of Medical Sciences Ethics Code (IR.SUMS.DENTAL.REC. 1398.137). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Three dimensional (3D) printing materials are widely used in dental applications, but their biocompatibility and interactions with human cells require evaluation. This study aimed to identify materials meeting biocompatibility, mechanical strength, and tissue-forming requirements for safe dental applications. We assessed the cytotoxicity of resins and thermoplastic filaments in human HaCaT keratinocytes, gingival fibroblasts (hGFs), and stem cells from human exfoliated deciduous teeth (SHED) using PrestoBlue assays. Three resins, including two types of surgical guide resins, exhibited strong cytotoxicity after 4-72 h, while 2 h exposure to an FDA-approved surgical guide resin did not affect SHED cell viability. In contrast, six thermoplastic filaments showed no significant cytotoxicity even after 72 h. Among these, polycarbonate-acrylonitrile butadiene styrene (PC-ABS) demonstrated excellent toughness, heat resistance, and surface quality at a low cost. SHED cells cultured on PC-ABS dishes and micro bone structures showed strong proliferation and osteogenic potential. Culture inserts made of PC-ABS also supported the growth of HaCaT keratinocytes and the hGFs formed gingival tissue, which was superior to that formed on commercially available PET inserts. In conclusion, PC-ABS is a promising 3D printing material for dental applications due to its biocompatibility, ability to promote osteogenesis, and support for gingival tissue formation, with no observed cytotoxicity.

Hyaluronic acid (HA) has received considerable attention in the reconstruction of lost periodontal tissues. HA has been proposed to play a role in cell proliferation, differentiation, migration, and cell-matrix as well as cell-cell interactions. Although various studies have been conducted, further research is needed to expand our knowledge based on HA such as its effects on cell proliferation and osteogenic differentiation. The aim of this study is to assess, in single- and multi-culture plate models, the effect of HA on the proliferation, viability, and function of periodontal ligament fibroblasts, osteoblasts, and gingival epithelial cells. A novel multi-culture cell plate was chosen to simulate a cell-cell communication as close as possible to a real clinical condition in an in vitro setting. We found that HA exclusively enhanced epithelial cell proliferation, while intercellular communication stimulated the proliferation and osteogenic potential of the osteoblasts, independently from HA use. The proliferation and function of the periodontal ligament fibroblasts were not changed by HA or the cellular interplay. The use of multi-culture plates could represent a promising method to investigate and compare dental biomaterials in experiments mimicking an in vivo environment.

Background and Objectives: Insulin-like growth factor-1 (IGF-1) plays a vital role in various cellular processes, including those involving stem cells. This study evaluated the effects of IGF-1 on cell survival, osteogenic differentiation, and mRNA expression in gingiva-derived mesenchymal stem cell spheroids. Materials and Methods: Using concave microwells, spheroids were generated in the presence of IGF-1 at concentrations of 0, 10, and 100 ng/mL. Cellular vitality was qualitatively assessed using microscopy, while a water-soluble tetrazolium salt-based assay kit quantified cellular viability. Osteogenic differentiation was evaluated via alkaline phosphatase activity and an anthraquinone dye test to measure calcium deposition. Additionally, quantitative polymerase chain reaction (qPCR) analysis was performed to determine the expression of RUNX2 and COL1A1. Results: By day 1, the stem cell spheroids had successfully formed, and their morphology remained stable over the following 7 days. The IGF-1 concentrations tested showed no significant differences in cell viability. Similarly, alkaline phosphatase activity on day 7 revealed no observable changes. However, on day 7, the incorporation of IGF-1 led to an increase in Alizarin Red staining, indicative of enhanced calcium deposition. Notably, an IGF-1 concentration of 100 ng/mL significantly upregulated the expression of COL1A1. Conclusions: These findings suggest that IGF-1 supports the maintenance of cell viability and promotes the expression of COL1A1 in gingiva-derived mesenchymal stem cell spheroids, highlighting its potential role in enhancing osteogenic differentiation. Future research should include long-term studies to evaluate the sustainability of IGF-1-induced effects on stem cell spheroids.

The present systematic review (SR) aims to evaluate manuscripts in order to help further elucidate the following question: is the micronucleus assay (MA) also a useful marker in gingiva, tongue, and palate for evaluating cytogenetic damage in vivo? A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to December 2023. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CIs) were established. Full manuscripts from 34 studies were carefully selected and reviewed in this setting. Our results demonstrate that the MA may be a useful biomarker of gingival tissue damage in vivo, and this tissue could be a useful alternative to the buccal mucosa. The meta-analysis analyzing the different sites regardless of the deleterious factor studied, the buccal mucosa (SMD = 0.69, 95% CI, - 0.49 to 1.88, p = 0.25) and gingiva (SMD = 0.31, 95% CI, - 0.11 to 0.72, p = 0.15), showed similar results and different outcome for the tongue (SMD = 1.19, 95% CI, 0.47 to 1.91, p = 0.001). In summary, our conclusion suggests that the MA can be a useful marker for detecting DNA damage in gingiva in vivo and that this tissue could be effective site for smearing., (© 2024 John Wiley & Sons Ltd.)

Background: This study aimed at comparing gingival depigmentation by locally injected vitamin C with surgical depigmentation, in terms of effectiveness and patient acceptability. Methods: Forty-two patients presenting with ethnicity-related hyperpigmentation were randomly divided into two groups, Group I ( n  = 21) was treated with locally injected vitamin C and Group II ( n  = 21) was treated by surgical depigmentation. The outcome was assessed using Gingival Pigmentation Index (GPI) and Skin Hyperpigmentation Index (SHI). Results: Both the techniques were successful in treating gingival hyperpigmentation, but the patients who underwent vitamin C-based depigmentation showed significantly higher satisfaction with the treatment result, based on patient reported Visual Analog Scale (VAS) scoring. Conclusion: Based on the findings of this study, it was concluded that locally injected vitamin C and surgical depigmentation are comparable in their effectiveness for treating gingival hyperpigmentation. Trial Registration: ClinicalTrials.gov identifier: CTRI/2023/02/050127., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Aehad Ul Haque et al.)

Background and Objectives : Vascular endothelial growth factor (VEGF) is a protein which stimulates the formation of new blood vessels, playing a crucial role in processes such as wound healing and tumor growth. Methods : This study investigated the effects of VEGF on cell viability and osteogenic differentiation in mesenchymal stem cell (MSC) spheroids. Stem cell spheroids were fabricated using concave microwells and cultured with VEGF at concentrations of 0, 0.01, 0.1, 1, and 10 ng/mL. Morphological assessments were conducted on days 1, 3, 5, and 7, while cell viability was evaluated using the LIVE/DEAD assay and Cell Counting Kit-8. Alkaline phosphatase activity (ALP) and calcium deposition were measured to assess osteogenic differentiation, and qPCR was used to analyze osteogenic marker expression. Results : The spheroids maintained their shape across all VEGF concentrations, with the largest diameter being at 0.01 ng/mL on day 1, which decreased over time. Cell viability was highest at 0.01 ng/mL VEGF, while calcium deposition peaked at 0.1 ng/mL. Osteogenic markers, including RUNX2, osteocalcin, and COL1A1, showed significant upregulation at 1 ng/mL VEGF. Conclusions : These results suggest that VEGF enhances early osteogenic differentiation in MSC spheroids, indicating its potential for bone repair and tissue regeneration. VEGF could be applied in clinical settings for bone healing, fracture repair, and regenerative dentistry treatments.

Gingival overgrowth caused by cyclosporine A is due to increased fibroblast proliferation in gingival tissues. Cell cycle system balances proliferation and anti-proliferation of gingival fibroblasts and plays a role in the maintenance of its population in gingival tissues. When cells detect and respond to abnormalities (e.g. DNA damage), cell cycle progression is arrested in the G1 phase until the completion of damage restoration. In this study, we investigated the effects of cyclosporine A on G1 cell cycle arrest and on its regulators in gingival fibroblasts to clarify the mechanism of cyclosporine A-induced gingival overgrowth. Human gingival fibroblasts from healthy donors were cultured to semi-confluence and were then treated with or without 200 ng/mL (166 nM) cyclosporine A in D-MEM with 2% fetal bovine serum. Cell proliferation was assessed by counting total cell numbers. The distribution of cell cycle phases was assessed using flow cytometric analysis. The levels of mRNA and protein expression for cell cycle regulators were quantified using reverse transcription-quantitative PCR and western blot analysis, respectively. Treatment with cyclosporine A markedly increased cell proliferation, inhibited G1 cell cycle arrest, significantly increased CDC25A and CYCLIN E1 mRNA expression levels, significantly decreased P21, SMAD3 and SMAD4 mRNA expression levels, significantly upregulated the protein expression levels of CDC25A, CYCLIN E1, pCDK2 and pRB1 and significantly downregulated the protein expression levels of P21, SMAD3 and SMAD4. Treatment with cyclosporine A also increased MYC and ATM mRNA expression levels and decreased CDK2, ATR, P27, P53 and RB1 mRNA expression levels but not significantly. These results demonstrate that cyclosporine A causes gingival overgrowth due to the following mechanism in gingival fibroblasts: cyclosporine A increases levels of phospho-CDK2 and CYCLIN E1 by upregulating CDC25A and downregulating P21 with the downregulation of SMAD3 and SMAD4, which results in the inhibition of G1 cell cycle arrest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Takeuchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite the significant recent advances in manufacturing materials supporting advanced dental therapies, peri-implantitis still represents a severe complication in dental implantology. Herein, a sol-gel process is proposed to easily deposit antibacterial zirconia coatings onto bulk zirconia, material, which is becoming very popular for the manufacturing of abutments. The coatings' physicochemical properties were analyzed through x-ray diffraction and scanning electron microscopy-energy-dispersive x-ray spectroscopy investigations, while their stability and wettability were assessed by microscratch testing and static contact angle measurements. Uniform gallium-doped tetragonal zirconia coatings were obtained, featuring optimal mechanical stability and a hydrophilic behavior. The biological investigations pointed out that gallium-doped zirconia coatings: (i) displayed full cytocompatibility toward human gingival fibroblasts; (ii) exhibited significant antimicrobial activity against the Aggregatibacter actinomycetemcomitans pathogen; (iii) were able to preserve the commensal Streptococcus salivarius. Furthermore, the proteomic analyses revealed that the presence of Ga did not impair the normal oral microbiota. Still, interestingly, it decreased by 17% the presence of Fusobacterium nucleatum, a gram-negative, strictly anaerobic bacteria that is naturally present in the gastrointestinal tract. Therefore, this work can provide a valuable starting point for the development of coatings aimed at easily improving zirconia dental implants' performance., (© 2024 Wiley Periodicals LLC.)

Objectives: This study evaluates the efficacy of polyvinylpyrrolidone-sodium hyaluronate (PVP-SH) gel as a dressing material in enhancing both clinical and patient-reported outcomes post-free gingival graft (FGG) harvesting from the hard palate., Material and Methods: This randomized clinical trial included 18 patients and spanned from June 2022 to August 2023. Patients received an FGG procedure to manage a lack of attached gingiva. Following graft harvesting, patients were divided into two groups: the control group, which received Coe-Pak, and the test group, which was treated with PVP-SH gel. The primary outcome measured was complete epithelialization. Secondary outcomes included the Landry healing scale, post-operative pain level, and patient willingness to receive the same treatment again., Results: The test group reported significantly lower analgesic use (p < 0.001) and reduced pain severity (p < 0.001) compared to the control group. Furthermore, test group patients indicated a higher level of satisfaction regarding the prospect of retreatment. In contrast, the control group showed significantly slower progress in wound healing and epithelization (p < 0.05) compared to the test group., Conclusions: The findings of this study suggest that PVP-SH gel is a superior dressing material post-FGG harvesting, yielding improved clinical and patient-reported outcomes relative to Coe-Pak., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Approximately one in five individuals experience alveolar osteitis (AO) following wisdom tooth extraction. AO is characterised by loss of the blood clot from the tooth extraction socket leading to infection and pain, resulting in repeated hospital visits that impose a substantial burden on healthcare systems. Current treatments are sub-optimal; to address this we developed a novel drug-loaded mucoadhesive patch composed of dual electrospun polyvinyl pyrrolidone/Eudragit RS100 (PVP/RS100) and poly(N-isopropylacrylamide) (PNIPAM) fibres protected by a poly(ε-caprolactone) (PCL) backing layer. These patches demonstrated controlled release of the long-acting analgesic bupivacaine HCl and the anti-inflammatory drug prednisolone. Topical application of patches to tissue-engineered gingival mucosa showed that patch-released bupivacaine and prednisolone achieved sustained tissue permeation with 54.8 ± 3.3 % bupivacaine HCl and 65.8 ± 5.1 % prednisolone permeating the epithelium after 24 h. The drugs retained their functionality after release; bupivacaine HCl significantly (p < 0.05) inhibited veratridine-induced intracellular calcium flux in SH-SY5Y neuronal cells, while prednisolone significantly reduced gene expression of IL-6 (2-fold; p < 0.001), CXCL8 (5.1-fold; p < 0.01) and TNF-α (1.5-fold; p < 0.001) in stimulated THP-1 monocytes. Taken together, these data show that dual electrospun patches have the potential to provide a mucoadhesive covering to prevent blood clot loss while delivering pain relief and anti-inflammatory therapeutics at tooth extraction sites to prevent and treat AO. This study not only offers a future therapeutic pathway for AO but also contributes valuable insights into future advancements in drug delivery devices for periodontal or oral mucosal tissue., Competing Interests: Declaration of Competing Interest PVH is a scientific advisor to AFYX. CM, HEC, JGE, SGS have all previously received funding from AFYX, although AFYX did not fund any part of this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The biocompatibility of dental materials is critical for ensuring safety in clinical applications. However, standard in vitro cytotoxicity assays often rely on stiff tissue culture plastic (TCP), which does not accurately replicate the biomechanical properties of soft oral tissues. In this study, we compared human gingival fibroblasts (HGFs) cultured on soft, gel-based substrates mimicking gingival tissue stiffness (0.2 kPa) with those cultured on conventional TCP (3 GPa) to assess the influence of substrate stiffness on the cytotoxicity of methyl methacrylate (MMA), as well as other cytotoxic agents, including DMSO and H 2 O 2 . The results demonstrated that cells cultured on softer substrates exhibited enhanced resistance to cytotoxic stress, with increased viability and decreased apoptosis and DNA damage following exposure to MMA, DMSO, and H 2 O 2 . Notably, HGFs on soft substrates showed significantly greater resilience to MMA-induced cytotoxicity compared to those cultured on TCP. These findings emphasize the critical role of substrate stiffness in modulating cellular responses to toxic agents and highlight the necessity of using physiologically relevant models for cytotoxicity testing of dental materials. This study provides valuable insights for improving biocompatibility assessment protocols in clinical settings.

Background: This study investigates the dose-response relationship of acetylcholine (ACh) on healthy human gingival blood flow (GBF). Understanding this dose-response relationship contributes to studying vasodilatory mechanisms in various pathological conditions., Methods: The study involved 22 young healthy men (21 - 32 years) to investigate the dose-response relationship of ACh on GBF. Semi-circular wells were created on the labial surface of the upper right second incisor (FDI #12) and upper left first incisor (FDI #21), including the gingival sulcus, for the application of drugs. ACh-chloride solutions at 0.1, 1, and 10 mg/mL were administered to the gingival sulcus of tooth FDI #12 with a Hamilton syringe. Physiological saline was applied on the contralateral side to FDI #21 as a control. The GBF was measured non-invasively by the laser speckle contrast imaging method in four 1mm high adjacent regions: coronal, midway1, midway2, and apical, and was expressed in a laser speckle perfusion unit (LSPU). After the baseline blood flow recording, ACh doses were applied sequentially, with washout periods in between. Data were statistically analyzed using a linear mixed model., Results: The GBF did not change on the saline site throughout the experiment. The GBF was significantly higher at the coronal region after all ACh doses (baseline: 218±31 LSPU, and 227±38 LSPU p < 0.05, 239±40 LSPU p < 0.001, 291±54 LSPU p < 0.001, respectively) compared to the saline. It was also elevated following 1 and 10 mg/mL at the midway1 (245±48 LSPU, p < 0.05, 293±65 LSPU p < 0.001). At midway2 and apical, only the 10 mg/mL dose was effective (285±71 LSPU, p < 0.001; 302±82 LSPU, p < 0.001)., Conclusions: Our findings suggest a dose-dependent vasodilation to ACh, emphasizing its role in human gingival microcirculation. Only the 10 mg/mL ACh could evoke remote vasodilation 3 mm from the application. The described method could facilitate the investigation of endothelium-dependent vasodilation in disorders affecting microcirculation, such as periodontitis or diabetes., Competing Interests: Declarations Ethics approval and consent to participate Informed consent to participate was obtained from all of the participants in the study. The investigation adhered to the principles outlined in the Declaration of Helsinki. The investigation received ethical approval from the Medical Scientific Council, a specialist authority ethical committee for the Hungarian National Public Health and Medical Officer Service (57734-7/2022/EÜIG). Each participant received written information detailing the measurement process and any potential risks. Consent for publication All participants agreed to the publication of non-identifiable photographs in an open-access journal. The publication does not include any images that could enable the identification of individual participants. The participants have obtained informed consent for the publication of their data. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: The objectives of this study were to develop a tooth-binding graphene quantum dots silver nanocomposites (ALN-GQDs-Ag) and evaluate their antibacterial, mineralising, and discolouring properties for the prevention of dental caries., Methods: In this study, ALN-GQDs-Ag were developed by synthesising nano silver (Ag) with graphene quantum dots (GQDs) and functionalised GQDs with alendronate (ALN). ALN-GQDs-Ag were characterised by transmission electron microscopy (TEM), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. The cytotoxicity of ALN-GQDs-Ag against human gingival fibroblasts (HGF-1) and stem cells from human exfoliated deciduous teeth (SHED) was examined using a colorimetric assay with reference to silver nitrate solution. The affinity of ALN-GQDs-Ag for hydroxyapatite particles was investigated using inductively coupled plasma spectroscopy (ICP). The antibacterial properties of ALN-GQDs-Ag against Streptococcus mutans were evaluated by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and colony-forming units counting (CFUs). The mineralisation properties of ALN-GQDs-Ag on human dentine were assessed using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), and Fourier transform infrared in a biochemical cycling model. The discolouring properties of ALN-GQDs-Ag on artificial dentine caries were determined using spectrophotometry., Results: TEM, Zeta potential, XPS, FTIR, and Raman spectroscopy confirmed the synthesis of stable spherical ALN-GQD-Ag nanocomposites with a 10.3 ± 5.5 nm diameter. The colorimetric assay demonstrated that ALN-GQDs-Ag were less cytotoxic than silver nitrate to HGF-1 and SHED (p<0.001). ICP showed that ALN-GQDs-Ag were bound to hydroxyapatite. SEM, CLSM, and CFUs showed that ALN-GQDs-Ag was bactericidal and inhibited biofilm growth of Streptococcus mutans . Micro-CT, SEM, and FTIR showed that ALN-GQDs-Ag repressed dentine demineralisation under a cariogenic challenge. Spectrophotometry revealed no significant discolouration of dentine caries in the ALN-GQDs-Ag., Conclusion: This study developed a biocompatible and tooth-binding ALN-GQDs-Ag with promising antibacterial, mineralising, and non-discolouring properties. ALN-GQDs-Ag could be a novel anti-caries agent for preventing dentine caries if translated for clinical use., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study., (© 2024 Yin et al.)

Drug-induced gingival enlargement (DIGE) is a side effect of ciclosporin, calcium channel blockers, and phenytoin. DIGE is a serious disease that leads to masticatory and esthetic disorders, severe caries, and periodontitis but currently has no standard treatment. We recently reported that nuclear receptor 4A1 (NR4A1) is a potential therapeutic target for DIGE. This study aimed to evaluate the therapeutic effects of n-butylidenephthalide (BP), which increases the expression of NR4A1, on DIGE. In this study, NR4A1 mRNA expression was analyzed in the patients with periodontal disease (PD) and DIGE. We evaluated the effect of BP on NR4A1 expression in gingival fibroblasts and in a DIGE mouse model. RNA sequencing (RNA-seq) was conducted to identify the mechanisms by which BP increases NR4A1 expression. The results showed that NR4A1 mRNA expression in the patients with DIGE was significantly lower than the patients with PD. BP suppressed the upregulation of COL1A1 expression, which was upregulated by TGF-β. BP also ameliorated gingival overgrowth in DIGE mice and reduced Col1a1 and Pai1 expression. BP also decreased Il1β mRNA expression in gingival tissue in DIGE. RNA-seq results showed an increase in the expression of several genes related to mitogen-activated protein kinase including DUSP genes in gingival fibroblasts stimulated by BP. Treatment with ERK and JNK inhibitors suppressed the BP-induced increase in NR4A1 expression. In addition, BP promoted the phosphorylation of ERK in gingival fibroblasts. In conclusion, BP increases NR4A1 expression in gingival fibroblasts through ERK and JNK signaling, demonstrating its potential as a preventive and therapeutic agent against DIGE., (© 2024 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Objective: To develop a novel and biocompatible copper tetraamine fluoride (CTF) with antibacterial and nondiscolouring properties., Method: This study used copper fluoride and ammonia solution to develop CTF solution. The CTF was characterized by X-ray photoelectron spectroscopy (XPS). Cytotoxicity was evaluated by stem cells from human exfoliated deciduous teeth (SHED) and human gingival fibroblasts (HGF-1). The fluoride concentration was determined using ion-selective electrode. The alkalinity was measured by a pH electrode. The human dentine blocks were treated with CTF and then incubated with Streptococcus mutans to evaluate the antimicrobial and discolouring effects. The silver diamine fluoride (SDF) was employed as the positive control, and water was the negative control. The colony-forming units (CFUs) and confocal laser scanning microscopy (CLSM) were used to examine the kinetics and viability of the biofilm. The discolouring property on dentine was assessed by spectrophotometry. One-way analysis of variance with the Bonferroni post hoc test was performed to assess and compare the data., Results: XPS confirmed synthesis of CTF solution. The half-maximal inhibitory concentration of CTF on SHED and HGF-1 was 195±16 ppm and 137±11 ppm. The fluoride concentration was 121,000±5,000 ppm. The pH value was 9. Log 10 CFU of the CTF, SDF and water group were 5.0 ± 0.2, 4.9 ± 0.1 and 7.4 ± 0.1 (p < 0.001, CTF, SDFWater). Spectrophotometry showed that the ΔE of the CTF, SDF and water group were 5 ± 2, 6 ± 3 and 45±2 (p < 0.001, CTF, Water

Objective: To assess the corrosion products and cytotoxicity of generic and proprietary fixed lingual retainers (FLRs)., Materials and Methods: Seven FLRs were investigated. Wires were submersed in solution for 34 days, at 37°C, under constant agitation. A proportion of this solution was analyzed to determine the concentration of metallic ions leaching off the wires. The remainder was diluted to 5%, 10% and 20% followed by exposure to human gingival fibroblasts and analysis of cytotoxicity of the wires., Results: Three wires (Dentaflex, Universal, and AZDent) released excessive concentrations of lead, two wires (MeshMark and Orthoflex) released excessive concentrations of nickel, and one wire (Universal) released excessive concentrations of molybdenum into solution. No statistically significant difference was found between the wires analyzed (P = .24). Slight cytotoxicity was noted in only one wire (Dentaflex) at a 20% dilution of eluent. This was also the wire which released the highest concentration of lead into solution. All other wires, at all concentrations, were deemed noncytotoxic, but five samples overall were deemed statistically significant (P < .0024). A statistically significant difference existed between wires (P = .013) and concentrations analyzed (P < .001)., Conclusions: Metals were released in differing quantities from all wires, with some elemental concentrations measuring more than that deemed acceptable in drinking water in Australia. A trend toward increased cell viability across samples was found with only one demonstrating cytotoxicity. There was no indication that generic FLRs were more or less biocompatible than their proprietary counterparts., (© 2024 by The EH Angle Education and Research Foundation, Inc.)

Background: Prolonged inflammation and oxidative stress can impede healing. To enhance healing efficiency, many solutions have been employed. This is an in vivo study comparing chlorhexidine (CHX) to a commercial antioxidant gel (AO)., Methods: Envelope flaps were created in the lower incisor gingival region of 60 Sprague-Dawley rats, and acellular dermal matrix (ADM) was inserted. Animals were randomly assigned to postsurgical treatment application of AO gel or 0.12% CHX twice daily. A control group received no postsurgical treatment. Data collected (before surgery, 24 h, and 72 h) included surgical images, tissue samples, and weights. Blinded scorers assessed images using a wound healing scale. Real-time polymerase chain reaction (RT-PCR) was used for gene expression of tumor necrosis factor-alpha (TNFα), interleukin-1 (IL-1), myeloperoxidase (MPO), and superoxide dismutase (SOD)., Results: The AO group scored higher than the CHX and control groups in clinical evaluation (p < 0.05). At 24 h, TNFα expression was upregulated in the AO group compared to CHX (p = 0.027) and controls (p = 0.018). The AO group had significantly higher expression of antioxidant enzyme (SOD) at 24 h compared to CHX (p = 0.021). All animals lost weight in the first 24 h. Animals treated with AO or CHX regained more weight at 72 h than control animals (p = 0.034 and 0.003, respectively)., Conclusion: Animals treated with AO healed faster. AO led to earlier upregulation of TNFα and antioxidant enzyme SOD. We hypothesized that AO promoted an earlier inflammatory process while counteracting oxidative stress by increasing antioxidant responses via SOD., (© 2024 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Periodontal disease (PD) prevention and treatment products typically demonstrate excellent antibacterial activity, but recent studies have raised concerns about their toxicity on oral tissues. Therefore, finding a biocompatible alternative that retains antimicrobial properties is imperative. In this study, a chemically modified hyaluronic acid (HA) hydrogel containing mangostanin (MGTN) was developed. Native HA was chemically modified, incorporating amino and aldehyde groups in different batches of HA, allowing spontaneous crosslinking and gelation when combined at room temperature. MGTN at different concentrations was incorporated before gelation. The structure, swelling characteristics MGTN release, rheological parameters, and in vitro degradation performance of the loaded hydrogel were first evaluated in the study. Then, antimicrobial properties were tested on Porphyromonas gingivalis and its biocompatibility in 3D-engineered human gingiva. HA hydrogel was very stable and showed a sustained release for MGTN for at least 7 days. MGTN-loaded HA hydrogel showed equivalent antimicrobial activity compared to a commercial gel of HA containing 0.2 % chlorhexidine (CHX). In contrast, while MGTN HA hydrogel was biocompatible, CHX gel showed high cytotoxicity, causing cell death and tissue damage. Modified HA hydrogel allows controlled release of MGTN, resulting in a highly biocompatible hydrogel with antibacterial properties. This hydrogel is a suitable alternative therapy to prevent and treat PD., Competing Interests: Declaration of competing interest The authors are inventors of a pending patent application based on some aspects of this work (WO2023180564A1)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate possible cytotoxic effects of thermoplastic materials commonly used for occlusal splints and orthodontic appliances., Methods: Seven thermoplastics were included: three variants of the Essix sheets (C+, Plus, and Tray Rite; Dentsply Sirona), three thermoplastics (Bleach Heavy, Splint, and X-Heavy; Cavex Holland) and Invisalign (Align Technology). Cylindrical specimens (n = 24; 10 mm diameter) were incubated in cell culture medium for 24 h and 14 days. After incubation, the medium was collected, serially diluted, and dosed to primary human gingival fibroblasts in triplicate. Medium processed like the samples was used as negative control. Cell viability was evaluated by XTT and LDH assay to assess metabolic activity and membrane integrity, respectively. Next, cell cycle was assessed with flow cytometry after exposing HGFs to undiluted extracts., Results: The 24-hour and 14-day extracts did not evoke cytotoxicity after 24-hour incubation. No significant differences in cell viability (one-way ANOVA, p > 0.05 ) in the XTT and LDH assays or in cell cycle distribution between the different materials (two-way ANOVA, p > 0.05 )., Conclusion: The thermoplastics tested in the study showed no evident in-vitro cytotoxic effects. Further investigation should focus on determining which compounds are released from thermoplastic materials and assessing potential toxicity related to exposure to these compounds., Clinical Significance: Our study adds to the growing body of evidence on the biocompatibility of dental thermoplastics. This can aid clinical decision-making, as thermoplastics are expected to be safe to use in terms of cytotoxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Self-adhesive resin cements (SARCs) are widely used for fixed prostheses, but incomplete cleaning near the gingival margin can cause inflammation. However, the factors influencing cement properties and the biological response of gingival fibroblasts to cement eluates are not well understood. This study examines the impact of two light-polymerizing units (LPUs) on the physical and chemical properties of two SARCs under simulated clinical conditions, as well as the subsequent response of human gingival fibroblasts (hGFs) to these eluates., Methods: Dental cement discs of SARCs were polymerized using Kerr DemiPlus and 3 M Elipar DeepCure-S LED LPUs with or without a 2-mm thick zirconia screen. Physical properties (microhardness, surface roughness, residual monomers) were evaluated. hGFs' cell viability, wound healing potency, and gene expression were assessed., Results: Both Maxcem and RelyX exhibited reduced microhardness and increased surface roughness when polymerized through zirconia or with DemiPlus LPU. Higher residual monomers (HEMA and GDMA in Maxcem; TEGDMA in RelyX) concentration was observed with DemiPlus and zirconia polymerization. Maxcem polymerized with DemiPlus exhibited lower cell viability, impaired healing, and altered gene expression in hGFs compared to those polymerized with Elipar LPU. Gene expression changes included downregulated NRF2 and HO-1 and upregulated CCR-3., Conclusions: Light-polymerizing Maxcem through zirconia with DemiPlus LPU compromised SARCs' properties, leading to higher residual monomers and negatively impacting hGFs' viability, healing, and gene expression. Careful material selection and polymerization techniques are crucial to minimize adverse effects on surrounding tissues., Clinical Significance: Clinicians should exercise caution when using LPUs and SARCs, especially when polymerizing through zirconia. This will help optimize the physical and chemical properties of SARCs and minimize potential adverse effects on the surrounding gingival soft tissues., (© 2024. The Author(s).)

Background: Commensal bacteria colonizing oral mucosa and skin play an essential role in maintaining host-microbiome homeostasis. It is unknown whether cytotoxicity resulting from metal ions leaching from medical devices may be influenced by commensal microbes., Objective: Determine whether the extent of apoptosis triggered by nickel or titanium ions is influenced by Streptococcus mitis and whether apoptosis occurs via the intrinsic or extrinsic apoptosis pathway., Methods: Reconstructed Human Gingiva (RHG) and Skin (RHS) were topically exposed to titanium or nickel salts in the presence or absence of S. mitis. Cytotoxicity and apoptosis were assessed by histology, immunohistochemistry, TUNEL assay, and Western Blot., Results: S. mitis alone resulted in negligible cytotoxicity. After metal exposure, localized apoptosis was observed in the epithelium and fibroblasts within the lamina propria hydrogel of both RHG and RHS. S. mitis enhanced metal-mediated apoptosis in gingiva but not in skin. Apoptosis was mediated via the extrinsic pathway caspase 8. Activation of the execution phase of apoptosis occurred via caspases 3 and 7, and PARP-1., Conclusion: Our study supports the finding that metals have irritant, cytotoxic properties resulting in apoptosis when leaching into skin or gingiva. Particularly for gingiva, commensal microbes exaggerate this detrimental effect., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic wounds significantly impact the patients' quality of life, creating an urgent interdisciplinary clinical challenge. The development of novel agents capable of accelerating the healing process is essential. Caffeic acid phenethyl ester (CAPE) has demonstrated positive effects on skin regeneration. However, its susceptibility to degradation limits its pharmaceutical application. Chemical modification of the structure improves the pharmacokinetics of this bioactive phenol. Hence, two novel series of CAPE hybrids were designed, synthesized, and investigated as potential skin regenerative agents. To enhance the stability and therapeutic efficacy, a caffeic acid frame was combined with quinolines or isoquinolines by an ester (1a-f) or an amide linkage (2a-f). The effects on cell viability of human gingival fibroblasts (HGFs) and HaCaT cells were evaluated at different concentrations; they are not cytotoxic, and some proved to stimulate cell proliferation. The most promising compounds underwent a wound-healing assay in HGFs and HaCaT at the lowest concentrations. Antimicrobial antioxidant properties were also explored. The chemical and thermal stabilities of the best compounds were assessed. In silico predictions were employed to anticipate skin penetration capabilities. Our findings highlight the therapeutic potential of caffeic acid phenethyl ester (CAPE) derivatives 1a and 1d as skin regenerative agents, being able to stimulate cell proliferation, control bacterial growth, regulate ROS levels, and being thermally and chemically stable. An interesting structure-activity relationship was discussed to suggest a promising multitargeted approach for enhanced wound healing., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

A novel gingival retraction cord named P/TA@CSy was prepared using chitosan yarns (CSy) loaded with tranexamic acid (TA) and Propolis (P). P/TA@CSy has good toughness with a breaking strength of 41.3 Pa, benefiting from the twisting structure and Propolis coating. A short coagulation time of 456 s was achieved for P/TA@CSy because of the potent blood absorption ability from the effective attachment of tranexamic acid. Moreover, excellent antibacterial ability was obtained with the antibacterial rates against E. coli of 94.73 %, S. aureus of 99.99 % and S. mutans of 99.99 %, contributing to Propolis's antibacterial ability. In addition, suppression of the expression of pro-inflammatory cytokines (IL-6 and TNF-α) was found, which could prevent wound infection. P/TA@CSy displayed excellent cytocompatibility with the cell activity of 100 % after 24 h. Therefore, P/TA@CSy could rapidly respond to gingival hemostasis and infection prevention, showing excellent potential in dental treatment., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives : Polydeoxyribonucleotides (PDRN), composed of DNA fragments derived from salmon DNA, is widely recognized for its regenerative properties. It has been extensively used in medical applications, such as dermatology and wound healing, due to its ability to enhance cellular metabolic activity, stimulate angiogenesis, and promote tissue regeneration. In the field of dentistry, PDRN has shown potential in promoting periodontal healing and bone regeneration. This study aims to investigate the effects of PDRN on the morphology, survival, and osteogenic differentiation of gingiva-derived stem cell spheroids, with a focus on its potential applications in tissue engineering and regenerative dentistry. Materials and Methods : Gingiva-derived mesenchymal stem cells were cultured and formed into spheroids using microwells. The cells were treated with varying concentrations of PDRN (0, 25, 50, 75, and 100 μg/mL) and cultivated in osteogenic media. Cell morphology was observed over seven days using an inverted microscope, and viability was assessed with Live/Dead Kit assays and Cell Counting Kit-8. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity and calcium deposition. The expression levels of osteogenic markers RUNX2 and COL1A1 were quantified using real-time polymerase chain reaction. RNA sequencing was performed to assess the gene expression profiles related to osteogenesis. Results : The results demonstrated that PDRN treatment had no significant effect on spheroid diameter or cellular viability during the observation period. However, a PDRN concentration of 75 μg/mL significantly enhanced calcium deposition by Day 14, suggesting increased mineralization. RUNX2 and COL1A1 mRNA expression levels varied with PDRN concentration, with the highest RUNX2 expression observed at 25 μg/mL and the highest COL1A1 expression at 75 μg/mL. RNA sequencing further confirmed the upregulation of genes involved in osteogenic differentiation, with enhanced expression of RUNX2 and COL1A1 in PDRN-treated gingiva-derived stem cell spheroids. Conclusions : In summary, PDRN did not significantly affect the viability or morphology of gingiva-derived stem cell spheroids but influenced their osteogenic differentiation and mineralization in a concentration-dependent manner. These findings suggest that PDRN may play a role in promoting osteogenic processes in tissue engineering and regenerative dentistry applications, with specific effects observed at different concentrations.

Chlorhexidine (CHX) is a prime choice to control the oral microbiota. However, it's a chemical agent leading to side effects such as teeth strains, taste disturbance, and desquamation of oral mucosa. Alternatively, the lactoferrin and oxygen-based Blue®M has been introduced as an alternative to the CHX, not disturbing tissue repair. Therefore, the study aimed to evaluate the effects of Blue®M and CHX on oral human fibroblasts (HGF-1) and keratinocytes (NOK-SI). Cell cultures using HGF-1 and NOK-SI evaluated cell proliferation, cell cycle, apoptosis and necrosis, and migration. In the dose-effect test, Blue®M reduced the HGF-1 sample in a 4-fold concentration than CHX (CHX: 173.07 ±10.27; Blue®M: 43.86 ±3.04). The proliferation test revealed an eightfold reduction of the sample for CHX, while for Blue®M, the proliferation rate was eighteen times lower. The apoptosis and necrosis rates increased by 25% (p<0.0001) for HGF-1 for both substances. In NOK-SI, the apoptosis rates increased by 10% (p=0.02) and 15% (p=0.001) for CHX and Blue®M, respectively. Furthermore, the fibroblast had a lower capacity for wound closure in the Scratch Assay (monolayer cell migration) for Blue®M. Despite the limitations of this in vitro study, the results of the lactoferrin and oxygen-based Blue®M demonstrated cytotoxicity in doses over the Minimum inhibitory concentration and Minimum bactericidal concentration for Oral fibroblasts (HGF- 1) and Keratinocytes (NOK-SI)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Aims: This study aimed to investigate the effects of Umbelliferone (UMB) on the inflammation underlying alveolar bone resorption in mouse periodontitis., Methods: Male Swiss mice subjected to a ligature of molars were grouped as non-treated (NT), received UMB (15, 45, or 135 mg/kg) or saline daily for 7 days, respectively, and were compared with naïve mice as control. Gingival tissues were evaluated by myeloperoxidase (MPO) activity and interleukin-1β level by ELISA. The bone resorption was directly assessed on the region between the cement-enamel junction and the alveolar bone crest. Microscopically, histomorphometry of the furcation region, immunofluorescence for nuclear factor-kappa B (NF-ĸB), and immunohistochemistry for tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were performed. Systemically, body mass variation and leukogram were analyzed., Results: Periodontitis significantly increased MPO activity, interleukin-1β level, and NF-ĸB+ immunofluorescence, and induced severe alveolar bone and furcation resorptions, besides increased TRAP+ and CTSK+ cells compared with naïve. UMB significantly prevented the inflammation by reducing MPO activity, interleukin-1β level, and NF-ĸB+ intensity, besides reduction of resorption of alveolar bone and furcation area, and TRAP+ and CTSK+ cells compared with the NT group. Periodontitis or UMB treatment did not affect the animals systemically., Conclusion: UMB improved periodontitis by reducing inflammation and bone markers., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: For treatment of medication-related osteonecrosis of the jaw, one proposed approach is the use of a topical agent to block entry of these medications in oral soft tissues. We tested the ability of phosphonoformic acid (PFA), an inhibitor of bisphosphonate entry through certain sodium-dependent phosphate contransporters (SLC20A1, 20A2, 34A1-3) as well as Dynasore, a macropinocytosis inhibitor, for their abilities to prevent zoledronate-induced (ZOL) death in human gingival fibroblasts (HGFs)., Methodology: MTT assay dose-response curves were performed to determine non-cytotoxic levels of both PFA and Dynasore. In the presence of 50 μM ZOL, optimized PFA and Dynasore doses were tested for their ability to restore HGF viability. To determine SLC expression in HGFs, total HGF RNA was subjected to quantitative real-time RT-PCR. Confocal fluorescence microscopy was employed to see if Dynasore inhibited macropinocytotic HGF entry of AF647-ZOL. Endosomal acidification in the presence of Dynasore was measured by live cell imaging utilizing LysoSensor Green DND-189. As a further test of Dynasore's ability to interfere with ZOL-containing endosomal maturation, perinuclear localization of mature endosomes containing AF647-ZOL or TRITC-dextran as a control were assessed via confocal fluorescence microscopy with CellProfiler™ software analysis of the resulting photomicrographs., Results: 0.5 mM PFA did not rescue HGFs from ZOL-induced viability loss at 72 hours while 10 and 30 μM geranylgeraniol did partially rescue. HGFs did not express the SLC transporters as compared to the expression in positive control tissues. 10 μM Dynasore completely prevented ZOL-induced viability loss. In the presence of Dynasore, AF647-ZOL and FITC-dextran co-localized in endosomes. Endosomal acidification was inhibited by Dynasore and perinuclear localization of both TRITC-dextran- and AF647-ZOL-containing endosomes was inhibited by 30 μM Dynasore., Conclusion: Dynasore prevents ZOL-induced viability loss in HGFs by partially interfering with macropinocytosis and by inhibiting the endosomal maturation pathway thought to be needed for ZOL delivery to the cytoplasm.

Objective: To develop a novel calcium silver zeolite (Ca-Ag-Zeo) and assess its biocompatibility, physiochemical properties and antimicrobial effects., Methods: Ca-Ag-Zeo was synthesized using ion-exchange method with calcium chloride, silver nitrate and Zeolite X (Zeo). Silver zeolite X (Ag-Zeo) and Zeo were set as control. The chemical structure, morphology, crystal structure and elemental composition of Ca-Ag-Zeo was characterized by X-ray diffraction spectrum, scanning electron microscopy, transmission electron microscopy and energy dispersive spectroscopy, respectively. Its biocompatibility on the human gingival fibroblasts was assessed by cell counting kit-8 assay. Its physiochemical properties were determined by the released calcium and silver ion using Inductive Coupled Plasma Emission Spectrometry for up to 12 weeks. The antimicrobial properties on Streptococcus mutans, Lactobacillus acidophilus, Lactobacillus casei, and Candida albicans were assessed by minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) assay., Results: Ca-Ag-Zeo with a hexagonal cage structure was synthesized. As for biocompatibility, the half-maximal inhibitory concentration (± SD in mg/mL) of Ca-Ag-Zeo, Ag-Zeo and Zeo in human gingival fibroblasts were 0.52 ± 0.05, 0.15 ± 0.01 and 3.35 ± 0.58, respectively (Zeo > Ca-Ag-Zeo > Ag-Zeo; p < 0.05). As for physiochemical properties, the accumulated ion release (± SD in mg) of Ca-Ag-Zeo, Ag-Zeo and Zeo were 0.011 ± 0.003, 0 and 0 for calcium ion, respectively (Ca-Ag-Zeo > Ag-Zeo, Zeo; p < 0.001), and 0.213 ± 0.032, 0.209 ± 0.019 and 0 for silver ion, respectively (Ca-Ag-Zeo, Ag-Zeo > Zeo; p < 0.001). As for anti-microbial ability, the MBC/MFC (mg/mL) of Ca-Ag-Zeo, Ag-Zeo and Zeo were 32, 16 and > 256 against Streptococcus mutans; 32, 16, > 256 against Lactobacillus acidophilus; 16, 16, and 256 against Lactobacillus casei; 0.25, 0.125; and 2, 1, > 256 against Candida albicans, respectively., Conclusion: A novel Ca-Ag-Zeo was developed. It presented better biocompatibility compared to Ag-Zeo. It released calcium and silver ions sustainably, and it could inhibit the growth of common cariogenic microorganisms., (© 2024. The Author(s).)

This study investigated the efficacy and safety of a propolis-mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multicentered, randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on the changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. The results revealed that the PMEC group showed a significantly reduced expression of all measured GCF biomarkers compared to the placebo group ( p < 0.0001) at 8 weeks, including substantial reductions in IL-1β, PGE2, MMP-8, and MMP-9 levels compared to the baseline. While clinical parameters trended towards improvement in both groups, the intergroup differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

Sodium fluoride-polyvinyl alcohol (NaF-PVA) tape was developed to deliver fluoride to teeth by adding fluoride to polymer tape. Previous studies have demonstrated that tapes are effective and have antimicrobial properties. This study aimed to evaluate the cytotoxicity of two fluoride-releasing adhesive tapes. We investigated two polyvinyl alcohol (PVA) tapes: (i) a fluoride-PVA (F-PVA) tape, and (ii) a pullulan-incorporated F-PVA (PF-PVA) tape. The cytotoxicity test was conducted on human gingival fibroblasts (HGF) and human periodontal ligament (PDL) cells. Using an adhesive tape containing fluoride, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on these cells. Genetic analysis of the cells was performed to conduct a stability test on humans. In the MTT assay, PF-PVA had 66% greater cytotoxicity than control by PDL and 69% by HGF. F-PVA showed less cytotoxicity than PF-PVA by 29% in PDL and 33% in HGF. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed as gene expression analyses. GO analysis indicated that PF-PVA displayed more expression changes of genes related to cytotoxicity than F-PVA. In addition, GSEA found more inflammatory response associations in PF-PVA than in F-PVA. MTT and genetic testing yielded comparable results., Competing Interests: The authors declare no conflict of interest., (©2024 The Author(s). Published by MRE Press.)

Background: Gingivitis is a dysbiotic condition characterized by persistent inflammation caused by a disease-associated multispecies bacterial population that has established itself in the subgingival region., Aim: The objectives of this study are to analyze the anti-inflammatory activity of sappan wood extract cream (SWC) in Porphyromonas gingivalis induced-periodontitis rats model., Methods: In this study, rats were infected with the gingiva with P. gingivalis as an inducer for gingivitis rats model for 14 days. The SWC were treated topically into the infected tissue. The inflammation and angiogenesis of gingival tissue was analyzed using histological examination. An immunohistochemistry (IHC) assay was used to analyze the nuclear factor kappa-B (NF-kB) protein expression. Masson Trichrome (MT) assay was used to analyze the histopathology of collagen Scores. The tumor necrosis factor-α (TNF-α), Interleukin-1 β (IL-1β), IL-6, and P38 genes expression were measured using quantitative real time-polymerase chain reaction., Results: The induction of P. gingivalis -induced gingivitis in rats model was indicated by reddish gingiva and bacterial plaque. MT tests showed that SWC increased collagen density, and Haematoxylin and Eosin (H&E) test showed increased angiogenesis and in contrast, lowered inflammation score. IHC test showed that SWC decreased the expression of NF-kB protein. The TNF-α, IL-1β, IL-6, and P38 gene expression were also decreased due to the SWC treatment., Conclusion: SWC proves that it has anti-inflammatory activity which has the potential to prevent or treat gingivitis., Competing Interests: The authors declare that there is no conflict of interest.

Background and Objectives: Gingival retraction is a critical pre-impression procedure in fixed prosthodontics, crucial for exposing tooth margins and ensuring accurate impressions for restorations like crowns and bridges. This study aimed to evaluate the absorptive capacity of different gingival retraction cords. Materials and Methods: Ninety samples each of Ultrapak (Ultradent, South Jordan, UT, USA) #00, braided cord, coreless thread, and monofilament thread (totaling 270 samples) were immersed in 0.9% NaCl, 10% aluminum chloride, and 12.7% ferrous sulfate solutions for 120, 300, and 1200 s. The liquid absorption capacity was measured using a gravimetric method, and the data were analyzed using an F-test, setting the significance threshold at p < 0.05. Results: The results revealed statistically significant differences in absorption, particularly for aluminum chloride and ferric sulfate ( p < 0.001). Ultrapak demonstrated the highest absorption, followed by the coreless cotton thread, while the monofilament thread absorbed the least, especially at 1200 s. Conclusions: These findings indicate that Ultrapak's superior absorption could enhance moisture control during procedures, highlighting the importance of selecting an appropriate retraction cord for optimal clinical outcomes. Further research is needed to confirm these findings in a clinical setting.

There is a strong association between vitamin D levels and periodontal disease based on numerous epidemiological studies. We have previously shown that experimental deficiency of serum vitamin D in mice leads to gingival inflammation and alveolar bone loss. Treatment of cultured oral epithelial cells with the active form of vitamin D, 1,25(OH) 2 vitamin D 3 (1,25(OH) 2 D 3 ), inhibits the extracellular growth and intracellular invasion of bacteria associated with periodontal disease. Maintenance of periodontal health may be due in part to the anti-inflammatory activities of vitamin D. Furthermore, this hormone can induce the expression of an antimicrobial peptide in cultured oral epithelial cells. We have shown that oral epithelial cells are capable of converting inactive vitamin D to the active form, suggesting that topical treatment of the oral epithelium with inactive vitamin D could prevent the development of periodontitis. We subjected mice to ligature-induced periodontitis (LIP), followed by daily treatment with inactive vitamin D or 1,25(OH) 2 D 3 . Treatment with both forms led to a reduction in ligature-induced bone loss and inflammation. Gingival tissues obtained from vitamin D-treated LIP showed production of specialized proresolving mediators (SPM) of inflammation. To examine the mechanism, we demonstrated that apical treatment of 3-dimensional cultures of primary gingival epithelial cells with vitamin D prevented lipopolysaccharide-induced secretion of proinflammatory cytokines and led to a similar production of SPM. Analysis of the oral microbiome of the mice treated with vitamin D showed significant changes in resident bacteria, which reflects a shift toward health-associated species. Together, our results show that topical treatment of oral tissues with inactive vitamin D can lead to the maintenance of periodontal health through the regulation of a healthy microbiome and the stimulation of resolution of inflammation. This strongly supports the development of a safe and effective vitamin D-based topical treatment or preventive agent for periodontal inflammation and disease., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Periodontitis causes an increase in several bioactive agents such as interleukins (IL), tumor necrosis factor (TNF)-α and receptor activator of NF-kB ligand (RANKL), which induce the osteoclast formation and activity. Since diacerein exerts anti-TNF-α and anti-IL-1 effects, alleviating bone destruction in osteoarthritis, we investigated whether this drug inhibits the formation and survival of osteoclast in the periodontitis. Rats were distributed into 3 groups: 1) group with periodontitis treated with 100 mg/kg diacerein (PDG), 2) group with periodontitis treated with saline (PSG) and group control (CG) without any treatment. After 7, 15 and 30 days, the maxillae were collected for light and transmission electron microscopy analyses. Gingiva samples were collected to evaluate the mRNA levels for Tnf, Il1b, Tnfsf11 and Tnfrsf11b by RT-qPCR. In PDG, the expression of Tnf and Il1b genes reduced significantly compared to PSG, except for Tnf expression at 7 days. The number of osteoclasts reduced significantly in the PDG in comparison with PSG at 7 and 15 days. In all periods, the IL-6 immunoexpression, RANKL/OPG immunoexpression and mRNA levels of Tnfsf11/Tnfrsf11b ratio were significantly lower in PDG than in PSG. PDG exhibited significantly higher frequency of TUNEL-positive osteoclasts than in PSG and CG at all time points. Osteoclasts with caspase-3-immunolabelled cytoplasm and nuclei with masses of condensed chromatin were observed in PDG, confirming osteoclast apoptosis. Diacerein inhibits osteoclastogenesis by decreasing Tnf and Il1b mRNA levels, resulting in decreased RANKL/OPG ratio, and induces apoptosis in osteoclasts of alveolar process of rat molars with periodontitis., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest concerning the manuscript entitled “ Reduction of osteoclast formation and survival following supression of cytokines by diacerein in periodontitis” submitted for publication in Biomedicine & Pharmacotherapy. We also confirm that this manuscript is original and has not been submitted for publication elsewhere., (Copyright © 2024. Published by Elsevier Masson SAS.)

Aim: Resveratrol is a natural polyphenolic compound with biological activities such as anti-inflammation and antioxidation. Its anti-fibrotic effect has been experimentally demonstrated in the pancreas and liver. This study aims to determine the anti-proliferative effect of resveratrol on fibroblasts obtained from hyperplastic gingival tissues from a patient diagnosed with Juvenile Hyaline Fibromatosis (JHF)., Materials and Methods: Primary gingival fibroblast cell lines were obtained from gingival growth tissues by the gingivectomy of a patient with JHF. Gingival fibroblasts were treated with or without 3 different doses of resveratrol (50, 100, 200 µM). Cytotoxicity and cell proliferation were evaluated after 24, 48, and 72 h. Collagen, TGF, and CTGF were analyzed by ELISA in the 48-hour supernatants., Results: All three doses of resveratrol suppressed the proliferation of JHF gingival fibroblasts at 24 and 48 h without showing any cytotoxic effect compared to the control group (p < 0.0001). At 72 h, 100 and 200 µM resveratrol showed significantly less proliferation (p < 0.0001), less collagen, CTGF, and TGF- β (p < 0.001) than the control group., Conclusion: Resveratrol had a profound anti-proliferative effect on gingival fibroblasts obtained from gingival enlargements with JHF, suggesting that it can be used as a therapeutic to prevent excessive cell growth by suppressing collagen, CTGF, and TGF- β synthesis in the pathogenesis of hyperplasia., (© 2024. The Author(s).)

Following implant placement, a soft tissue barrier will form at the healing abutment connection called peri-implant mucosa. The dimension of this anatomical structure seems to play a key role in maintaining long-term peri-implant and marginal bone level stability. In its early stages, soft tissue healing is a process involving many cellular and molecular events. Enamel matrix derivative (EMD) may improve and accelerate soft tissue wound healing and inflammatory resolution. In the present split-mouth randomized clinical trial, EMD was used to influence the early phase of soft tissue healing around dental implants placed with a single-stage approach into a completely healed ridge. A total of 60 implants were placed in 30 patients (2 implants per patient, one in the test group and one in the control group). In the test sites, EMD was administered around the healing abutment before soft tissues were sutured. Soft tissue healing index (HI) and secondary endpoints (clinical, radiographic, and patientreported outcomes) were measured. Better outcomes were recorded in patients receiving EMD for all parameters. The present results support the use of EMD to improve and accelerate soft tissue wound healing around implants.

The purpose of this research was to investigate the effect of toluidine blue (TB) mediated photodynamic therapy (PDT) on the inhibition of lipopolysaccharide (LPS)-induced inflammation in rat gingival fibroblasts through in vitro experiments. Rat gingival fibroblasts were divided into five groups: (1) control, (2) LPS treatment, (3) laser treatment, (4) TB treatment (1.0 µg/mL), and (5) PDT treatment (TB plus laser irradiation at 320 mW/cm 2 for 240 s). After 24 h, cell growth activity was measured using MTT assay. The levels of receptor activator for nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in the cell culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA). Nuclear proteins were extracted and the phosphorylation levels of phosphorylated nuclear factor-κB/p65 (p-p65) and phosphorylated inhibitor of nuclear factor-κB (p-IκBα) were determined using Western Blot. MTT results showed no significant difference in cell viability between the groups (P > 0.05). After LPS induction, OPG expression decreased, RANKL expression increased, and the OPG/RANKL ratio decreased, which was different from the control group (P < 0.05). After PDT treatment, OPG expression increased, RANKL expression decreased (P < 0.05), and the OPG/RANKL ratio increased (P < 0.05). Compared to the control group, there was no significant difference in OPG and RANKL expression or the OPG/RANKL ratio (P > 0.05). The activation of NF-κB was closely related to the phosphorylation levels of p-p65 and p-IκBα. LPS significantly up-regulated p-p65 and p-IκBα expression (P < 0.05), while PDT treatment decreased their phosphorylation levels (P < 0.05). TB-PDT treatment can inhibit NF-κB signaling pathway activation, decrease RANKL and OPG expression, and reduce the OPG/RANKL ratio, thereby reducing inflammation and playing a role in periodontitis treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

To evaluate the effect of high-graduation chronic ethanol (EtOH) intake on bone and periodontal tissues of rats. Male Wistar rats (250 g) were divided into two groups of n = 12 each one. EtOH (5 ml of 3 g/kg) was administered to the experimental group by gastric gavage twice a day for 20 days and the control group received water under the same conditions. The rats were euthanized and used to perform biochemical determination in plasma and gingival tissue, and histological and biomechanical studies in the femur and mandibular tissues. Alcohol increased both TNFα (p < 0.01) and PGE2 (p < 0.05) in plasma and gingiva (p < 0.05) as compared to controls. In addition, EtOH increased the alveolar bone loss as evidenced by the increased distance between the cement enamel junction and the alveolar crest (p < 0.01), the lower % of interradicular bone expressed as bone area/total area (B.Ar/T.Ar, p < 0.05) and the larger periodontal space (p < 0.05), as compared to controls. Likewise, the mandibular microtomographic analysis in alcoholized rats revealed a lower % of interradicular bone volume/total volume (BV/TV, p < 0.05), greater trabecular separation (p < 0.05) and greater % trabecular porosity (p < 0.05) than controls. No biomechanical alteration was observed in lower jaws, while the femur of alcoholized rats presented a decrease in the structural bone properties (p < 0.001), as a systemic consequence of deterioration of the diaphyseal architecture (p < 0.01) without changes in material properties. The consumption of high doses of alcohol produces deleterious effects on periodontal tissues that could be due not only to local but also systemic effects., (© 2023. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Background: Boric acid (BA) has been found to have therapeutic effects on periodontal disease through beneficially affecting antibacterial, anti-viral, and anti-inflammatory actions., Methods: This study was conducted to determine the effect of BA on cell viability and on mRNA expressions of proinflammatory and anti-inflammatory cytokines and on oxidative stress enzymes induced by IL-1β (1 ng/mL) in Human Gingival Fibroblasts (HGF) cultured for 24 and 72 h in DMEM media. The BA concentrations added to the media were 0.09 %, 0.18 %, 0.37 %, and 0.75 %., Results: All of the BA concentrations increased the viability of cell cultured in DMEM media only, indicating that these concentrations were not toxic and actually beneficial to cell viability. The addition of 1 ng/m: of IL-1β decreased cell viability that was overcome by all concentrations of BA at both 24 and 72 h. The IL-1β addition to the media increased the expressions of the proinflammatory cytokines IL-1β, IL-6, IL-8, and IL-17; the anti-inflammatory cytokine IL-10; and the oxidative stress enzymes superoxide dismutase (SOD0 and glutathione peroxidase (GPX). The IL-1β induced increase mRNA expression of IL-1β was decreased at 24 h by the 0.37 % and 0.75 % BA additions to the media and decreased in a dose-dependent manner by all concentrations of BA at 72 h. The IL-1β induced increase in the expression of IL-6 was decreased in dose-dependent manner at 72 h by BA. All BA concentrations decreased the IL-1β induced expression of IL-8 at both 24 and 72 h. The induced increase in IL-17 by IL-1β was not significantly affected by the BA additions. The increase in the anti-inflammatory cytokine IL10 induced by IL-1β was increased further by all BA additions in dose dependent manner at both 24 and 72 h. The mRNA expressions of SOD and GPX increased by IL-1β were further increased by the 0.37 % and 0.75 % BA concentrations at 72 h., Conclusions: These findings indicate that BA can significantly modulate the cytokines that are involved in inflammatory stress and reactive oxygen species action and thus could be an effective therapeutic agent in the treatment of periodontal disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The aim of the present study was to investigate the anti‑inflammatory effect of Oroxylin A in periodontitis and its potential role through heme oxygenase‑1 (HO‑1). Primary rat gingival fibroblasts (RGFs) were cultured using the tissue block method and identified by immunofluorescence. Following lipopolysaccharide (LPS) stimulation of RGFs, Oroxylin A was administered at 50, 100, 200 or 400 µg/ml. Reverse transcription‑quantitative PCR was used to assess mRNA expression of cyclooxygenase (COX)‑2, TNF‑α, RANKL and osteoprotegerin (OPG). Western blotting was used to detect protein expression levels of COX ‑2, TNF‑α, RANKL and OPG. Following HO‑1 knockdown, the same treatment was performed. The expression of COX‑2 in rat gingival tissue was observed by immunohistochemistry. One‑way analysis of variance and Student's t test were used for statistical analysis. Oroxylin A downregulated mRNA expression of COX‑2, TNF‑α, RANKL and OPG in LPS‑induced RGFs. With increase of Oroxylin A dose, the expression of HO‑1 was gradually upregulated. When HO‑1 was knocked down, Oroxylin A did not downregulate the expression of COX‑2, TNF‑α, RANKL and OPG in LPS‑induced RGFs. Immunohistochemical results showed that expression of COX‑2 was downregulated by Oroxylin A, and the expression of TNF‑α, RANKL and OPG were also downregulated. Oroxylin A decreased expression of inflammatory cytokines in LPS‑induced RGFs and had a good inhibitory effect on periodontitis in rats.

Nanocoatings based on plant polyphenols have been recently suggested as a potent strategy for modification of implant surfaces for enhancing host cell attachment and reducing bacterial colonisation. In this study we aimed to investigate how serum proteins impact the early adhesion dynamics of human gingival fibroblasts onto titanium surfaces coated with tannic acid (TA). Silicate-TA nanocoatings were formed on titanium and pre-conditioned in medium supplemented with 0, 0.1, 1 or 10% FBS for 1 hour. Dynamics of fibroblasts adhesion was studied using quartz crystal microbalance with dissipation (QCM-D). Time-lapse imaging was employed to assess cell area and motility, while immunofluorescence microscopy was used to examine cell morphology and focal adhesion formation. Our results showed that in serum-free medium, fibroblasts demonstrated enhanced and faster adhesion to TA coatings compared to uncoated titanium. Increasing the serum concentration reduced cell adhesion to nanocoatings, resulting in nearly complete inhibition at 10% FBS. This inhibition was not observed for uncoated titanium at 10% FBS, although cell adhesion was delayed and progressed slower compared to serum-free conditions. In addition, 1% FBS dramatically reduced cell adhesion on uncoated titanium. We revealed a positive relationship between changes in dissipation and changes in cell spreading area, and a negative relationship between dissipation and cell motility. In conclusion, our study demonstrated that serum decreases fibroblasts interaction with surfaces coated with TA in a concentration dependent manner. This suggests that controlling serum concentration can be used to regulate or potentially prevent fibroblasts adhesion onto TA-coated titanium surfaces.