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Objective: This study evaluated the influence of melatonin supplementation on tissue's response of endodontic sealers in Wistar rats., Methodology: Forty-eight rats received subcutaneous implants of four polyethylene tubes: one empty (control) and three filled with endodontic sealers (AH Plus, Endofill and Sealapex). Half of the animals were supplemented with melatonin (ME) and the remaining treated with water (WA) for 15 days before the implantation until euthanasia, forming the groups: control-WA, AH Plus-WA, Endofill-WA, Sealapex-WA, Control-ME, AH Plus-ME, Endofill-ME and Sealapex-ME. After 5, 15 and 30 days, (n = 8) tubes were removed and evaluated in H&E., immunohistochemistry, PSR, VK and POL. The results were statistically analyzed (p < 0.05)., Results: In animals treated with water, Endofill-WA evoked more intense inflammatory infiltrate compared to AH Plus-WA and Control-WA in a 30-day period (p < 0.05). In animals supplemented with melatonin, there was any difference among endodontic sealers' response in any period of analysis (p > 0.05). Comparing the individual response of each sealer, over a 30-day period, Endofill-ME and Sealapex-ME showed less inflammatory infiltrate compared to Endofill-WA and Sealapex-WA, respectively (p < 0.05). Immunostaining for IL-6 and TNF-α was less intense for all groups in animals supplemented with melatonin, in most periods, except for the Endofill sealer (p < 0.05). Furthermore, Endofill-ME at 5 days and AH-Plus-ME at 30 days showed a higher percentage of mature collagen fibers compared to the Endofill-WA and AH Plus-WA, respectively (p < 0.05). Positive structures for von Kossa staining and birefringent to polarized light were observed only for Sealapex-WA and Sealapex-ME in all periods., Conclusions: It can be concluded that melatonin influences the tissue response to endodontic sealers, modulating the inflammatory and reparative process., Competing Interests: Declarations. Conflict of interest: The authors have no conflict of interest to declare that is relevant to the content of this article., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Bone regeneration remains a critical challenge in regenerative medicine, particularly in dentistry, where conditions such as periodontal disease and trauma can lead to significant bone defects. Traditional treatment methods, such as autogenous bone grafting, face limitations, including donor site morbidity and postoperative complications. Recent advancements in biomaterials, particularly silk fibroin-based scaffolds, have shown promise due to their excellent biocompatibility and tunable mechanical properties. Incorporating bioactive glass and metal ions, such as cobalt, into these scaffolds can enhance osteogenic properties and antibacterial effects, creating an optimal environment for bone regeneration. The primary objective of this study was to develop and characterize SilkMA/silicated-chlorinated cobalt-doped bioactive glass composites with the potential for bone regeneration applications. Utilizing the sol-gel method, we synthesized cobalt-doped bioglass, enhancing its bioactivity and antibacterial properties. Mechanical testing, swelling assessments, degradation analysis, and in vitro evaluations using alveolar bone-derived mesenchymal stem cells (aBMSCs) demonstrated the scaffolds' cytocompatibility and favorable physical properties. The structural integrity of the electrospun fibers was confirmed through Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Raman Spectroscopy analyses. Incorporating bioglass reduced swelling ratios, while in vitro assays showed that cobalt ions effectively inhibited the biofilm formation of Porphyromonas gingivalis. In vivo analysis using hematoxylin-eosin and von Kossa (vK) staining demonstrated that the SilkMA + 20% BGCo scaffold elicited a minimal inflammatory response, confirming its biocompatibility. However, the absence of positively stained structures in the vK analysis indicated its lack of mineralization potential. In sum, SilkMA/BGCo scaffolds showed promising in vitro potential for bone tissue regeneration and excellent biocompatibility in vivo despite lacking calcium deposition. Further studies with alternative in vivo models are needed to confirm their efficacy., 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.)

The aim of this study was to investigate the influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis (AP) in Wistar rats. Fifty-six rats were submitted to pulp exposure of the lower left first molar for the induction of AP. On the same day, intraperitoneal antibiotic therapy was administered once a day, for 15 days, until euthanasia. The groups were formed according to the different treatments (n = 8): C-control; GEN-treated with gentamicin (10 mg/Kg); AC-treated with amoxicillin (100 mg/Kg); MZ-treated with metronidazole (40 mg/Kg); AMP-treated with ampicillin (100 mg/Kg); AMC group-treated with amoxicillin + clavulanic acid (100 mg/kg); CLI-treated with clindamycin (60 mg/kg). After euthanasia, the jaws were collected and processed for (1) histological and histometric analysis using hematoxylin and eosin staining, (2) analysis of collagen fibers using Picrosirius Red staining and (3) bacteriological analysis using Brown-Brenn staining. The data were analyzed statistically (p < 0.05). AP induction was confirmed in all groups. The AMC group had the lower intensity of inflammatory infiltrate (p = 0.028) and less periapical bone resorption compared to control (p = 0.006). Regarding collagen maturation, PSR staining revealed a predominance of mature collagen fibers in all groups. The AC and AMC groups had the lower amount of mature fibers and the highest amount of immature fibers, compared to all other groups (p < 0.001). All groups showed bacterial contamination; however, the AC and AMC groups showed a lower extent of bacterial contamination compared to the control (p < 0.001). It can be concluded that systemic antibiotic therapy influences the development and progression of induced AP., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

The evolution of biomaterials engineering allowed for the development of products that improve outcomes in the medical-dental field. Bioglasses have demonstrated the ability to either compose or replace different materials in dentistry. This study evaluated the cytotoxicity, biocompatibility, calcium deposition, and collagen maturation of 45S5 bioglass experimental paste and Bio-C Temp, compared to calcium hydroxide (Ca(OH) 2 ) paste. The 45S5 bioglass and Ca(OH) 2 powder were mixed with distilled water (ratio 2:1); Bio-C Temp is ready-for-use. Dental pulp cells were exposed to the materials' extracts (1:2 and 1:4 dilutions; 24, 48, and 72 h) for MTT and live/dead analyses. Polyethylene tubes filled with the pastes, or left empty (control), were implanted on the dorsum of 16 rats. After 7 and 30 days (n = 8/period), the rats were euthanized and the specimens were processed for hematoxylin-eosin (H&E), von Kossa (vK), and picrosirius red (PSR) staining, or without staining for polarized light (PL) birefringence analysis. A statistical analysis was applied ( p < 0.05). There was no difference in cell viability among Ca(OH) 2 , 45S5 bioglass, and the control, across all periods and dilutions ( p > 0.05), while Bio-C Temp was cytotoxic in all periods and dilutions compared to the control ( p < 0.05). Regarding biocompatibility, there was a reduction in inflammation from 7 to 30 days for all groups, without significant differences among the groups for any period ( p > 0.05). The fibrous capsules were thick for all groups at 7 days and thin at 30 days. All materials showed positive structures for vK and PL analysis. At 7 days, the control and 45S5 bioglass showed more immature collagen than the other groups ( p < 0.05); at 30 days, 45S5 bioglass had more immature than mature collagen, different from the other groups ( p < 0.05). In conclusion, Bio-C Temp presented cytotoxicity compared to the other materials, but the three pastes showed biocompatibility and induced calcium deposition. Additionally, the bioglass paste allowed for marked and continuous collagen proliferation. This study contributed to the development of new biomaterials and highlighted different methodologies for understanding the characteristics of medical-dental materials.

The aim of this study was to evaluate the influence of liver fibrosis (LF) on the expression of Toll-like receptors (TLR) 2 and 4 in apical periodontitis (AP) in Wistar rats. Forty Wistar rats were allocated in the following groups (n = 10): C-control; AP-apical periodontitis; LF-liver fibrosis; AP + LF-rats with AP and LF. LF and AP were induced by established methodologies. Histological, bacteriological, and immunohistochemical analyses were performed according to pre-established scores. For comparisons between AP and AP + LF groups, the Mann-Whitney test was used (P < .05). The livers of the LF and AP + LF groups showed generalized portal inflammatory infiltrate and collagen fibers confirming the presence of LF. Histopathological analysis in the maxilla of the AP + LF group showed areas of necrosis comprising the entire dental pulp and periapical tissue surrounded by a more intense inflammatory infiltrate than observed in the AP group (P = 0.032). A significant number of specimens in the AP + LF group showed microorganisms beyond the apical foramen adhered to the extraradicular biofilm, demonstrating greater invasion compared to the AP group (P = .008). Immunohistochemical analysis showed a large number of cells immunoreactive for TLR2 and TLR4 in the AP + LF group, compared to the AP group (P < 0.05). Liver fibrosis favors the inflammation and contamination of microorganisms in apical periodontitis and triggers the expression of TLR2 and TLR4, modulating innate immunity response in periapical lesions., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Laser ablation therapy (LA) uses Indocyanine Green dye (ICG) which efficiently absorbs laser energy and the increased temperature results in an instantaneous flame that chars tissue and microbes. Photodynamic therapy (PDT) uses different dyes that are activated by light to kill bacteria. This study evaluated the biocompatibility of the dye Curcumin (CUR), Methylene Blue (MB), and Indocyanine Green (ICG) before and after laser activation (ACT). Polyethylene tubes containing one of the dyes were implanted in the subcutaneous tissue of 32 rats (4 tubes per rat) which were divided into 8 groups: C - control (saline solution); C + ACT (Red Laser 660 nm); CUR; CUR + ACT (480 nm blue LED); MB; MB + ACT (Red Laser 660 nm); ICG; ICG + ACT (810 nm Infrared Laser). After 7 and 30 days (n = 8/time), the rats were euthanized and the tubes with the surrounding tissue were removed and processed for histological analysis of inflammation using H&E stain, and collagen fiber maturation using picrosirius red (PSR). A two-way analysis of variance statistical test was applied (p < 0.05). At 7 days, regardless of laser activation, the CUR group showed a greater inflammatory infiltrate compared to the ICG and control groups, and the MB group had a greater inflammation only in relation to the control (p < 0.05). At 30 days, CUR and MB groups showed a greater inflammatory infiltrate than the control (p < 0.05). ICG group was equal to the control in both periods, regardless of the laser activation (p > 0.05). Laser activation induced the proliferation of collagen immature fibers at 7 days, regardless of the dye (p < 0.05). The CUR group showed a lower percentage of immature and mature fibers at 7 days, compared to ICG and control (p < 0.05) and, at 30 days, compared to control (p < 0.05). Regardless of laser activation, the ICG showed the results of collagen maturation closest to the control (p > 0.05). It was concluded that all dyes are biocompatible and that laser activation did not interfere with biocompatibility. In addition, the maturity of collagen was adequate before and after the laser activation. These results demonstrate that the clinical use of dyes is safe even when activated with a laser., 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 B.V. All rights reserved.)

Aim: The aim of the study was to evaluate the effect of systemic curcumin administration on the severity of apical periodontitis (AP)., Methodology: Forty male Wistar rats weighing 250-280 g each, age 2.5 months, were distributed into four groups (n = 10): control untreated rats (C), control rats treated with curcumin (CUR), rats with pulp exposure-induced apical periodontitis (AP) and rats with pulp exposure-induced apical periodontitis treated with curcumin (AP-CUR). Curcumin treatment was administered orally once daily for 15 days before pulp exposure and continued for 30 days after pulp exposure. The rats were sacrificed at 30 days, and the jaws were collected and reconstructed in a programme specific for micro-CT. The jaws were processed for analysis of the inflammatory process using haematoxylin and eosin staining and immunohistochemical assays for interleukin tumour necrosis factor alpha (TNF-α), interleukin (Il)-6 and Il-1β. Tartrate-resistant acid phosphatase (TRAP) and osteocalcin (OCN) staining were used to analyse the resorptive process on the bone surface of periapical area. Kruskal-Wallis with Dunn's test was performed for nonparametric data and anova with Tukey's test for parametric data, p < .05., Results: Micro-CT revealed no statistically significant differences in bone resorption between the AP and AP-CUR groups (p > .05). The levels of inflammatory cell infiltration and immunoreactivity for the proinflammatory cytokines TNF-α, Il-6 and Il-1β were significantly higher in the periapical lesions of the AP group than in the AP-CUR group (p < .05). The number of TRAP-positive multinucleated cells was higher in the AP group than in the AP-CUR group (p < .05). In OCN-positive cells, no differences were observed between the AP and AP-CUR groups (p > .05)., Conclusions: Oral supplementation with curcumin had a significant effect on the AP severity in rats, suggesting an anti-inflammatory effect of curcumin on AP development., (© 2022 British Endodontic Society. Published by John Wiley & Sons Ltd.)

Aim: Natural substances such as omega-3 have been used in the medical field due to their numerous properties and, in particular, modulating effect on the systemic and local inflammatory processes. Thus, this study evaluated the influence of omega-3 supplementation on the subcutaneous tissue response of endodontic sealers in Wistar Rats., Methodology: Polyethylene tubes were implanted in the subcutaneous tissue of 48 animals (one empty for control and three filled with Sealapex, AH Plus or Endofill). The animals were treated with omega-3 (TO) or water (TW). Treatments started 15 days before implantation until euthanasia. After 5, 15 and 30 days (n = 8), animals were euthanized and polyethylene tubes and surrounding tissue were removed and processed for histological analysis. The inflammatory reaction was analysed by Haematoxylin and Eosin stain and immunolabelling for IL-6 and TNF-α. The collagen maturity was analysed by picrosirius red stain and calcium deposition by von Kossa stain and polarized light. Results were statistically analysed (p < .05)., Results: Amongst TW sealer groups, Endofill evoked a more intense inflammatory infiltrate compared with AH Plus and control in the 30-day period (p = .009). However, in TO sealer groups, there was no difference amongst the sealers and control in all periods (p > .05). Comparing each sealer as a function of the supplementation with water or omega-3, there are differences for Endofill (p = .001) and Sealapex (p = .005) in the 30-day period, presenting lower inflammatory infiltrate in the animals treated with omega-3. A higher percentage of immature fibres was observed at 15 and 30 days in the TO group, compared with the TW group (p < .05). The deposition of calcium particles was observed only by Sealapex in all periods, despite the supplementation procedure., Conclusions: Omega-3 supplementation influence the tissue reactions of endodontic sealers, modulating inflammation, the immunolabelling of IL-6 and TNF-α, the repair process and it does not interfere with calcium deposition., (© 2022 British Endodontic Society. Published by John Wiley & Sons Ltd.)

The systematic review tried to answer the following question: Does the melatonin administered systemically or topically ameliorate patients involved with oral health conditions or dental procedures? The systematic review has been registered in the PROSPERO (2021CRD42021095959). Eligibility criteria included only randomized controlled clinical trials (RCTs) with at least 10 participants that compared patients that received melatonin as a treatment before and/or after their oral intervention topically or systemically, with control patients. A search was performed in PubMed/MEDLINE, Web of Science, Cochrane Library, and Academic Google databases for articles up to February 2021. The Cochrane risk-of-bias tool for randomized clinical trials was used and revealed that the studies included presented low risk of bias for the majority of criteria assessed. It was selected 25 articles, of which only six did not demonstrate positive effects and three presented null effects with the use of melatonin. Melatonin has improved the inflammatory response in periodontal disease, dental surgeries, and mucositis of head and neck oncologic irradiated patients. In addition, it showed anxiolytic potential in patients that were submitted to dental procedures. In conclusion, melatonin favored the treatment of oral changes when used topically and systemically., (© 2021 Wiley Periodicals LLC.)

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been reported to exert important roles in the inflammatory response. There are many inflammatory diseases in dentistry which support the administration of ω-3 PUFAs as an adjunct therapy during the treatment of these diseases. The aim of this review was to evaluate the use of ω-3 PUFAs as an adjuvant therapy during the treatment of buccal diseases. The review showed that supplementation with ω-3 PUFAs was used for treatment of gingivitis, periodontal diseases, apical periodontitis, stomatitis, and orthodontic tooth movement. The results indicate that ω-3 PUFAs decreased the number of pro-inflammatory mediators in the gingival tissues of individuals with gingivitis and periodontitis. In apical periodontitis, the supplementation suppressed bone resorption and promoted bone formation in the periapical area of rats. During orthodontic movement, the supplementation showed a decrease of bone resorption in rats. It also showed that painful symptoms of recurrent aphthous stomatitis were alleviated in supplemented patients. In conclusion, the ω-3 PUFAs may be used as an adjuvant therapy in the treatment of inflammatory diseases that affect the oral cavity. However, more studies are required to elucidate the role of ω-3 PUFAs in decreasing oral cavity inflammatory processes., (© 2020 Wiley Periodicals LLC.)

Aim: To investigate the effects of liver fibrosis (LF) on the pro-inflammatory mediators and periapical bone resorption of apical periodontitis (AP) in rats., Methodology: Forty male Wistar rats were distributed into four groups: C - control, AP - rats with AP, LF - rats with LF, AP + LF - rats with AP and LF. LF was induced by carbon tetrachloride administration for 8 weeks and surgical bile duct ligation for 4 weeks; AP was induced in the teeth of rats by dental pulp exposure to the oral environment for 30 days. Jaws and livers were removed after euthanasia. Haematoxylin and Eosin (H&E) and Picrosirius Red (PSR) staining were used to confirm fibrosis in the livers. The jaws were analysed using H&E staining, immunohistochemical assays of interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α). Student's t-test and Mann-Whitney's U-test were used for statistical analysis (P < 0.05)., Results: Inflammatory infiltrate was moderate in the AP group and severe in the AP + LF group (P < 0.05). Periapical bone resorption was significantly larger in the AP + LF group compared with the AP group (P < 0.05). IL-1β, IL-6 and TNF-α levels were significantly higher in AP + LF group when compared to the AP group (P < 0.05)., Conclusion: More intense inflammatory infiltrate, greater amounts of pro-inflammatory cytokines and increased periapical bone resorption were observed in the presence of liver fibrosis in rats with exposed pulps., (© 2021 International Endodontic Journal. Published by John Wiley & Sons Ltd.)