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Aim: This systematic review was aimed at addressing the focused question: What is the protective potential of biological agents against alveolar bone resorption during the progression of experimental periodontitis (EP)? Material and Methods: The study protocol was registered in the Open Science Framework database (doi:10.17605/OSF.IO/3P2HY). A comprehensive literature search was conducted across PubMed, Web of Science, Cochrane Library, Scopus, and Embase databases up to December 2023. Inclusion criteria consisted of preclinical studies in animal models of EP that examined the effects of biological agents on preventing periodontal bone loss and reducing tissue inflammation. Studies were excluded if they (i) used non-EP animal models; (ii) focused on antimicrobial agents; (iii) centered on prebiotics or probiotics; (iv) evaluated compounds not classified as biologicals; or (v) included randomized clinical trials, clinical studies, or reviews. Eligibility was determined based on the PI/ECOs framework, and study quality was assessed using the SYRCLE risk-of-bias tool. Results: After screening an initial pool of 5236 records from databases, registries, and hand searches, 39 studies met the inclusion criteria. A total of 23 biological agents were evaluated across these studies. The majority of studies employed the ligature-induced model of EP to test the effectiveness of biologicals as preventive or therapeutic interventions. The dosage of biological agents and the duration of disease induction varied depending on the EP model. In all studies, the main outcome-alveolar bone loss, a hallmark of EP-was significantly inhibited by biological agents, which also reduced proinflammatory mediators when compared to untreated controls. A key strength of this review is the high number of studies included, most of which were classified as having low risk of bias. However, a notable limitation is the absence of a meta-analysis, the short follow-up periods in the included studies, and the heterogeneity among the compound dosages and route of administration. Conclusion: This systematic review demonstrates that biological agents are effective in reducing bone loss and mitigating inflammation during EP progression. Randomized clinical trials are needed to confirm these findings in human populations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Gabriela Ezequiel Oliveira et al.)

Peri-implantitis is an inflammatory condition caused by bacterial biofilms adhered on dental implant surfaces that cause progressive tissue destruction from the host's inflammatory response. The adverse effects of peri-implantitis progression can go beyond just losing the implant. This highlights the importance of implementing strategies to stabilize disease in the short term. Layer-by-layer (LbL) assembly is a promising avenue in the field of peri-implantitis management due to its applicability with a variety of substances, in addition to being an easy, versatile, and flexible process for multilayer formation to act directly in the affected site. In this Review, our objective is to offer comprehensive chemical and biological insights into the LbL system, clarifying its specific application as antimicrobial coatings, with concern for the physical site and purpose. Additionally, we delve deeper into the concepts of onset and progression of peri-implantitis, aiming to elucidate the precise indications for employing the LbL system as a coating for implant abutments in peri-implantitis treatment. Finally, we correlate the chemical composition of the LbL system with its functionality while also addressing the challenges posed by the uncontrolled environment of the oral cavity, which ultimately restricts its clinical applicability.

Congenital dental agenesis, particularly in younger adults, can have a profound impact on aesthetics and overall quality of life. The scientific literature offers various management strategies for this condition, with orthodontic movement and implant-supported rehabilitation being central to treatment. However, achieving predictable and successful outcomes necessitates a comprehensive multidisciplinary approach. Such an approach integrates diverse professional perspectives to ensure accurate diagnosis, prognosis, and treatment planning, ultimately aiming to restore dental function and address aesthetic concerns effectively. In this case report, we present the successful rehabilitation of a young patient with congenital agenesis of the mandibular central incisors. The treatment strategy combined oral surgery (extraction of deciduous teeth and autogenous bone graft), orthodontic movement (opening spaces to allow implant installation), periodontics (connective tissue graft), implantology, and prosthetic planning. We detail the specific surgical approaches employed and discuss how their integration contributed to the overall success of the case. This multidisciplinary treatment approach not only restored dental function but also met the patient's aesthetic expectations and enhanced the patient's quality of life, highlighting the importance of a coordinated approach in managing complex dental conditions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Gabriela Ezequiel Oliveira et al.)

Background/Objectives: Periodontitis (P), a chronic inflammatory condition that affects the supportive tissues around the teeth, is three to four times more prevalent in individuals with diabetes mellitus (DM), with a direct correlation between its severity and the levels of glycosylated hemoglobin (HbA1c). This study aimed to evaluate the periodontal clinical parameters following non-surgical periodontal treatment (NSPT) in P patients with or without type 2 DM. Methods : Forty patients with P were divided into two groups: Group DM/P and Group P. All the patients were assessed at baseline and at 90 and 180 days after receiving NSPT. The parameters evaluated included the HbA1c level, plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BoP). A statistical analysis was performed with a significance level set at α = 5%. Results : There were significant differences in the HbA1c levels between the DM/P and P groups at baseline, 90, and 180 days, as expected. Importantly, the HbA1c levels did not change after NSPT. Group P showed a significant reduction in both the PI and the BoP values at 90 and 180 days ( p < 0.05). In contrast, Group DM/P demonstrated a significant increase in the percentage of sites with a PPD ≥ 5 mm at 180 days ( p < 0.05). Additionally, Group P exhibited an increase in sites with a PPD ≤ 4 mm and a decrease in sites with a PPD ≥ 5 mm at both 90 and 180 days ( p < 0.05). Conclusions: Our findings suggest that DM may compromise the effectiveness of NSPT, potentially hindering favorable outcomes during the follow-up period.

This study sought to examine the effects of systemic ozone (O 3 ) treatment on the healing of skin wounds induced on the dorsal surface of Wistar rats. The skin wounds were created using a 10 mm round punch following the sagittal medial plane in 72 rats. Then, the animals were randomly assigned to four groups, each receiving the following treatments: group C, which did not undergo treatment with the O 3 /O 2 mixture; group OZ0.3, administered the O 3 /O 2 mixture at a dose of 0.3 mg/kg; group OZ0.7, given the O 3 /O 2 mixture at a dose of 0.7 mg/kg; and group OZ1.0, provided with the O 3 /O 2 mixture at a dose of 1.0 mg/kg. Six animals from each group were euthanized at 7, 14, and 21 days postoperatively. Clinical, histological, histometric, and immunohistochemical (IHC) analyses were accomplished. Data from clinical and histometric assessments revealed that OZ0.7 and OZ1.0 demonstrated more favorable healing, with greater wound contraction observed in the OZ1.0 group at 14 and 21 days. Histologically, the OZ1.0 group exhibited aspects consistent with an accelerated tissue repair process. IHC analysis revealed greater vascular endothelial growth factor (VEGF) immunostaining in the OZ0.7 (7 days) and OZ1.0 (7 and 14 days) groups compared to the C group. Expression of transforming growth factor beta-1 was significantly increased in the OZ0.7 (14 days) and OZ1.0 (7 and 14 days) groups compared to the C group. In conclusion, our data suggest that systemic use of O 3 enhanced tissue repair in cutaneous wounds in a dose-dependent manner, with concentrations of 1.0 mg/kg providing the most beneficial effects. Furthermore, the results of this study implicate the use of O 3 for the treatment of skin wounds aiming at improving the healing process over time. Our findings suggest the use of O 3 as a viable alternative to enhance wound healing and repair., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Jânderson de Medeiros Cardoso et al.)

Background: Periodontitis and diabetes mellitus (DM) exhibit a bidirectional relationship and are globally significant systemic chronic conditions. The utilization of antibiotics alongside non-surgical periodontal treatment (NSPT) has been a subject of investigation in numerous clinical studies involving human subjects. Thus, the objective of this systematic review is to address the following question: "What is the efficacy of scaling and root planing (SRP) associated with antimicrobials in patients with type 2 DM and periodontitis?". Methods: A systematic review of the literature was conducted encompassing databases such as MEDLINE/PubMed, Scopus, and Web of Science up to July 2024. Additionally, alerts were configured to capture studies published from the initial search until manuscript submission. Randomized clinical trials assessing clinical periodontal parameters in DM patients undergoing SRP and receiving either topical or systemic antibiotics were compared against a control group (SRP only). Two investigators independently screened articles, extracted data, and evaluated their quality. The selection process, study characteristics, risk of bias, impact of antibiotics on clinical parameters, and certainty of evidence were elucidated in both textual and tabular formats. Meta-analysis was performed separately with forest plots generated for treatment modalities, period of evaluation, and type of antibiotics used. Results: Following the analysis of abstracts and full articles, a total of 30 randomized clinical trials were incorporated into this review, comprising 9 studies on the association of topical antibiotics and 21 studies on systemic antibiotic administration. The principal periodontal parameters assessed included probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BoP). Conclusions: Analysis of the results led to the conclusion that adjunctive periodontal treatment with either topical or systemic antibiotics confers subtle clinical benefits. Nevertheless, owing to the heightened emergence of resistant bacteria and potential side effects, the use of antibiotic therapy in periodontal treatment should be judiciously administered.

Background and Objective: The resorption of alveolar ridge bone and maxillary sinus pneumatization are challenges to implant-supported prosthetic rehabilitation. Bone regeneration using bone substitutes and growth factors are alternatives for maxillary sinus augmentation (MSA). Therefore, we sought to evaluate the effects of the association between leukocyte and platelet-rich fibrin (L-PRF) and deproteinized bovine bone mineral (DBBM) in MSA procedures., Materials and Methods: Thirty-six maxillary sinuses from 24 individuals were included in this randomized clinical trial. The maxillary sinuses were randomly grafted with LPRF and DBBM (test group) or grafted only with DBBM (positive control). Dental implants were installed in the test group following two periods of evaluation: after 4 (DBBM+LPRF4) and 8 (DBBM+LPFR8) months of sinus graft healing, while the control group received implants only after 8 months. Cone beam computed tomography (CBCT) was taken 1 week after surgery (T1) and before implant placement (T2). Bone samples were collected during implant placement for histomorphometric and immunohistochemical (IHC) analysis. The primary implant stability was assessed by resonance frequency analysis., Results: CBCT analysis demonstrated a significant decrease in bone volume from T1 to T2 in all groups without differences among them. Histologically, the test group showed significantly increase in bone neoformation in both periods of evaluation (LPRF+DBBM4: 44.70±14.01%; LPRF+DBBM8: 46.56±12.25%) compared to the control group (32.34±9.49%). The control group showed the highest percentage of residual graft. IHC analysis showed increased staining intensity of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and runt related transcription factor 2 (RUNX-2) in LPRF+DBBM4 group, and osteopontin (OPN) in the L-PRF+DBBM8. Primary implant stability was successfully achieved (above 60 in implant stability quotient) in all the evaluated groups., Conclusion: Combination of L-PRF and DBBM increased and accelerated new bone formation allowing early implant placement probably due to the higher protein expression of RUNX2, VEGF, OCN, and OPN. These data suggest that the use of L-PRF might be an interesting alternative to use in combination with DBBM for augment the maxillary sinuses allowing the installation of appropriate length implants in shorter period of time., Clinical Relevance: This study showed improvement in bone neoformation and accelerated healing when associating L-PRF and DBBM for maxillary sinus augmentation procedures., Trial Registration: This study was registered before participant recruitment in Brazilian Registry of Clinical Trials (ReBEC - RBR-95m73t)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent evidence suggests an association between hypertension and periodontitis, although the pathways and implications underlying both chronic conditions are still poorly understood. Therefore, the aim of this study was to evaluate the relationship between hypertension and periodontitis through an observational clinical study using periodontal, physical, and biochemical analyses in hypertensive and non-hypertensive individuals with periodontitis. A total of one hundred patients were divided into two groups. The first group was hypertensive patients with periodontitis. The second group was non-hypertensive patients with periodontitis. Periodontal parameters of probing depth, bleeding on probing, and clinical attachment level were evaluated. The systolic, diastolic, mean, and differential blood pressure were measured in the physical examination. In addition, body mass index and waist-hip ratio were verified. Biochemical tests for glycated hemoglobin, fasting blood glucose, estimated blood glucose, total cholesterol, high-density lipoprotein, creatinine, glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, and C-reactive protein were evaluated. The data were submitted for statistical analysis (α = 0.05%). The results of this study demonstrated that patients with cardiovascular disease did not present with worse periodontal clinical parameters in the conditions studied. However, it is important to bear in mind that this cross-sectional study has some inherent limitations to its design; therefore, to study the relationship between hypertension and periodontitis further, an interventional randomized clinical trial should be conducted.

We sought to evaluate the effects of non-surgical periodontal treatment (NSPT) on periodontal clinical parameters, systemic blood pressure (BP), and plasma levels of systemic inflammation markers in patients with combined refractory arterial hypertension (RAH) and stage III grade B periodontitis. Twenty-seven participants with RAH and periodontitis received NSPT. The analyzed clinical parameters were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI). An assessment was performed for systemic BP, complete blood count, coagulogram, creatinine measurement, C-reactive protein (CRP), glycated hemoglobin, cholesterol, glutamic oxaloacetic transaminase, glutamate pyruvic transaminase, waist-hip ratio, and body mass index. In the follow-up period, twenty-two patients were evaluated at baseline and after 90 and 180 days. The data were submitted for statistical analysis (α = 0.05%). As expected, the clinical results showed a significant improvement in the percentages of PI, BOP, PD, and CAL, which were statistically significant at 90 and 180 days ( p < 0.0001). Importantly, NSPT significantly reduced the blood level of CRP ( p < 0.02). However, no significant reduction in BP parameters was noted in the evaluated follow-up periods. NSPT, despite the benefits in periodontal clinical parameters, reduced the plasma level of CRP but not the BP in patients with combined RAH and periodontitis.

Objective: To investigate the effect of voluntary physical activity (VPA) on inflammatory profile and the progression of experimental periodontal disease (PD) in mice., Methods: Male C57BL/6 mice were randomly distributed into Control; VPA; PD and PD/VPA groups. We registered VPA (total volume of revolutions) and average speed (revolutions/minute) in a free running wheel for 30 days. On the 15th day, animals from the PD and PD/VPA groups received ligatures on the upper second molars bilaterally. On the 30th day animals were euthanized, and PD progression was assessed by measuring alveolar bone loss (ABL - the linear distance between the cemento-enamel junction and the alveolar bone crest on the teeth buccal surface). Gene expression of RANKL (kappa nuclear factor B receptor) OPG (osteoprotegerin), IL-1β (interleukin 1 beta), IL-6 (interleukin 6) and TNF-α (tumor necrosis factor alpha) were evaluated by real-time PCR (quantitative Polymerase Chain Reaction - relative gene expression)., Results: The total volume of physical activity and the activity speed decreased along the seven days after ligature-placement (p < 0.05), returning to a similar pattern in relation to VPA group. Ligature placement produced significant bone resorption, and increased RANKL, IL-1β, IL-6 and TNF-α expression. VPA reduced ABL (p < 0,05) and the expression of TNF-α and IL-1β, whereas increased OPG expression., Conclusion: Animals induced to PD with access to the VPA wheel presented both lower gingival inflammation and less alveolar bone resorption in comparison to animals without access to the wheel., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Objectives: Many studies have been conducted to better understand the molecular mechanism involved with periodontitis progression. There has been growing interest in the potential impact of obesity on periodontitis onset and progression, but the mechanisms involved remain to be elucidated. The present study was designed to determine the impact of obesity on experimentally induced periodontitis in rats and identify novel pathways involved., Methods: Sixteen Holtzman rats were distributed into two groups (n = 8): ligature-induced periodontitis (P) and obesity plus ligature-induced periodontitis (OP). Obesity was induced by a high-fat diet for 70 days, whereas periodontitis was induced for 20 days, with a cotton thread placed around the upper first molars bilaterally. Alveolar bone loss was measured by microtomographic analysis and histologically by histometry on the hemimaxillae. The protein composition of the periodontal ligament was evaluated by proteomic analysis., Results: Data analysis (body weight, adipose tissue weight, and blood test) confirmed obesity induction, whereas bone loss was confirmed by micro-CT and histologic analyses. Proteome analysis from the periodontal ligament tissues (PDL) identified 819 proteins, 53 exclusive to the P group, 28 exclusive to the OP group, and 738 commonly expressed. Validation was performed by immunohistochemistry for selected proteins (spondin1, vinculin, and TRAP)., Conclusion: Histologically, it was found that obesity did not significantly affect bone loss resulting from periodontitis. However, the present study's findings indicated that obesity affects the proteome of PDL submitted to experimental periodontitis, allowing for identifying potential targets for personalized approaches., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic bacterial biofilm in contact with the gingival tissues initiates a cascade of inflammatory events, mediated and modulated by the host's immune response, which is characterized by increased expression of several inflammatory mediators such as cytokines and chemokines in the connective tissue. If periodontal disease (PD) is left untreated, it results in the destruction of the supporting tissues around the teeth, including periodontal ligament, cementum, and alveolar bone, which lead to a wide range of disabilities and poor quality of life, thus imposing significant burdens. This process depends on the differentiation and activity of osteoclasts, the cells responsible for reabsorbing the bone tissue. Therefore, the inhibition of differentiation or activity of these cells is a promising strategy for controlling bone resorption. Several pharmacological drugs that target osteoclasts and inflammatory cells with immunomodulatory and anti-inflammatory effects, such as bisphosphonates, anti-RANK-L antibody, strontium ranelate, cathepsin inhibitors, curcumin, flavonoids, specialized proresolving mediators, and probiotics, were already described to manage inflammatory bone resorption during experimental PD progression in preclinical studies. Meantime, a growing number of studies have described the beneficial effects of herbal products in inhibiting bone resorption in experimental PD. Therefore, this review summarizes the role of several pharmacological drugs used for PD prevention and treatment and highlights the targeted action of all those drugs with antiresorptive properties. In addition, our review provides a timely and critical appraisal for the scientific rationale use of the antiresorptive and immunomodulatory medications in preclinical studies, which will help to understand the basis for its clinical application., Competing Interests: The authors declare no conflicts of interest to report regarding the present study., (Copyright © 2022 Angelica Leticia Reis Pavanelli et al.)

Periodontal disease (PD) is a polymicrobial chronic inflammatory condition of the supporting tissues around the teeth, leading to the destruction of surrounding connective tissue. During the progression of PD, osteoclasts play a crucial role in the resorption of alveolar bone that eventually leads to the loss of teeth if the PD is left untreated. Therefore, the development of antiresorptive therapies targeting bone-resorbing cells will significantly benefit the treatment of PD. Here, we demonstrate the inhibitory effect of CsinCPI-2, a novel cysteine peptidase inhibitor from the orange tree, on periodontitis-induced inflammation, alveolar bone loss, and osteoclast differentiation. Using the ligature-induced periodontitis model in mice, we show that treatment with CsinCPI-2 (0.8 µg/g of body weight) significantly reduced inflammatory cell infiltrate in the connective tissue and prevented the loss of alveolar bone mass (BV/TV) caused by PD, effects associated with diminished numbers of TRAP-positive multinucleated cells. Furthermore, CsinCPI-2 significantly downregulated the numbers of inflammatory cells expressing CD3, CD45, MAC387, and IL-1β. In vitro, CsinCPI-2 inhibited RANKL-induced TRAP+ multinucleated osteoclast formation in mouse bone marrow macrophage cultures in a concentration-dependent manner. This effect was not due to cytotoxicity, as demonstrated by the MTT assay. CsinCPI-2 inhibited RANKL-induced mRNA expression of Acp5 , Calcr , and Ctsk , as well as the RANKL-induced upregulation of Nfatc1, a crucial transcription factor for osteoclast differentiation. Based on our findings, CsinCPI-2 prevents bone loss induced by PD by controlling the inflammatory process and acting directly on osteoclastogenesis, suggesting an interesting potential for CsinCPI-2 in the strategy for PD treatment.