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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.

Objectives: The present study aimed to compare two different models of orthodontic tooth movement (OTM) in rats by evaluating tooth movement efficiency and periodontal tissues remodelling., Design: Fifteen animals were randomly distributed into 3 groups: control group (untreated); ligature appliance (LA) as experimental OTM using a closed coil spring fixed around maxillary first molar by steel ligature; occlusal appliance (OA) as experimental OTM using a closed coil spring attached on the occlusal surface of the maxillary first molar. After 15 days, all animals were euthanized, and the maxilla of each animal was collected for qPCR, micro-computed tomography, and histological analyses., Results: Interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha gene expressions were significantly upregulated in the animals of the LA group as compared to the other groups. No significant difference was observed in tooth displacement between both methods. The LA group presented higher linear bone loss and lower values of bone volume fraction, bone mineral density, trabecular number and increased values of trabecular separation compared to the other groups. The birefringent collagen content in the tension side of the periodontal ligament contained significantly lower collagen content in the LA group than in the control group. Furthermore, on the pressure side, the collagen content was significantly lower in the LA and OA groups than in the control group., Conclusions: The OA group presented little or no deleterious effect on periodontal tissues compared to the LA group, suggesting its use may be more reliable for OTM induction in rats for 15 days., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Orthodontic movement triggers a sequence of cellular and molecular events that may be affected by different systemic conditions. This study evaluated the effect of obesity on rat periodontal tissue remodeling induced by mechanical orthodontic force., Methods: Thirty-two Holtzman rats were distributed into 4 groups: control, obesity induction (O), orthodontic movement (M), and obesity induction and orthodontic movement (OM). Obesity was induced by a high-fat diet for 90 days. After 15 days of orthodontic movement, the animals were killed. Obesity induction was confirmed by animal body weight, adipose tissue weight, and serologic analysis. Periodontal tissue remodeling was evaluated using microcomputed tomography and histologic analysis. The gene expression of adipokines and cytokines in gingival tissues was evaluated., Results: An increase in body and adipose tissue weight was observed in the obesity induction groups. The O group presented an increase in lipids and blood glucose. The OM group showed a decrease in bone volume fraction and bone mineral density compared with all other groups and a tendency for more rapid tooth movement than the M group. The OM group showed a higher quantity of inflammatory cells and higher Mmp1 expression than the O group. The O and OM groups showed higher Nampt expression than the control group and lower Nampt expression than the M group., Conclusions: Obesity modulates periodontal tissue remodeling during orthodontic movement and results in more inflammation and bone loss than in nonobese animals., (Copyright © 2020 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the present study was to evaluate the expressions of CXCL5, CXCL8, and CXCL10 in periodontal cells and tissues in response to microbial signals and/or biomechanical forces., Methods: Human gingival biopsies from inflamed and healthy sites were used to examine the chemokine expressions and protein levels by real-time PCR and immunohistochemistry. The chemokines were also investigated in gingival biopsies from rats submitted to experimental periodontitis and/or tooth movement. Furthermore, chemokine levels were determined in human periodontal fibroblasts stimulated by the periodontopathogen Fusobacterium nucleatum and/or constant tensile forces (CTS) by real-time PCR and ELISA. Additionally, gene expressions were evaluated in periodontal fibroblasts exposed to F. nucleatum and/or CTS in the presence and absence of a MAPK inhibitor by real-time PCR., Results: Increased CXCL5, CXCL8, and CXCL10 levels were observed in human and rat gingiva from sites of inflammation as compared with periodontal health. The rat experimental periodontitis caused a significant (p<0.05) increase in alveolar bone resorption, which was further enhanced when combined with tooth movement. In vitro, F. nucleatum caused a significant upregulation of CXCL5, CXCL8, and CXCL10 at 1 day. Once the cells were exposed simultaneously to F. nucleatum and CTS, the chemokines regulation was significantly enhanced. The transcriptional findings were also observed at protein level. Pre-incubation with the MEK1/2 inhibitor significantly (p<0.05) inhibited the stimulatory actions of F. nucleatum either alone or in combination with CTS on the expression levels of CXCL5, CXCL8, and CXCL10 at 1d., Conclusions: Our data provide original evidence that biomechanical strain further increases the stimulatory actions of periodontal bacteria on the expressions of these chemokines. Therefore, biomechanical loading in combination with periodontal infection may lead to stronger recruitment of immunoinflammatory cells to the periodontium, which might result in an aggravation of periodontal inflammation and destruction., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Previous studies have shown that topical application of lectin Artin-M accelerates wound healing in the rat oral mucosa. The aim of this study was to evaluate, by means of histology and immunohistochemistry (IHC) the effects of Artin-M on wound healing in the palatal mucosa in dogs. Three full thickness wounds of 6 mm diameter were surgically created in the palatal mucosa of twenty dogs and randomly divided into three groups according to one of the treatment assigned: Group C-Control (coagulum); Group A-Artin-M gel; Group V-Vehicle (carboxymethylcellulose 3%). Each animal received all the three experimental treatments. Afterwards, four animals were killed at 2, 4, 7, 14 and 21 days post-surgery. Wounded areas were photographed and scored for macroscopic evaluation. Biopsies were harvested and used for descriptive histological analysis, proliferating cell nuclear antigen IHC and measurement of myeloperoxidase activity. The results demonstrated faster wound closure in group A in comparison to the other groups in all the periods evaluated. Histological analyses exhibited improved re-epithelialization and collagen fiber formation resulting in faster maturation of granulation tissue in group A compared to the other groups by day 14. Treatment with Artin-M gel significantly induced cell proliferation and increased volumetric density of fibroblasts at day 2 and 4 (p < 0.05). Neutrophil infiltration in group A was significantly higher than the other groups (p < 0.05) at the same time points. Collectively, our findings demonstrated that Artin-M may potentially favor wound healing on palatal mucosa lesions via recruitment of neutrophils and promotion of cell proliferation.

Objective: The aim of this study was to investigate the effects of the long-term alendronate administration on bone healing in defects created in rat calvarias., Materials and Methods: Female Wistar rats were randomly distributed into 2 groups: Control (CTL): animals received saline solution once a week; and Alendronate (ALD): rats underwent alendronate treatment (1 mg/kg/weekly). After 120 days from the commencement of treatment, a critical size defect was created in all animals, and 10 animals from each group were sacrificed at 5, 10, 15, 20, 25, 30, 45 and 60-days after the defect creation. On the day of sacrifice, urine and blood samples were collected for determination of the serum levels of bone resorption and formation markers by enzyme linked immunosorbent assay, and the urinary concentration of deoxypyridinoline. Bone mineral density (BMD) in the femurs, descriptive histology, tartrate-resistant acid-phosphatase staining and immunohistochemical analyzes were assessed in the calvaria., Results: Alendronate group showed increased BMD compared to the test group. The concentration of C-terminal telopeptide of type I collagen and deoxypyridinoline decreased significantly, and the concentration of aminoterminal propeptide of procollagen type 1 and osteocalcin were significant lower in the alendronate group. Immunohistochemical analysis showed significant downregulation in the inducible nitric oxide synthase, runt-related transcription factor-2, cathepsin-K and receptor activator of nuclear factor kappa-B ligand expression in the alendronate group. Vascular endothelial growth factor and osteopontin were upregulated in the later periods of alendronate group., Conclusions: Our results suggest that long-term treatment with alendronate did not compromise the repair processing of critical size defects in rat., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to compare the periodontal tissue changes resulting from different methods of orthodontic tooth extrusion in dogs., Materials and Methods: Notches were surgically prepared in the root surface at the bone crest level of the first premolars of mongrel dogs. After 37 days, extrusion of the first lower and upper premolars was randomly performed by 3 different methods: conventional orthodontic extrusion (OE); open flap debridement performed immediately before orthodontic extrusion (OF); and orthodontic extrusion associated with weekly fiberotomy and scaling (FS). For all groups, extrusion was performed for 21 days followed by one-month retention and sacrifice. Periodontal parameters, descriptive histology, and histomorphometric analyses were performed at the end of the experimental period., Results: The median extrusion was 2.25 in the fiberotomy group, 2.0 mm in the open flap group and 1.0 mm in the orthodontic extrusion group with no significant differences between groups. The highest distance between reference notch and bone crest was observed in the fiberotomy group (p < 0.05). Histologically, radicular resorption repaired with cellular cementum was detected in all groups., Conclusions: Tooth extrusion was successfully achieved with all of the different methods of orthodontic tooth extrusion with no statistical significance between techniques. The fiberotomy approach was effective in avoiding coronal displacement of periodontal tissues. Fiberotomy associated with scaling should be indicated if the objective of the treatment is extrusion without periodontal tissue displacement., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We sought to evaluate the effects of magnesium (Mg) intake deficiency on bone metabolism in rats with induced periodontal disease (PD). Holtzman rats were randomly divided into two groups: Control - animals fed a standard diet and test - animals fed a diet with 90% Mg deficiency. After 60 days on the diets, all animals received ligature on the lower left first molars to induce PD. Animals were euthanized after 30 days following ligature placement. Blood and urine were collected for determination of serum concentrations of Mg, calcium, osteocalcin (OCN), alkaline phosphatase and parathyroid hormone (PTH) by enzyme-linked immunosorbent assay, and the urinary concentration of deoxypyridinoline (DPD). Systemic bone mineral density (BMD), bone volume and architectural bone parameters were evaluated by micro-CT in L4 lumbar vertebrae and mandible. Tartrate-resistant acid phosphatase staining and immunohistochemical (IHC) analysis of inducible nitric oxide synthase (iNOS), Runt-related transcription factor 2 (RUNX2), CD86, CD80, proliferating cell nuclear antigen, vascular endothelial growth factor, OCN and osteopontin were investigated. Reverse-transcription polymerase chain reaction was employed to assess mRNA expression of receptor-activator of nuclear factor-kB ligand, osteoprotegerin (OPG) and interleukin (IL)-6. Mg deficiency was associated with higher concentrations of PTH and DPD, and significant decrease on both systemic and mandibular BMD, as well as greater severity of alveolar and trabecular bone loss. Significant increase in osteoclasts was observed in the test group with PD. IHC analysis showed significant increase in the expression of iNOS and decreased expression of OCN and RUNX2. Increased IL-6 mRNA and decreased OPG mRNA expressions were evidenced in the test group with PD. Mg deficiency caused systemic effects indicative of altered bone metabolism in the vertebrae and affected both immune and stromal cells, aggravating inflammatory bone resorption in the ligature-induced model of periodontitis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Lipoproteins are important bacterial immunostimulating molecules capable of inducing receptor activator of nuclear factor-κB (RANKL) and osteoclast formation in vitro and in vivo . Although these molecules are present in periodontopathogenic bacteria, their role in periodontitis is not known. In this study, we used Pam2CSK4 (PAM2), a synthetic molecule that mimics bacterial lipoprotein, to investigate the effects of lipoproteins on periodontitis in mice. C57BL/6 male mice were randomly divided into three experimental groups: 1) Negative control group: animals received vehicle injection; 2) Positive control group: animals received injection of Escherichia coli lipopolysaccharide (LPS); 3) PAM2 group: animals received PAM2 injection. All the injections were performed bilaterally every other day into the palatal mucosa between first and second molars. After twenty-four days, the animals were euthanized to assess alveolar bone volume (micro-CT), cellular and extracellular composition in the gingiva (stereometric analysis), and osteoclast numbers (TRAP staining). Treatment with either PAM2 or LPS induced gingival inflammation, as demonstrated by increased infiltration of inflammatory cells and enhanced angiogenesis, associated with a smaller number of fibroblasts and decreased extracellular matrix. Importantly, treatment not only with LPS but also with PAM2 resulted in a larger number of TRAP+ multinucleated osteoclasts and significant loss of alveolar bone. Collectively, our data demonstrate that PAM2 can induce gingival inflammation and bone loss in mice, broadening the avenues of investigation into the role of lipoproteins in the pathogenesis of periodontal disease.

Resistin, a proinflammatory adipokine, is elevated in many inflammatory diseases. However, little is known about its performance in periodontitis. The present study is aimed at evaluating resistin expression and synthesis in periodontal cells and tissues under inflammatory/microbial stress in addition to its effects on the periodontium. In vivo, 24 male rats were randomly divided into two groups: control and ligature-induced periodontal disease. After 6 and 12 days, animals were sacrificed to analyze gene expression of adipokines, bone loss, inflammation, and resistin synthesis. In vitro, human periodontal ligament (PDL) fibroblasts were used to evaluate the expression of resistin after inflammatory stimuli. In addition, PDL fibroblasts were exposed to resistin to evaluate its role on soft and hard tissue metabolism markers. The periodontitis group demonstrated significant bone loss, an increase in the number of inflammatory cells and vascular structures, an increase in resistin expression and synthesis, and a decrease in the expression of adiponectin, leptin, and its functional receptor. PDL fibroblasts showed a significant increase in resistin expression and synthesis in response to the inflammatory stimulus by IL-1 β . Resistin induced an increase in cytokine expression and a decrease in the regulation of some hard tissue and matrix formation genes in PDL fibroblasts. These data indicate that resistin is produced by periodontal cells and tissues, and this effect is enhanced by inflammatory stimuli. Moreover, resistin seems to interfere with soft and hard tissue metabolism during periodontitis by reducing markers related to matrix formation and bone tissue., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Andressa V. B. Nogueira et al.)

Specialized proresolving mediators (SPRM), which arise from n-3 long-chain polyunsaturated fatty acids (n-3FA), promote resolution of inflammation and may help to prevent progression of an acute inflammatory response into chronic inflammation in patients with arthritis. Thus, this study is aimed at determining whether systemic RvE1 treatment reduces arthritis onset and severity in murine collagen-induced arthritis (CIA) and spontaneous cytokine production by human rheumatoid arthritis (RA) synovial explants. 10-week-old DBA1/J male mice were subjected to CIA and treated systemically with 0.1  μ g RvE1, 1  μ g RvE1, 5 mg/kg anti-TNF (positive control group), PBS (negative control group), or with a combination of 1  μ g of RvE1 plus 5 mg/kg anti-TNF using prophylactic or therapeutic strategies. After CIA immunization, mice were treated twice a week by RvE1 or anti-TNF for 10 days. Arthritis development was assessed by visual scoring of paw swelling and histology of ankle joints. Moreover, human RA synovial explants were incubated with 1 nM, 10 nM, or 100 nM of RvE1, and cytokine levels (IL-1 β , IL-6, IL-8, IL-10, INF- γ , and TNF- α ) were measured using Luminex bead array. CIA triggered significant inflammation in the synovial cavity, proteoglycan loss, and cartilage and bone destruction in the ankle joints of mice. Prophylactic and therapeutic RvE1 regimens did not ameliorate CIA incidence and severity. Anti-TNF treatment significantly abrogated signs of joint inflammation, bone erosion, and proteoglycan depletion, but additional RvE1 treatment did not further reduce the anti-TNF-mediated suppression of the disease. Treatment with different concentrations of RvE1 did not decrease the expression of proinflammatory cytokines in human RA synovial explants in the studied conditions. Collectively, our findings demonstrated that RvE1 treatment was not an effective approach to treat CIA in DBA1/J mice in both prophylactic and therapeutic strategies. Furthermore, no effects were noticed when human synovial explants were incubated with different concentrations of RvE1., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Rafael Scaf de Molon et al.)

The association between rheumatoid arthritis (RA) and periodontal disease (PD) has been the focus of numerous investigations driven by their common pathological features. RA is an autoimmune disease characterized by chronic inflammation, the production of anti-citrullinated proteins antibodies (ACPA) leading to synovial joint inflammation and destruction. PD is a chronic inflammatory condition associated with a dysbiotic microbial biofilm affecting the supporting tissues around the teeth leading to the destruction of mineralized and non-mineralized connective tissues. Chronic inflammation associated with both RA and PD is similar in the predominant adaptive immune phenotype, in the imbalance between pro- and anti-inflammatory cytokines and in the role of smoking and genetic background as risk factors. Structural damage that occurs in consequence of chronic inflammation is the ultimate cause of loss of function and disability observed with the progression of RA and PD. Interestingly, the periodontal pathogen Porphyromonas gingivalis has been implicated in the generation of ACPA in RA patients, suggesting a direct biological intersection between PD and RA. However, more studies are warranted to confirm this link, elucidate potential mechanisms involved, and ascertain temporal associations between RA and PD. This review is mainly focused on recent clinical and translational research intends to discuss and provide an overview of the relationship between RA and PD, exploring the similarities in the immune-pathological aspects and the possible mechanisms linking the development and progression of both diseases. In addition, the current available treatments targeting both RA and PD were revised.

This study was performed to investigate sinus floor augmentation with two different particle sizes of demineralized bovine bone mineral (DBBM) by means of histological and immunohistochemical (IHC) analysis. A randomized clinical trial was conducted involving 10 individuals requiring two-stage bilateral maxillary sinus augmentation for implant installation. The patients were randomly divided into two groups following a split-mouth design: the maxillary sinus on one side was filled with small-sized particles (0.25-1mm) and on the contralateral side with large-sized particles (1-2mm). After a healing period of 8 months, 25 implants were placed. During implant site preparation, bone biopsies were obtained from each sinus, perpendicular to the long axis of the implant (buccal-palatal direction), for descriptive and histomorphometric analyses. IHC staining for protein expression of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and tartrate-resistant acid phosphatase (TRAP) was also performed. Histomorphometric analysis revealed no statistically significant difference in the percentage of biomaterial (32.4±8.56% and 38.0±6.92%), newly formed bone (36.1±9.60% and 36.7±5.79%), or connective tissue (30.4±8.63% and 23.8±6.16%) between the small- and large-sized particle groups, respectively. IHC analysis did not reveal differences in the expression of OCN, VEGF, or TRAP. These findings suggest that both particle sizes of DBBM are effective for bone augmentation in the maxillary sinus., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate bone turnover alterations after alendronate (ALD) withdrawal and its influence on dental implants osseointegration., Materials and Methods: Seventy female Wistar rats were randomly divided in 2 groups that received on day 0 either placebo (control group-CTL; n = 10) or 1 mg/kg sodium alendronate (ALD; n = 60) once a week for 4 months. At day 120, ALD treatment was suspended for 50 animals. Then, a titanium implant was placed in the left tibia of each rat that were randomly allocated in five subgroups of ten animals each, according to the period of evaluation: day 0 (INT-0), day 7 (INT-7), day 14 (INT-14), day 28 (INT-28), and day 45 (INT-45) after ALD withdrawal. CTL group and a group that received ALD until the end of the experimental period (non-interrupted group-non-INT; n = 10) underwent implant placement on day 120. Animals were euthanized 28 days after implant surgery. Bone mineral density (BMD) of femur and lumbar vertebrae were evaluated by DXA, biochemical markers of bone turnover were analyzed by ELISA, and bone histomorphometry was performed to measure bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO)., Results: All groups receiving ALD showed higher BMD values when compared to CTL group, which were maintained after its withdrawal. Decreased concentrations in all bone turnover markers were observed in the non-INT group, and in the groups in which ALD was discontinued compared to the CTL group. The non-INT group showed lower %BIC and notably changes in bone quality, which was persistent after drug withdrawal., Conclusion: Collectively, the findings of this study demonstrated that ALD therapy decreased bone turnover and impaired bone quality and quantity around dental implants, and that its discontinuation did not reverse these findings., Clinical Relevance: The severe suppression of bone turnover caused by the prolonged use of ALD may alter the capacity of bone tissue to integrate with the implant threads impairing the osseointegration process.

Purpose: To investigate the effectiveness of adding leukocyte and platelet-rich fibrin (L-PRF) to deproteinized bovine bone mineral (DBBM) for early implant placement after maxillary sinus augmentation., Materials and Methods: Twelve patients requiring two-stage bilateral maxillary sinus augmentation were enrolled to the study. The elevated sinus cavities were randomly grafted with DBBM + L-PRF (test) or DBBM alone (control) in a split-mouth design. Implants were placed in the augmented sites after 4 months in the test group and 8 months in the control group. Bone biopsies were collected during implant placement for histomorphometric evaluation. Resonance frequency analysis was performed immediately after implant placement and at implant loading in both groups. Cone-beam computed tomography was obtained preoperatively and postoperatively for evaluation of graft volume changes., Results: Both procedures were effective for maxillary sinus augmentation. Cone-beam computed tomography analysis did not reveal differences in graft volume between test and control group at any of the evaluated time points (P > .05). Histological evaluation demonstrated increased percentage of newly formed bone for the test group (44.58% ± 13.9%) compared to the control group (30.02% ± 8.42%; P = .0087). The amount of residual graft in the control group was significantly higher (13.75% ± 9.99%) than in the test group (3.59 ± 4.22; P = .0111). Implant stability quotient (ISQ) immediately after implant placement was significantly higher in the control group (75.13 ± 5.69) compared to the test group (60.9 ± 9.35; P = .0003). The ISQ values at loading did not differ between the groups (P = .8587). Implant survival rate was 100% for both groups., Conclusion: The addition of L-PRF to the DBBM into the maxillary sinus allowed early implant placement (4 months) with increased new bone formation than DBBM alone after 8 months of healing., (© 2019 Wiley Periodicals, Inc.)

We sought to better characterize the progression of periodontal tissue breakdown in rats induced by a ligature model of experimental periodontal disease (PD). A total of 60 male Sprague-Dawley rats were evenly divided into an untreated control group and a PD group induced by ligature bilaterally around first and second maxillary molars. Animals were sacrificed at 1, 3, 5, 7, 14, and 21 days after the induction of PD. Alveolar bone loss was evaluated by histomorphometry and microcomputed tomography (μCT). The immune-inflammatory process in the periodontal tissue was assessed using descriptive histologic analysis and quantitative polymerase chain reaction (qPCR). This ligature model resulted in significant alveolar bone loss and increased inflammatory process of the periodontal tissues during the initial periods of evaluation (0-14 days). A significant increase in the gene expression of pro-inflammatory cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and proteins involved in osteoclastogenesis, receptor activator of nuclear factor-k B ligand (RANKL) and osteoprotegerin (OPG) was observed in the first week of analysis. In the later periods of evaluation (14-21 days), no significant alterations were noted with regard to inflammatory processes, bone resorption, and expression of cytokine genes. The ligature-induced PD model resulted in progressive alveolar bone resorption with two different phases: Acute (0-14 days), characterized by inflammation and rapid bone resorption, and chronic (14-21 days) with no significant progression of bone loss. Furthermore, the gene expressions of IL-6, IL-1β, TNF-α, RANKL, and OPG were highly increased during the progress of PD in the early periods. RESEARCH HIGHLIGHTS: Ligature-induced bone resorption in rats occurred in the initial periods after disease induction The bone resorption was characterized by two distinct phases: Acute (0-14 days), with pronounced inflammation and alveolar bone loss Chronic phase (14-21 days): No further disease progression Several pro-inflammatory cytokines were increased during the progress of periodontitis., (© 2018 Wiley Periodicals, Inc.)

Interleukin-33 (IL-33) and its receptor, ST2, are implicated in bone remodeling. The lack of estrogen after menopause results in an accelerated bone loss. Here we investigated the role of ST2 in the bone loss induced by estrogen deficiency. ST2-deficient mice (ST2 -/- ) and their littermates (wildtype [WT]) were ovariectomized (OVX), while ovary-intact mice were used as controls. Bone sites were analyzed by microcomputed tomography, histomorphometry, and quantitative real-time polymerase chain reaction (qPCR). Deletion of IL-33 or ST2 resulted in a similar bone loss in the femur and maxilla. Ovariectomy in WT mice caused bone loss in the same areas. The lack of ST2 in OVX mice did not alter bone remodeling in the femur but prevented bone loss in the maxilla. Consistently, ovariectomy increased the IL-33 messenger RNA (mRNA) levels in the maxilla but not in the femur. Under mechanical stimulation, ovariectomy and ST2 deletion independently increased bone remodeling induced by orthodontic tooth movement, which was also associated with a greater number of osteoclasts and a reduced number of osteoblasts in the maxillary bone. ST2 -/- OVX mice, however, displayed twice as many osteoblasts as that of WT OVX mice. Ovariectomy and ST2 deletion differently altered the cytokine mRNA levels in the maxilla. Remarkably, interleukin-10 expression was decreased in both WT OVX and ST2 -/- mice, and this reduction was completely restored in ST2 -/- OVX mice. The results demonstrate that estrogen and IL33/ST2 independently protect against bone loss. However, the ovariectomy-induced bone loss is IL-33/ST2-dependent in the maxilla but not in the femur, indicating a bimodal and site-specific role of ST2 in bone remodeling., (© 2018 Wiley Periodicals, Inc.)

Purpose: The objective of this investigation was to assess the microbiologic contamination in the inner surface of titanium implants prior to prosthetic abutment placement., Materials and Methods: The study population consisted of partially edentulous individuals who had previously received at least one internal hexagon titanium dental implant. A bacterial sample of the inner surface of the individual dental implant was taken after surgical reopening for healing abutment placement. The samples were allocated in order to evaluate three distinctive variables as follows: (1) location (mandible vs maxilla), (2) early exposure of implants to the oral cavity (cover screw) throughout the healing stage (exposed vs not exposed), and (3) existence or lack of keratinized mucosa (KM). The microorganism species detected were examined by checkerboard DNA-DNA hybridization., Results: A total of 32 partially edentulous patients with 78 implants placed in both the maxilla and mandible were enrolled: 8 men and 24 women, ranging in age from 27 to 64 years (mean age: 47.7 years). Bacteria were detected in 20 patients, distributed in 41 implants. Spontaneous early implant exposure and absence of KM did not increase bacterial contamination in the inner surface of implants. A significant increase in the detection of 22 bacterial species was found in the mandible when compared with the maxilla., Conclusion: Microbial biofilm accumulation in the implant's internal surface might happen before healing abutment placement. Exposure of implants to the oral cavity and absence of KM were not directly related to a greater microbial biofilm count. The results suggested that submerged healing does not protect implants against bacterial colonization.

This case report aimed to describe the effects of leukocyte and platelet-rich fibrin (L-PRF) associated with demineralized bovine bone mineral (DBBM) and absorbable collagen membrane (CM) on bone regeneration in maxillary sinus augmentation. A 59-year-old male patient was referred to the Department of Periodontology for implant rehabilitation of his edentulous upper jaw. The treatment plan involved maxillary sinus augmentation followed by implant installations. A split-mouth design was employed in which the right maxillary sinus was filled using L-PRF, DBBM, and CM; the left side was filled with DBBM and CM. After 4 and 8 months postoperatively, 2 dental implants were installed in each of the right and left maxillary sinuses. Cone-beam computerized tomography (CBCT) was taken before and after sinus augmentation for evaluation of tridimensional bone volume alterations. Bone biopsies were harvested from the implant sites for histomorphometric evaluation. Resonance frequency analysis was employed immediately after implant placement and before prosthetic rehabilitation for evaluation of implant stability. Implants were loaded 10 months after sinus augmentation. CBCT analysis showed a higher resorption rate in the right side of the maxillary sinus (L-PRF + DBBM) compared to the left side (22.25% and 8.95%, respectively). Implant stability quotients were above 68 in all time-points for both groups. Histomorphometric analysis showed a high amount of newly formed bone when L-PRF was used compared with DBBM alone (2 118 102 and 975 535 mm 3 , respectively). Taken together, both techniques were effective for maxillary sinus augmentation, however the addition of L-PRF to the graft allowed early implant placement and accelerated bone healing in the conditions studied.

Purpose: The objective of this investigation was to assess vertical bone augmentation using deproteinized bovine bone mineral (DBBM) infused or not with recombinant human bone morphogenetic protein (rhBMP-2) in rabbit tibiae., Materials and Methods: A total of 18 female rabbits (New Zealand) received two blocks of DBBM in each tibia. The DBBM blocks were randomly assigned into four experimental groups: DBBM (only the bone graft); DBBM associated with absorbable collagen sponge (ACS); DBBM plus rhBMP-2 (1.5 mg/mL); and DBBM infused with rhBMP-2 (1.5 mg/mL) in an ACS carrier. Animals were sacrificed after 12 weeks, and the tibiae containing the DBBM blocks were dissected and analyzed radiographically (microcomputed tomography [micro-CT]), histologically, and immunohistochemically., Results: Micro-CT analysis showed a considerable increase in bone volume (BV) and BV/tissue volume in the rhBMP-2/ACS group compared with all the others. Trabeculae thickness also increased in the rhBMP-2/ACS group compared with the DBBM/ACS group. Trabecular number, separation, and bone mineral density were not different among groups. Histomorphometric evaluation showed increased newly formed bone in the rhBMP-2/ACS group compared with the DBBM and DBBM/ACS groups. The amount of residual bone graft was statistically higher in the rhBMP-2 groups compared with the DBBM/ACS group. Immunohistochemical analysis showed that the vascular endothelial growth factor (VEGF) expression was more intense in the rhBMP-2/ACS group compared with the DBBM/ACS group. The immunopositivity for type 1 collagen tended to be higher in the two groups with rhBMP-2., Conclusion: Collectively, the results of this study suggest that the addition of rhBMP-2 in an ACS carrier placed on top of the DBBM graft enhanced bone formation in this animal model.

Aim: The aim of this nonrandomized controlled preliminary clinical trial was to compare treatment using short and conventional implants in the posterior region of the mandible after prosthesis installation by means of clinical, resonance frequency, and radiographic analyses., Materials and Methods: A total of 10 patients with 40 dental implants already installed were included in this study. Four implants were installed for each subject, in which the length of the implants (short and conventional) was distributed according to the reminiscent alveolar bone in the left and right side of the mandible. All implants received splinted prosthesis after the osseointegration period. Analyses were performed immediately after prosthesis installation (T1), and 3 (T2) and 6 months (T3) after prosthesis placement., Results: The 6-month survival and success rates were 100% for the short and conventional implants. Probing depths (PDs) after 6 months did not show statistical differences between short and conventional implants. All groups showed mean implant stability quotient (ISQ) values above 60 in all periods evaluated, demonstrating great implant stability, and no differences were found between groups at T3. Radiographic measurements showed an increased bone loss for conventional implants compared with short implants in all the three periods evaluated., Conclusion: Our findings suggest that treatment of resorbed posterior regions in the mandible with shorter dental implants is as reliable as treatment with conventional implants after 6 months of splinted prosthesis installation., Clinical Significance: Short implants might be considered a predictable treatment alternative to bone augmentation or extensive surgical techniques in regions of restricted vertical bone height in the posterior region of the mandible.

The aim of this study was to investigate the effect of cyclosporine A (CsA) therapy on bone healing around osseointegrated implants in the rabbit by means of descriptive histologic and histomorphometric analyses. Eighteen rabbits received one implant each in the right tibia proximal metaphysis. After the bone-healing period of 3 months, 6 randomly selected animals were sacrificed (Group CTL-12) before the immunosuppression therapy initiation to obtain a standard of implant integration. Another six randomly selected animals were submitted to a daily subcutaneous (sc) injection of 10 mg/kg CsA (Group CsA) whereas the six remaining animals received daily sc injections of saline solution (Group CTL-24). Groups CTL-24 and CsA were sacrificed after another 12 weeks. Bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) within the implant threads were measured. Bone density (BD) and descriptive histological analyses were also accomplished. Rabbits under CsA therapy presented statistically lower percentage of BIC (33.28 ± 6.19) compared to the animals of CLT-24 (55.6 ± 17.73). No differences were found between CsA and CTL-12 (38.7 ± 7.87). Significant decreased percentage of BAFO between the implant threads in the CsA (48.43 ± 9.48) group compared to the CTL-24 (72.26 ± 11.72) was observed. No differences were found between CsA and CTL-12 (61.99 ± 13.94) groups. BD analysis showed significant lower BD in the CsA (48.56 ± 9.32) group compared to the CTL-12 (68.74 ± 10.89) and CTL-24 (77.96 ± 4.96) groups. Collectively, our findings demonstrated that CsA therapy negatively affect the bone healing around osseointegrated implants due to the significant lower values for BIC, BAFO, and BD., (© 2017 Wiley Periodicals, Inc.)

Objective: We aimed to assess the surfaces of commercially pure titanium implants (cp Ti) with modified surfaces by laser beam (LS) with and without hydroxyapatite (HA) deposition, without (HAB) and with (HABT) thermal treatment. Furthermore, we have compared them with implants with surfaces modified by acid treatment (AS) and with machined surfaces (MS) utilizing histomorphometric and descriptive histologic analyses., Material and Methods: Surface topography characterization was analyzed by scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDX), and surface roughness (Ra) before implant installation. Forty-five rabbits received seventy-five implants in their left and right tibias and were randomly divided into five groups (n = 5 implants per group): (1) cp Ti implant modified by LS, (2) cp Ti implant modified by laser beam associated with HA deposition without heat treatment (HAB), (3) cp Ti implant modified by laser beam associated with HA deposition with heat treatment (HABT), (4) cp Ti implant with modified surface by means of acid treatment (Master Porous) commercially available (AS), and (5) cp Ti implant with MS commercially available. After 30, 60, and 90 days, the animals were euthanized and the implants and surrounding bone were removed and prepared by a non-decalcified histological process. The percentage of bone-to-implant contact (BIC) and the bone area fraction occupancy (BAFO) between the first three threads was evaluated to the higher cortical region., Results: BIC (%) was statistically superior (p < 0.001) on the LS (69.36 ± 7.91, 71.67 ± 8.79, and 79.69 ± 3.3), HAB (73.22 ± 3.75, 69.48 ± 1.89, and 75.7 ± 4.62), and HABT (65.41 ± 5.51, 71.3 ± 2.5, and 79.68 ± 5.01) compared with AS (49.15 ± 5.76, 41.94 ± 2.85, and 57.18 ± 7.81) and MS (36.69 ± 7.24, 52.52 ± 2.75, and 51.31 ± 6.96) in the 30, 60, and 90-day periods, respectively. BAFO (%) of HAB at 30 days (90.17 ± 6.24) was statistically superior (p < 0.01) to all the other groups. At 60 and 90 days, BAFO of LS (87.17 ± 5.9 and 87.99 ± 2.52), HAB (85.95 ± 3.93 and 82.17 ± 3.65), and HABT (83.27 ± 1.44 and 88.67 ± 2.67) was higher than the AS (77.49 ± 5.83 and 76.42 ± 5.98) and MS (74.01 ± 4.68 and 73.81 ± 4.91)., Conclusions: Collectively, our data indicate that the modified surfaces LS, HAB, and HABT favored the interaction between bone and implant and increased bone formation. In addition, HAB showed higher biological behavior favoring the osseointegration., Clinical Relevance: Our study provides evidence that LS, HAB, and HABT-modified surfaces improved bone-to-implant contact and increased bone formation around osseointegrated implants compared to conventional machined implants favoring the osseointegration process.

Aim: This study aimed to evaluate the contribution of biomechanical loading to inflammation-induced tissue destruction., Materials and Methods: A total of 144 adult Holtzman rats were randomly assigned into four experimental groups: control (C), ligature-induced periodontal disease (P), orthodontic movement (OM), and combination group (OMP). On days 1, 3, 7, and 15, following baseline, nine animals from each experimental group were killed. Bone volume fraction (BVF) and bone mineral density (BMD) were measured using micro-computed tomography. Expression and synthesis profile of cytokines and receptors of inflammation in gingival tissues were evaluated by PCR array assay and multiplex immunoassay., Results: At 15 days, the OMP group presented a significantly (p < 0.05) lower BVF and BMD levels when compared to all the other groups. The OMP group presented the highest number of upregulated protein targets in comparison to the other groups. Furthermore, the gene expression and protein levels of CCL2, CCL3, IL-1β, IL1-α, IL-18, TNF-α, and VEGF were significantly (p < 0.05) higher in the OMP group when compared to the P group., Conclusions: In summary, mechanical loading modulates the inflammatory response of periodontal tissues to periodontal disease by increasing the expression of several pro-inflammatory mediators and receptors, which leads to increased bone resorption., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this study was to compare implant stability after maxillary sinus floor augmentation using small- or large-sized particles of Bio-Oss. Ten partially edentulous patients requiring bilateral maxillary sinus floor augmentation were enrolled. The subjects were assigned randomly to one of two experimental groups: maxillary sinus was filled with 0.25-1mm particle size (small particles) and the contralateral side was filled with 1-2mm particle size (large particles). After 8 months, a total of 25 implants were placed in the two maxillary sinuses. Primary implant stability was measured immediately after implant placement (T0) using a torque controller and resonance frequency analysis (RFA). Six months after implant placement (T1), the implant stability was measured again. There were no postoperative complications in either particle size group, and the success rate for implant survival was 100%. All implants showed good primary stability as evidenced by high torque for the implant insertion in both groups. RFA revealed high ISQ values for all implants installed in both groups at T0 and T1. These results indicate that the size of the Bio-Oss particles (small and large) did not influence implant stability in the maxillary sinus. Indeed, small and large particles of Bio-Oss presented optimal properties, supporting their possible use as osteoconductive grafts., (Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Two cases of aesthetic implant abutment rehabilitation in the maxillary anterior area in periodontally compromised patients following conventional periodontal therapy and tooth extractions are presented. For the two cases of anterior tooth loss due to advanced periodontal disease progression, atraumatic flapless extractions were performed followed by the placement of immediate implants and provisional restorations. For the first case, lithium disilicate cemented over the abutment was used to achieve excellent aesthetic results. In the second case, custom zirconia abutments were used as prosthetic components. The results at the 3-year follow-up showed absence of inflammation and/or infection on the peri-implantar tissue with satisfactory aesthetic and excellent biological and clinical results achieved with reduced treatment time and morbidity for both patients. Total absence of infection and frequent plaque control after implant placement are mandatory before selection of the abutment material. The planning of the final treatment as specified by the concept of comprehensive dental care is outlined, and the final outcome is discussed in relation to the literature., (Copyright© by the International Academy of Periodontology.)

Osteonecrosis of the jaws (ONJ) is a complication of antiresorptive medications, such as denosumab or bisphosphonates, prescribed to patients with bone malignancy or osteoporosis. The most common instigating local factor in ONJ pathogenesis is tooth extraction. However, in adults the great majority of teeth are extracted due to dental disease. Here, we have investigated alveolar bone healing after extraction of healthy teeth or teeth with naturally occurring periradicular disease in mice treated with high dose zoledronic acid (ZA), a potent bisphosphonate, or OPG-Fc, a RANKL inhibitor. C57BL/6 mice were treated for eight weeks and in vivo micro-CT was performed to identify spontaneously occurring periradicular lesions around the roots of maxillary molars. Then, extractions of molars with and without dental disease were performed in all groups. Four weeks later, animals were euthanized and maxillae were dissected and analyzed. Clinically, all vehicle animals with extraction of healthy or diseased teeth, and most OPG-Fc or ZA animals with extraction of healthy teeth showed normal mucosal healing. On the contrary, most animals with OPG-Fc or ZA treatment and extraction of diseased teeth demonstrated impaired healing with visible mucosal defects. Radiographically, bone socket healing was significantly compromised in OPG-Fc and ZA-treated mice with periradicular disease in comparison to other groups. Histologically, all vehicle animals showed normal mucosal healing and socket remodeling. OPG-Fc and ZA animals with extraction of healthy teeth showed normal mucosal healing, woven bone formation in the socket, and decreased remodeling of the original socket confines. OPG-Fc and ZA animals with extraction of diseased teeth showed mucosal defects, persistent prominent inflammatory infiltrate, bone exposure and areas of osteonecrosis. These findings support that dental disease is critical in the pathogenesis of ONJ, not only as the instigating cause for tooth extraction, but also as a compounding factor in ONJ development and pathophysiology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J mice were divided into four groups: control, zoledronic acid (ZA), collagen-induced arthritis (CIA), and CIA-ZA. Animals were pretreated with vehicle or ZA. Bovine collagen II emulsified in Freund's adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8 weeks. ONJ indices were measured by micro-CT (µCT) and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by µCT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, periodontal ligament (PDL) space widening, lamina dura loss, and cortex thinning. ZA prevented these changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Objective: To evaluate in long-term periods the destruction of periodontal tissues and bacterial colonization induced by oral gavage with periodontopathogens or ligature experimental periodontal disease models., Material and Methods: Forty-eight C57BL/6 J mice were divided into four groups: group C: negative control; group L: ligature; group G-Pg: oral gavage with Porphyromonas gingivalis; and group G-PgFn: oral gavage with Porphyromonas gingivalis associated with Fusobacterium nucleatum. Mice were infected by oral gavage five times in 2-day intervals. After 45 and 60 days, animals were sacrificed and the immune-inflammatory response in the periodontal tissue was assessed by stereometric analysis. The alveolar bone loss was evaluated by live microcomputed tomography and histometric analysis. qPCR was used to confirm the bacterial colonization in all the groups. Data were analyzed using the Kruskal-Wallis, Wilcoxon, and ANOVA tests, at 5 % of significance level., Results: Ligature model induced inflammation and bone resorption characterized by increased number of inflammatory cells and decreased number of fibroblasts, followed by advanced alveolar bone loss at 45 and 60 days (p < 0.05). Bacterial colonization in groups G-Pg and G-PgFn was confirmed by qPCR but inflammation and bone resorption were not observed (p < 0.05)., Conclusions: The ligature model but not the oral gavage models were effective to induce inflammation and bone loss in long-term periods. Pg colonization was observed in all models of experimental periodontal disease induction, independent of tissue alterations. These mice models of periodontitis validates, compliments, and enhances published PD models that utilize ligature or oral gavage and supports the importance of a successful colonization of a susceptible host, a bacterial invasion into vulnerable tissue, and host-bacterial interactions that lead to tissue destruction., Clinical Relevance: The ligature model was an effective approach to induce inflammation and bone loss similar to human periodontitis, but the oral gavage models were not efficient in inducing periodontal inflammation and tissue destruction in the conditions studied. Ligature models can provide a basis for future interventional studies that contribute to the understanding of the disease pathogenesis and the complex host response to microbial challenge.

Purpose: We sought to evaluate the effectiveness of bone substitutes in circumferential peri-implant defects created in the rabbit tibia., Methods: Thirty rabbits received 45 implants in their left and right tibia. A circumferential bone defect (6.1 mm in diameter/4 mm depth) was created in each rabbit tibia using a trephine bur. A dental implant (4.1 mm × 8.5 mm) was installed after the creation of the defect, providing a 2-mm gap. The bone defect gaps between the implant and the bone were randomly filled according to the following groups: blood clot (CO), particulate Bio-Oss(®) (BI), and Bio-Oss(®) Collagen (BC). Ten animals were euthanized after periods of 15, 30, and 60 days. Biomechanical analysis by means of the removal torque of the implants, as well as histologic and immunohistochemical analyses for protein expression of osteocalcin (OC), Runx2, OPG, RANKL, and TRAP were evaluated., Results: For biomechanics, BC showed a better biological response (61.00±15.28 Ncm) than CO (31.60±14.38 Ncm) at 30 days. Immunohistochemical analysis showed significantly different OC expression in CO and BC at 15 days, and also between the CO and BI groups, and between the CO and BC groups at 60 days. After 15 days, Runx2 expression was significantly different in the BI group compared to the CO and BC groups. RANKL expression was significantly different in the BI and CO groups and between the BI and BC groups at 15 days, and also between the BI and CO groups at 60 days. OPG expression was significantly higher at 60 days postoperatively in the BI group than the CO group., Conclusions: Collectively, our data indicate that, compared to CO and BI, BC offered better bone healing, which was characterized by greater RUNX2, OC, and OPG immunolabeling, and required greater reversal torque for implant removal. Indeed, along with BI, BC presents promising biomechanical and biological properties supporting its possible use in osteoconductive grafts for filling peri-implant gaps.

Surface attachment is the first step in biofilm formation, and the ability of bacteria to adhere to surfaces and develop a biofilm is directly influenced by electrostatic interactions between the bacteria and the chemical composition of material surfaces. Here, we investigated the influence of physical and chemical characteristics of titanium (Ti) and zirconia (ZrO2) as implant abutment surfaces on the bacterial adhesion phase and compared the results to bovine enamel (BE) simulating a human tooth. To achieve this goal, we used 2 common pathogens of the oral cavity, Streptococcus mutans UA140 and Porphyromonas gingivalis 33277. To investigate the influence of material surfaces on bacterial adhesion, we studied the surface free energy as well as the topography by atomic force microscopy, and the chemical elements composition by scanning electron microscopy equipped with an energy dispersive X-ray spectroscope. Our results indicated a hydrophobic characteristic for all of the materials; however, the presence of polar and nonpolar components could aid in understanding why greater numbers of bacteria had adhered to BE compared to the other surfaces. Our confocal microscopy data support the proposition that electrostatic interactions, indeed, affected the initial adhesion phase. Within the limitations of a laboratory study, the results revealed bacterial adhered on BE and no bacteria could be observed by confocal images on Ti and ZrO2 implant abutment surfaces.

Background: A positive association between obesity-associated metabolic disorders (e.g., hyperlipidemia and diabetes) and periodontitis has been demonstrated in the literature. This study evaluates the role of cafeteria diet-induced obesity/hyperlipidemia (CAF) on alveolar bone loss (ABL) in rats., Methods: Sixty male Wistar rats were randomly divided in four groups: control, periodontitis (PERIO), obesity/hyperlipidemia (CAF), and obesity/hyperlipidemia plus periodontitis (CAF+PERIO). Groups CAF and CAF+PERIO were exposed to a high-fat, hypercaloric diet. At week 12, periodontal disease was induced in groups PERIO and CAF+PERIO by ligatures in the upper second molar. The contralateral tooth was considered the intragroup control. Body weight and Lee index were evaluated weekly during the experiment. Serum glucose and cholesterol/triglycerides in the liver were evaluated, and percentage of ABL was measured by microcomputed tomography. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β were evaluated by enzyme-linked immunosorbent assay at week 17., Results: Body weight, Lee index, and cholesterol/triglycerides in the liver increased in groups exposed to the cafeteria diet. Groups PERIO and CAF+PERIO exhibited a significantly higher ABL compared to control and CAF groups. The presence of obesity and hyperlipidemia significantly increased ABL in the CAF+PERIO group compared to the PERIO group (53.60 ± 3.44 versus 42.78 ± 7.27, respectively) in the sides with ligature. Groups exposed to CAF exhibited higher ABL in the sides without ligature. No differences were observed among groups for IL-1β and TNF-α., Conclusion: Obesity and hyperlipidemia modulate the host response to challenges in the periodontium, increasing the expression of periodontal breakdown.

Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by μCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a "drug holiday" in managing the ONJ patient., Competing Interests: All other authors state that they do not have any conflicts of interest., (© 2015 American Society for Bone and Mineral Research.)

Objective: The aim of this clinical report was to reestablish the buccal bone wall after immediate implant placement. The socket defect was corrected with autogenous bone, and a connective tissue graft was removed from the maxillary tuberosity to increase the thickness, height, and width of the buccal bone and gingival tissue followed by immediate provisionalization of the crown during the same operation., Clinical Considerations: A 66-year-old patient presented with a hopeless maxillary left central incisor with loss of the buccal bone wall. Atraumatic, flapless extraction was performed, and an immediate implant was placed in the extraction socket followed by preparation of an immediate provisional restoration. Subsequently, immediate reconstruction of the buccal bone plate was performed, using the tuberosity as the donor site, to obtain block bone and connective tissue grafts, as well as particulate bone. Finally, immediate provisionalization of the crown followed by simple sutures was performed. Cone-beam computed tomography and periapical radiographs were taken before and after surgery. After 4 months, the final prosthetic crown was made. After a 2-year follow-up, a satisfactory aesthetic result was achieved with lower treatment time and morbidity., Conclusion: This case demonstrates the effective use of immediate reconstruction of the buccal bone wall for the treatment of a hopeless tooth in the maxillary aesthetic area. This procedure efficiently promoted harmonious gingival and bone architecture, recovered lost anatomical structures with sufficient width and thickness, and maintained the stability of the alveolar bone crest in a single procedure., Clinical Significance: If appropriate clinical conditions exist, immediate dentoalveolar restoration may be the most conservative means of reconstructing the buccal bone wall after immediate implant placement followed by immediate provisionalization with predictable healing and lower treatment time., (© 2015 Wiley Periodicals, Inc.)