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AIM: To reveal the heterogeneity of ex vivo-cultured human mesenchymal stromal cells derived from either masticatory or lining oral mucosa. MATERIALS AND METHODS: Cells were retrieved from the lamina propria of the hard palate and alveolar mucosa of three individuals. The analysis of transcriptomic-level differences was accomplished using single-cell RNA sequencing. RESULTS: Cluster analysis clearly distinguished between cells from the masticatory and lining oral mucosa, and revealed 11 distinct cell sub-populations, annotated as fibroblasts, smooth muscle cells or mesenchymal stem cells. Interestingly, cells presenting a mesenchymal stem cell-like gene expression pattern were predominantly found in masticatory mucosa. Although cells of masticatory mucosa origin were highly enriched for biological processes associated with wound healing, those from the lining oral mucosa were highly enriched for biological processes associated with the regulation of epithelial cells. CONCLUSIONS: Our previous work had shown that cells from the lining and masticatory oral mucosae are phenotypically heterogeneous. Here, we extend these findings to show that these changes are not the result of differences in averages but rather represent two distinct cell populations, with mesenchymal stem cells more common in masticatory mucosa. These features may contribute to specific physiological functions and have relevance for potential therapeutic interventions.
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Células-Tronco Mesenquimais , Transcriptoma , Humanos , Mucosa Bucal , Células Epiteliais , CicatrizaçãoRESUMO
OBJECTIVES: We previously showed that accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated here its effect on the number of macrophages and endothelial cells (ECs) within the CM as a possible mechanism for inhibition of CM resorption. MATERIALS AND METHODS: Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS, and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and transglutaminase II, respectively. RESULTS: Diabetes increased the number of macrophages and ECs within the CMs (â¼2.5-fold and fourfold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p < 0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. CONCLUSIONS: Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals. CLINICAL RELEVANCE: The combination of CLHA and CM may represent a valuable approach when guided tissue regeneration or guided bone regeneration procedures are performed in diabetic patients.
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Diabetes Mellitus Experimental , Ácido Hialurônico , Animais , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Células Endoteliais , Humanos , Ácido Hialurônico/farmacologia , Macrófagos/metabolismo , Ratos , Ratos WistarRESUMO
AIMS: To compare the gene expression profiles and proliferation rates of fibroblasts from the oral lining and masticatory mucosae. MATERIALS AND METHODS: Primary human fibroblasts were retrieved from the posterior masticatory hard palate and the lining alveolar mucosa of five individuals. The gene expression profile was evaluated using total RNA sequencing. The proliferation rate was determined colorimetrically. RESULTS: Substantial differences in specific gene groups and pathways were observed between fibroblasts from the two tissues. Significantly enriched gene ontology processes were focused on the extracellular components. Lining mucosa fibroblasts exhibited significantly higher expression of the principal structural collagens, cranial neural crest markers, and homeobox genes associated with positional memory. Masticatory mucosa fibroblasts showed greater expression of genes related to transforming growth factor-ß signalling, which may be associated with fibrosis. In addition, they expressed higher levels of the EP2 prostaglandin E2 receptor and Toll-like receptor 1. Finally, masticatory mucosa fibroblasts exhibited a 10%-30% higher proliferation rate. CONCLUSIONS: Fibroblasts from the lining and masticatory oral mucosae are phenotypically heterogeneous, presenting distinct gene expression profiles and proliferation rates. These features may contribute to their specific physiological functions and have relevance for potential therapeutic applications.
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Fibroblastos , Transcriptoma , Proliferação de Células/genética , Humanos , Mucosa Bucal , Fator de Crescimento Transformador betaRESUMO
OBJECTIVE: Different root modifiers have been proposed in the literature with an attempt to improve the healing process and the success rate of root coverage procedures. The aim of the present retrospective study was to evaluate the effect of three different types of root surface conditioning, namely, tetracycline (TTC), ethylene-di-amino-tetra-acetic acid (EDTA) and saline, on the outcome of root coverage procedures applying the same surgical technique. MATERIALS AND METHODS: Twenty-nine patients with 60 Classes I, II, or III recession defects were treated using connective tissue with a partial-thickness double-pedicle graft. In 21 recession defects root surface was treated with TTC and, in other 21, with EDTA, while in the remaining, saline solution was applied. Statistical analysis consisted of descriptive statistics and Kruskal-Wallis, Mann-Whitney, and chi-square tests. RESULTS: Differences between pre- and postoperative values were statistically significant only within but not between groups. Mean root coverage was 73.25%, 69.19%, and 82.17% in the TTC, the EDTA, and the saline groups, respectively. The study revealed no statistically significant differences for all evaluated parameters between groups. CONCLUSION: Within the limits of this study, root conditioning, prior to root coverage procedures, does not significantly affect their outcome. CLINICAL SIGNIFICANCE: Clinical outcome of root coverage procedures is not related to the type of root surface conditioning.
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Retração Gengival , Tecido Conjuntivo , Gengiva , Retração Gengival/cirurgia , Humanos , Estudos Retrospectivos , Retalhos Cirúrgicos , Raiz Dentária , Resultado do TratamentoRESUMO
AIM: To examine the in vitro biokinetics of hyaluronic acid (HA) from a collagen membrane (CM) and to evaluate the in vivo effect of immersion of the CM in HA solution on its degradation in streptozotocin (STZ)-induced diabetes conditions in a rat calvaria subcutaneous model. BACKGROUND: CM degradation is accelerated in uncontrolled diabetic rats. Immersion of CM in HA has been suggested to decrease their resorption rate without interfering with their tissue integration and structural degradation. However, it is unknown to what extent CM degradation may be influenced by its immersion in HA solution under a condition mimicking a medically compromised situation with an increased inflammatory level such as diabetes. MATERIALS AND METHODS: CMs were soaked in cross-linked HA. Protein adsorption and the HA release were quantified by ELISA. Diabetes was induced in sixteen rats, while 16 healthy rats served as control. CM was prepared and labeled prior to implantation with Biotin. Seventeen CM were immersed in HA and 17 CM in PBS. In each animal, one test or one control disk was implanted. In order to compare the collagen content, two similar non-implanted CM were used as baseline. Fourteen days after surgery, thirty-two animals were sacrificed. The entire calvaria including the skin above, was chemically fixed, decalcified, and embedded in paraffin. Five-µm-thick sections were analyzed histologically and histomorphometrically using H&E and avidin-peroxidase staining. RESULTS: The in vitro results demonstrated that the CM adsorbed roughly 80% of the total HA content. After 10 days, 36.3% of the initial HA remained on the CM. The in vivo results demonstrated that diabetes significantly reduced the thickness of the CM, while HA had a significant effect on keeping the membrane thickness. HA increased the residual collagen content in the diabetic group (P < 0.0001) but no such effect was observed in the healthy group. CONCLUSION: Immersion of CM in HA prior to the implantation delays membrane degradation in uncontrolled diabetic compared with normoglycemic rats.
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Implantes Absorvíveis , Colágeno , Diabetes Mellitus Experimental , Ácido Hialurônico/farmacologia , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Masculino , Ratos , Ratos Wistar , Crânio , SuínosRESUMO
BACGROUND: On June 5th, 2015 at Europerio 8, a group of leading experts were gathered to discuss what has now been 20 years of documented evidence supporting the clinical use of enamel matrix derivative (EMD). Original experiments led by Lars Hammarström demonstrated that enamel matrix proteins could serve as key regenerative proteins capable of promoting periodontal regeneration including new cementum, with functionally oriented inserting new periodontal ligament fibres, and new alveolar bone formation. This pioneering work and vision by Lars Hammarström has paved the way to an enormous amount of publications related to its biological basis and clinical use. Twenty years later, it is clear that all these studies have greatly contributed to our understanding of how biologics can act as mediators for periodontal regeneration and have provided additional clinical means to support tissue regeneration of the periodontium. AIMS: This review article aims to: (1) provide the biological background necessary to understand the rational for the use of EMD for periodontal regeneration, (2) present animal and human histological evidence of periodontal regeneration following EMD application, (3) provide clinically relevant indications for the use of EMD and (4) discuss future avenues of research including key early findings leading to the development of Osteogain, a new carrier system for EMD specifically developed with better protein adsorption to bone grafting materials.
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Cemento Dentário , Perda do Osso Alveolar , Animais , Proteínas do Esmalte Dentário , Regeneração Tecidual Guiada Periodontal , Humanos , Ligamento Periodontal , CicatrizaçãoRESUMO
OBJECTIVES: Increased collagenolytic activity in diabetes may compromise collagen membrane (CM) survival. Tetracycline (TTC) possesses anti-collagenolytic properties and delays CM degradation. This study evaluated macrophage and capillary infiltration within CMs in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in 20 Wistar rats by streptozotocin and 20 served as controls. Biotin-labeled CM discs were immersed in either TTC (50 mg/ml) or PBS. In each animal, 2 discs (TTC and control) were implanted under the parietal periosteum and rats were sacrificed at 2 or 4 weeks post-implantation. The area and thickness of the residual disc collagen were measured following staining with streptavidin, and the number of macrophages and blood vessels within the membranes was determined using specific antibodies (to CD68 and transglutaminase II, respectively). RESULTS: Diabetes significantly reduced the area and thickness of the CMs, while TTC increased CM thickness significantly in both groups of rats at 2 and 4 weeks. Diabetes increased the number of macrophages (â¼eightfold at 2 weeks and â¼fourfold at 4 weeks), but TTC had no significant effect. Finally, diabetes increased the number of blood vessels within the discs (â¼threefold at 2 weeks and â¼twofold at 4 weeks), while TTC had no effect. CONCLUSIONS: Diabetes increases degradation of native CMs and the number of blood vessels and macrophages within them. TTC immersion delays CM degradation without an apparent effect on macrophage and blood vessel penetration. CLINICAL RELEVANCE: Enhanced CM degradation in diabetic conditions which impair guided regenerative procedure outcome is apparently related to increased blood vessel formation and macrophage infiltration.
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Antibacterianos/farmacologia , Colágeno/metabolismo , Macrófagos/metabolismo , Membranas Artificiais , Crânio/cirurgia , Tetraciclina/farmacologia , Animais , Diabetes Mellitus Experimental , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVES: The present study evaluated the degradation of collagen matrix (CM) immersed in tetracycline (TTC) or phosphate-buffered saline (PBS) in diabetic and normoglycemic rats. MATERIALS AND METHODS: Diabetes was induced in 15 rats by systemic streptozotocin (STZ) (experimental); 15 healthy rats served as controls. One day before implantation 60 CM disks, 5 mm in diameter, were labeled with biotin: 30 were immersed in tetracycline (TTC) and 30 in PBS. One disk of each type was implanted subdermally in each rat. Animals were euthanized after 3 weeks, and tissue specimens containing the disks were prepared for histologic analysis. Horseradish peroxidase (HRP)-conjugated streptavidin was used to detect the remaining biotinylated collagen. Residual collagen area within the CM disks was analyzed and compared to baseline. RESULTS: Diabetes significantly increased the CM degradation. Immersion of the CM disks in a 50-mg/mL TTC solution before implantation decreased its degradation both in diabetic and normoglycemic rats. CONCLUSIONS: Diabetes significantly increases collagen matrix degradation; immersion of collagen matrix in TTC before implantation decreases its degradation in both diabetic and normoglycemic conditions. CLINICAL RELEVANCE: Immersion of medical collagen devices in TTC may be an effective means to decrease their resorption rate and increase their effectiveness, especially in situations with increased degradation such as diabetes.
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Antibacterianos/farmacologia , Colágeno/efeitos dos fármacos , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Tetraciclina/farmacologia , Animais , Antibacterianos/administração & dosagem , Masculino , Ratos , Ratos Wistar , Suínos , Tetraciclina/administração & dosagemRESUMO
Periodontal wound healing and regeneration are highly complex processes, involving cells, matrices, molecules and genes that must be properly choreographed and orchestrated. As we attempt to understand and influence these clinical entities, we need experimental models to mimic the various aspects of human wound healing and regeneration. In vivo animal models that simulate clinical situations of humans can be costly and cumbersome. In vitro models have been devised to dissect wound healing/regeneration processes into discrete, analyzable steps. For soft tissue (e.g. gingival) healing, in vitro models range from simple culture of cells grown in monolayers and exposed to biological modulators or physical effectors and materials, to models in which cells are 'injured' by scraping and subsequently the 'wound' is filled with new or migrating cells, to three-dimensional models of epithelial-mesenchymal recombination or tissue explants. The cells employed are gingival keratinocytes, fibroblasts or endothelial cells, and their proliferation, migration, attachment, differentiation, survival, gene expression, matrix production or capillary formation are measured. Studies of periodontal regeneration also include periodontal ligament fibroblasts or progenitors, osteoblasts or osteoprogenitors, and cementoblasts. Regeneration models measure cellular proliferation, attachment and migration, as well as gene expression, transfer and differentiation into a mineralizing phenotype and biomineralization. Only by integrating data from models on all levels (i.e. a single cell to the whole organism) can various critical aspects of periodontal wound healing/regeneration be fully evaluated.
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Gengiva/fisiologia , Modelos Biológicos , Cicatrização , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Regulação da Expressão Gênica , Gengiva/citologia , Gengiva/lesões , Humanos , Técnicas In Vitro , RegeneraçãoRESUMO
AIM: This study evaluated the effects of a topical herbal patch (PerioPatch®) for gingival wound healing in a rat model. MATERIALS AND METHODS: A mid-crestal incision was performed on each side of the edentulous anterior maxilla in 48, 6-month-old, Wistar rats. Full-thickness flaps were raised, repositioned and sutured. Four experimental groups were established: herbal patch, placebo patch, no patch and no patch and no surgery. Patches were placed immediately after surgery and replaced every 12 h for the following 3 days. Half of the animals were killed after 5 and the remaining ones after 12 days. Tissue blocks were retrieved and processed for histological and immunohistochemical evaluation. Epithelial gap, collagen contents, amount of macrophages, cellular proliferation and vascular contents were evaluated in the central incision area. Statistical analysis consisted of two-way anova. RESULTS: The herbal patch group presented the smallest epithelial gap at 12 days, the highest collagen content both at 5 and 12 days, a larger number of proliferating cells at day 5 and more numerous blood vessels at day 12. Macrophage number was similar in all groups. CONCLUSION: Herbal patch improved wound healing in this animal model.
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Gengiva/cirurgia , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Animais , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Centella , Colágeno/análise , Avaliação Pré-Clínica de Medicamentos , Echinacea , Epitélio/efeitos dos fármacos , Epitélio/patologia , Gengiva/efeitos dos fármacos , Gengiva/patologia , Arcada Edêntula/cirurgia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Maxila/cirurgia , Microvasos/efeitos dos fármacos , Microvasos/patologia , Modelos Animais , Placebos , Ratos , Ratos Wistar , Reepitelização/efeitos dos fármacos , Sambucus nigra , Retalhos Cirúrgicos/patologia , Retalhos Cirúrgicos/cirurgia , Fatores de Tempo , Triterpenos/uso terapêutico , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVES: This study evaluated the effect of implant macrodesign and position, related to the bone crest, on bone-to-implant contact (BIC) and crestal bone (CB) in immediate implants. MATERIAL AND METHODS: The study comprised of six foxhound dogs in which 48 immediate implants were placed. Three types of implants from the same manufacturer with similar surface characteristics but different macrodesigns were randomly placed: Group A (external hex with no collar microthreads), Group B (internal hex and collar microrings), and Group C (internal conical connection and collar microrings). Half of the implants were placed leveled with the bone crest (control) and the remaining, 2 mm subcrestally (test). Block sections were obtained after 12 weeks and processed for mineralized ground sectioning. Statistical analysis consisted of nonparametric Friedman and Wilcoxon test. RESULTS: All implants were clinically stable and histologically osseointegrated. Mean BIC percentage within the control group was as follows: A: 42.52 ± 8.67, B: 35.19 ± 18.12, and C: 47.46 ± 11.50. Within the test group: A: 47.33 ± 5.23, B: 48.38 ± 11.63, and C: 54.88 ± 11.73. Differences between each subgroup in the test and the control groups were statistically significant. BIC was statistically significantly higher in the test (50.588 ± 8.663) than in the control (43.317 ± 9.851) group. Within both groups, differences between group C and the other 2 were statistically significant. Distance from the implant shoulder to the buccal CB was statistically significantly larger in the control than in the test group and between subgroups B and C in the control and test groups. Within the test groups, relative bone gain was noticed. CONCLUSIONS: Subcrestal immediate implant positioning may lead to a relatively reduced CB resorption and increased BIC. Implants macrodesign with crestal microrings may enhance BIC in post-extraction implants.
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Remodelação Óssea , Implantes Experimentais , Alvéolo Dental , Animais , Implantação Dentária Endóssea , Planejamento de Prótese Dentária , Cães , Mandíbula/cirurgia , Teste de Materiais , Modelos Animais , Distribuição Aleatória , Extração Dentária , Alvéolo Dental/fisiologiaRESUMO
OBJECTIVES: The objectives of this study were to propose a classification for the bone defects resulting after extraction of a vertically fractured tooth and to review the existing literature about the treatment of such kind of defects by means of dental implants in combination with regenerative procedures. MATERIALS AND METHODS: An electronic search was performed on biomedical databases using a combination of appropriated search terms combined through the use of Boolean operators. All articles concerning the treatment of peri-implant bone dehiscences and fenestrations through guided bone regeneration (GBR) with at least 6 months follow-up were eligible. Outcomes data extracted from the selected articles were summarized using descriptive tables. A classification of the bone defects associated with vertical root fracture (VRF) was also proposed. RESULTS: A total of 33 articles were included in the review. Twenty-three articles (814 implants) were about bone dehiscence treatment, ten articles presented the treatment of fenestrations, and ten (429 implants) adopted vertical bone augmentation. The percentage of bone filling was variable among different procedures and defect classification. The use of resorbable membrane was associated with better outcomes than the use of non-resorbable ones. CONCLUSIONS: Guided bone regeneration for the management of bone defects in the presence of a VRF of the extracted tooth is a viable treatment option. The assessment of bone defect geometry prior to a tooth extraction could be clinically relevant for evaluating the feasibility and the success of immediate implant placement as well as the need of GBR.
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Perda do Osso Alveolar/classificação , Perda do Osso Alveolar/cirurgia , Aumento do Rebordo Alveolar/métodos , Implantação Dentária/métodos , Implantes Dentários , Deiscência da Ferida Operatória/cirurgia , Fraturas dos Dentes/cirurgia , Perda do Osso Alveolar/etiologia , Regeneração Óssea , Humanos , Deiscência da Ferida Operatória/etiologia , Extração DentáriaRESUMO
BACKGROUND: Periodontal disease is caused by subgingival bacteria that adversely affect the host immune system and create and maintain unmitigated inflammation in gingival and periodontal tissues. The condition is also linked to systemic conditions including cardiovascular disease, diabetes, and arthritis. Periodontitis elevates the bacterial load and spreads systemic inflammation through infection and inflammation. The main radiographic sign of periodontitis is marginal bone loss. Risk factors, including medications, smoking, age, and gender, are known to influence periodontal health. However, there is little information about the impact of systemic conditions, and medications on tooth wear. AIM: To assess the association between systemic conditions and medications and radiographic signs of tooth wear (TW) and marginal bone loss (MBL) . MATERIALS AND METHODS: This retrospective analysis was conducted on a group of 2223 consecutive patients who came for dental treatment in the clinics of a large HMO in Israel. Data available for the study included details of concomitant systemic diseases and medication and full-mouth radiographic surveys. Odds ratio and logistic regression analysis were used to detect associations between systemic conditions and medication, and MBL and TW . RESULTS: The results indicated an elevated odds ratio for TW associated with age, gender, and smoking across all age groups. Among young patients, those using proton pump inhibitors and psychiatric medications had an elevated risk of TW. Age, smoking, and diabetes conditions were associated with an increased odds ratio for MBL in all age groups. Psychiatric medications and gender elevated the odds ratio for MBL only among older patients. CONCLUSION: Our results highlight the significant impact of age, gender, and smoking on tooth wear and extend these risks to alveolar bone loss when combined with diabetes and psychiatric conditions.
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OBJECTIVES: Work in animal models has implicated excessive occlusal forces and occlusal trauma as co-destructive factors for periodontitis. The main aim of the present study was to make a radiographic assessment of the effects of excessive occlusal forces, ie occlusal/incisal tooth wear, widening of the periodontal space, and the presence of a mandibular torus, on interproximal marginal bone loss in a large series of patients. A secondary aim was to evaluate the statistical correlation between the parameters in two specific teeth and those of 12 teeth for marginal bone loss and six teeth for occlusal/incisal tooth wear within the same individual. METHOD AND MATERIALS: A total of 1,950 full-mouth radiographic surveys were analyzed retrospectively. Interproximal marginal bone loss was quantified relative to the root length (Schei ruler technique). In addition, occlusal/incisal tooth wear and periodontal ligament space widening of the periodontal space were assessed, as well as the presence of a mandibular torus. Odds ratio and logistic regression analysis were used to determine the association between occlusal trauma and marginal bone loss. RESULTS: The correlation of the measured parameters between the values for specific teeth and the whole dentition was evaluated from data from the first 400 radiographs. Teeth 41 and 33 showed the best correlation to the whole dentition: 0.85 for interproximal marginal bone loss, 0.83 for widening of the periodontal space, and 0.97 for occlusal/incisal tooth wear. The results of a logistic regression analysis with age as an independent variable, revealed a significant association between bone loss and both tooth wear (odds ratio = 2.767) and bone loss and widening of the periodontal space (odds ratio = 2.585). CONCLUSION: Tooth wear was positively correlated to both widening of the periodontal space and marginal bone loss. No correlation was found between the presence of a mandibular torus and marginal bone loss.
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Oclusão Dentária Traumática , Periodontite , Desgaste dos Dentes , Animais , Força de Mordida , Estudos Retrospectivos , Oclusão Dentária Traumática/complicações , Oclusão Dentária Traumática/diagnósticoRESUMO
Uncontrolled diabetes is characterized by aberrant inflammatory reactions and increased collagenolysis. We have reported that it accelerates the degradation of implanted collagen membranes (CM), thus compromising their function in regenerative procedures. In recent years, a group of physiological anti-inflammatory agents called specialized pro-resolving lipid mediators (SPMs) have been tested as a treatment for various inflammatory conditions, either systemically or locally, via medical devices. Yet, no study has tested their effect on the fate of the biodegradable material itself. Here, we measured the in vitro release over time of 100 or 800 ng resolvin D1 (RvD1) incorporated into CM discs. In vivo, diabetes was induced in rats with streptozotocin, while buffer-injected (normoglycemic) rats served as controls. Resolvins (100 or 800 ng of RvD1 or RvE1) were added to biotin-labeled CM discs, which were implanted sub-periosteally over the calvaria of rats. Membrane thickness, density, and uniformity were determined by quantitative histology after 3 weeks. In vitro, significant amounts of RvD1 were released over 1-8 days, depending on the amount loaded. In vivo, CMs from diabetic animals were thinner, more porous, and more variable in thickness and density. The addition of RvD1 or RvE1 improved their regularity, increased their density, and reduced their invasion by the host tissue significantly. We conclude that addition of resolvins to biodegradable medical devices can protect them from excessive degradation in systemic conditions characterized by high degree of collagenolysis.
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Diabetes is a global epidemic accompanied by impaired wound healing and increased risk of persistent infections and resistance to standard treatments. Therefore, there is an immense need to develop novel methods to specifically target therapeutics to affected tissues and improve treatment efficacy. This study aims to use enzyme-responsive nanoparticles for the targeted delivery of an anti-inflammatory drug, dexamethasone, to treat inflammation in diabetes. These nanoparticles are assembled from fluorescently-labeled, dexamethasone-loaded peptide-polymer amphiphiles. The nanoparticles are injected in vivo, adjacent to labeled collagen membranes sub-periosteally implanted on the calvaria of diabetic rats. Following their implantation, collagen membrane resorption is linked to inflammation, especially in hyperglycemic individuals. The nanoparticles show strong and prolonged accumulation in inflamed tissue after undergoing a morphological switch into microscale aggregates. Significantly higher remaining collagen membrane area and less inflammatory cell infiltration are observed in responsive nanoparticles-treated rats, compared to control groups injected with free dexamethasone and non-responsive nanoparticles. These factors indicate improved therapeutic efficacy in inflammation reduction. These results demonstrate the potential use of enzyme-responsive nanoparticles as targeted delivery vehicles for the treatment of diabetic and other inflammatory wounds.
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Diabetes Mellitus Experimental , Nanopartículas , Ratos , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Inflamação/tratamento farmacológico , Colágeno , Dexametasona/farmacologia , Dexametasona/uso terapêuticoRESUMO
Various free connective tissue graft (CTG) harvesting techniques have been reported. The lining epithelium of the palatal graft may be retrieved either intra- or extraorally. This report presents a series of root coverage cases where deepithelialization was intraorally performed before harvesting the graft with a round diamond bur mounted on a low-speed handpiece. Ten single-tooth gingival recession defects in five patients were treated, applying a surgical procedure based on a coronally advanced flap combined with a free CTG that was deepithelialized in situ by the same method. Recession and probing depths and keratinized tissue and recession widths were recorded at baseline and the follow-up evaluations. Follow-up was between 7 and 21 months (mean: 12.1 ± 5.04 months). Clinical, esthetic, and histologic evaluations were performed. Mean root coverage was 89% ± 24.86% (range: 25% to 100%), and complete root coverage was observed in 80% of cases; the esthetic score range was 6 to 9 (mean: 7.44 ± 1.01). Epithelial remnants, although different in proportions, were evident in all samples (range of prevalence: 4.57% to 29.12%). Within the limitations of the small number of clinical cases, the presented in situ deepithelialization technique for CTG seems to be valuable and may accordingly be routinely applied.
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Gengiva , Retração Gengival , Tecido Conjuntivo , Seguimentos , Retração Gengival/cirurgia , Humanos , Raiz Dentária , Resultado do TratamentoRESUMO
Background: Dietary habits, food intake and oral health are important factors for general health. The aim of these present study was to assess the association between implant-supported fixed oral rehabilitation and glycemia, by monitoring HbA1c values before and after implant-supported prostheses (ISP) delivery to diabetic individuals. Methods: Retrospective, cohort study based on dental records. All treatments were performed by experienced oral and maxillofacial surgeons and experienced prosthodontists. Inclusion criteria: ISP delivery, diagnosis of diabetes in the medical files, consecutive individuals. Variables includedprimary outcomedifferences (delta) in HbA1c values prior to implant placement and one year after ISP delivery, early implant failure (EIF). Confounding factors included age, gender, physical status, smoking, implant jaw location, implant length, implant width, total implant count per individual. Results: Statistically significant (p < 0.01) decrease in HbA1c from 7.10 ± 1.09% to 6.66 ± 1.02% following ISP delivery was recorded. The mean HbA1c delta was 0.44 ± 0.73%, where 39.0% of the patients had a significant improvement (delta decrease > 0.5%). Univariate and multivariate model using logistic regression at individual level showed that initial high HbA1c levels was the only factor positively predicting improvement (OR = 1.96, CI [1.22, 3.14], p < 0.01). Univariate model at implant level demonstrated that implants placed in the anterior maxilla also contributed to significant improvement in HbA1c values. Multivariate analysis at implant level was similar to individual level. Number of missing teeth did not affect the results significantly. Conclusion: ISP delivery to partially or completely edentulous diabetic individuals may improve HbA1c balance. The mechanism awaits future elucidation.
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Arcada Edêntula , Estudos de Coortes , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Seguimentos , Hemoglobinas Glicadas , Controle Glicêmico , Humanos , Arcada Edêntula/reabilitação , Arcada Edêntula/cirurgia , Próteses e Implantes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: This study compared dental, periodontal, oral, and joint/muscle tenderness among Israeli combat-induced post-traumatic stress disorder (Ci-PTSD) war veterans to non-PTSD patients. Study design: This retrospective three-arm study compared oral and facial manifestations between 100 Israeli veterans with Ci- PTSD (study group) and 103 non-PTSD periodontal patients (Control group). The study group was further divided into two subgroups of individuals who received psychiatric medications (40 patients) or did not (60 patients). All patients underwent complete dental, oral, and periodontal examinations, including assessing signs of parafunction. Results: All PTSD patients had poor oral hygiene. The plaque index (PI) was higher in the PTSD group compared to the control group (0.72 ± 0.28 vs. 0.45 ± 0.29, respectively, p < 0.001). The decayed, missing, and filled teeth score (DMFt) was higher in the PTSD population than in the controls (19.97 ± 8.07 vs. 13.05 ± 6.23 p < 0.05). Severe periodontal disease was more common among the PTSD subgroup taking medications (med -group) (62.5%) compared to the nonmedicated group (non-med group) (30.0%) and the controls (27.2%) (p = 0.001). Heavy smoking was more prevalent in the medicated PTSD patients than in other groups. Conclusions: The present study shows higher morbidities in combat-induced PTSD patients, including oral, dental, and periodontal manifestations, especially in medicated patients.
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The aim of the present study was to generate an international and multidisciplinary consensus on the clinical management of implant protrusion into the maxillary sinuses and nasal fossae. A total of 31 experts participated, 23 of whom were experts in implantology (periodontologists, maxillofacial surgeons and implantologists), 6 were otolaryngologists and 2 were radiologists. All the participants were informed of the current scientific knowledge on the topic based on a systematic search of the literature. A list of statements was created and divided into three surveys: one for all participants, one for implant providers and radiologists and one for otolaryngologists and radiologists. A consensus was reached on 15 out of 17 statements. According to the participants, osseointegrated implants protruding radiographically into the maxillary sinus or nasal fossae require as much monitoring and maintenance as implants fully covered by bone. In the event of symptoms of sinusitis, collaboration between implant providers and otolaryngologists is required. Implant removal should be considered only after pharmacological and surgical management of sinusitis have failed.