Peri-implantitis with a potential axis to brain inflammation: an inferential review.

Peri-implantitis (PI) is a chronic, inflammatory, and infectious disease which affects dental implants and has certain similarities to periodontitis (PD). Evidence has shown that PD may be related to several types of systemic disorders, such as diabetes and insulin resistance, cardiovascular diseases, respiratory tract infections, adverse pregnancy outcomes, and neurological disorders. Furthermore, some types of bacteria in PD can also be found in PI, leading to certain similarities in the immunoinflammatory responses in the host. This review aims to discuss the possible connection between PI and neuroinflammation, using information based on studies about periodontal disorders, a topic whose connection with systemic alterations has been gaining the interest of the scientific community. Literature concerning PI, PD, and systemic disorders, such as neuroinflammation, brain inflammation, and neurological disorder, was searched in the PubMed database using different keyword combinations. All studies found were included in this narrative review. No filters were used. Eligible studies were analyzed and reviewed carefully. This study found similarities between PI and PD development, maintenance, and in the bacterial agents located around the teeth (periodontitis) or dental implants (peri-implantitis). Through the cardiovascular system, these pathologies may also affect blood-brain barrier permeability. Furthermore, scientific evidence has suggested that microorganisms from PI (as in PD) can be recognized by trigeminal fiber endings and start inflammatory responses into the trigeminal ganglion. In addition, bacteria can traverse from the mouth to the brain through the lymphatic system. Consequently, the immune system increases inflammatory mediators in the brain, affecting the homeostasis of the nervous tissue and vice-versa. Based on the interrelation of microbiological, inflammatory, and immunological findings between PD and PI, it is possible to infer that immunoinflammatory changes observed in PD can imply systemic changes in PI. This, as discussed, could lead to the development or intensification of neuroinflammatory changes, contributing to neurodegenerative diseases.

The Resolution of Periodontal Inflammation Promotes Changes in Cytokine Expression in the Intestine and Gingival Tissues of Aged Rats with DSS-Induced Colitis.

Our research aimed to explore how resolving periodontal inflammation impacts cytokine expression in the colons of aged Wistar rats. Research studies involving animals have been conducted to investigate the two-way relationship between periodontitis and inflammatory bowel disease (IBD), where chronic inflammation in either the mouth or intestines can negatively affect the other. We allocated seventeen male Wistar rats aged between 8 and 11 months to one of four groups: (1) ligature-induced periodontitis (LIP) without the resolution of periodontal inflammation (RPI) (LIP; n = 4), (2) LIP + RPI (n = 4), (3) LIP + dextran-sulphate-sodium-induced colitis (DIC) without RPI (n = 4), and LIP + DIC + RPI (n = 5). We performed histopathological and immunological analyses on periodontal and intestinal tissues and analysed cytokine expressions using a Rat Cytokine 23-Plex Immunoassay. Our findings showed that animals with and without DIC who underwent RPI showed significantly lower levels of IL-2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-18, and TNF-α in the intestine compared to those without treatment. The RPI effectively reduced the number of inflammatory cells in the lamina propria and restored the epithelial barrier in the intestine in animals with DIC. The resolution of periodontal inflammation significantly reduced the levels of pro-inflammatory cytokines and chemokines in the intestines of aged rats with and without DSS-induced colitis.

Avaliação do comportamento das fibras colágenas periodontais durante a progressão da periodontite experimental em ratos / Evaluation of the behaviour of periodontal collagen fibers during the progression of experimental periodontitis in rats

Introdução: A periodontite é uma doença infecto-inflamatória, resultante da disbiose microbiana e da resposta do hospedeiro, que leva à destruição dos tecidos de suporte dentário, inclusive das fibras colágenas periodontais, podendo culminar na perda do elemento dental. Objetivo: Avaliar o comportamento das fibras colágenas periodontais durante a progressão da periodontite experimental induzida em ratos. Material e método: Doze ratos Wistar foram distribuídos nos grupos: Controle (C), Periodontite Experimental 14-dias (PE-14d), Periodontite Experimental 21-dias (PE-21d) e Periodontite Experimental 42-dias (PE-42d). No dia 0, os animais do grupo C foram eutanasiados. Neste mesmo dia, os animais remanescentes foram submetidos à instalação de uma ligadura de algodão ao redor do primeiro molar inferior esquerdo para indução da periodontite experimental. Tais animais foram eutanasiados aos 14 (PE-14d), 21 (PE-21d) e 42 (PE-42d) dias após a instalação da ligadura. Executou-se o processamento histológico das hemimandíbulas e as secções foram submetidas à reação histoquímica pelo vermelho picro-sirius. A análise qualitativa descritiva foi realizada sob microscopia de luz polarizada, na região de furca dental, evidenciando as fibras do ligamento periodontal. Resultado: O grupo C exibiu feixes espessos e orientados de fibras colágenas maduras, condizentes com aspecto de normalidade. Os grupos com periodontite experimental exibiram desestruturação tecidual severa, com fibras colágenas imaturas e de menor espessura, sendo tais condições mais exacerbadas nos grupos PE-14d e PE-21d. Conclusão: As fases iniciais da periodontite apresentam caráter agudo e, portanto, resultam na rápida destruição dos tecidos periodontais de suporte, prejudicando potencialmente a fibrilogênese e a reestruturação do colágeno no ligamento periodontal.

Introduction: Periodontitis is an infectious-inflammatory disease resulting from microbial dysbiosis and host response that leads to the destruction of tooth support tissues, including periodontal collagen fibers, which may culminate in tooth loss. Objective: To evaluate the behavior of periodontal collagen fibers during the progression of induced experimental periodontitis in rats. Material and method: Twelve Wistar rats were distributed into groups: Control (C), 14-days Experimental Periodontitis (PE-14d), 21-days Experimental Periodontitis (PE-21d) and 42-days Experimental Periodontitis (PE-42d). At day 0, the animals of group C were euthanized. At the same day, the remaining animals were submitted to the installation of a cotton ligature around the lower left first molar for the induction of experimental periodontitis. The animals were euthanized at 14 (PE-14d), 21 (PE-21d) and 42 (PE-42d) days after the installation of ligature. Histological processing of the hemi-mandibles was performed and the sections underwent histochemical reaction using picro-sirius red. The descriptive qualitative analysis was performed under polarized light microscopy, in the dental furcation region, evidencing the fibers of the periodontal ligament. Result: Group C exhibited thick and oriented bundles of mature collagen fibers, consistent with a normal appearance. The groups with experimental periodontitis exhibited severe tissue disruption, with immature and thinner collagen fibers, with such conditions being more exacerbated in the PE-14d and PE-21d groups. Conclusion: The early stages of periodontitis present acute response, and therefore result in rapid destruction of periodontal support tissues and potentially impair fibrillogenesis and collagen restructuring in the periodontal ligament.

Effectiveness of antimicrobial photodynamic therapy mediated by butyl toluidine blue in preventing medication-related osteonecrosis of the jaws in rats.

BACKGROUND: Medication-related osteonecrosis of the jaws (MRONJ) is difficult to treat, therefore, prevention would be the ideal clinical approach. This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT), mediated by butyl toluidine blue (BuTB) in the prevention of MRONJ-like lesions after tooth extraction in rats. METHODS: Twenty-eight senescent female rats were distributed in groups: VEH and VEH-aPDT, treated with vehicle, ZOL and ZOL-aPDT, treated with 100 µg/Kg of zoledronate, both treatments every three days over seven weeks. After three weeks from the commencement of treatment, the mandibular first molar was extracted. For the VEH and ZOL groups, no local treatment was performed, while with the VEH-aPDT and ZOL-aPDT groups, photodynamic treatment was carried out at 0, 2, and 4 days after extraction. For aPDT, 500µl of BuTB solution was deposited on the dental extraction site (0.5 mg/ml; 60 s), followed by irradiation with low-level laser (InGaAIP; 660 nm; 35 mW; 74.2 J/cm²; 60 s). After 28 postoperative days, euthanasia was performed. The hemimandibles were processed to: (1) histological analysis of tissue repair; (2) histometric analysis of the percentage of newly formed bone tissue (PNFBT) and percentage of non-vital bone tissue (PNVBT); (3) immunohistochemical analysis for tartrate-resistant acid phosphatase (TRAP). RESULTS: The ZOL and ZOL-aPDT groups showed less TRAP-positive cells when compared with VEH and VEH-aPDT. The ZOL group demonstrated great compromise in the tissue repair process, consistent with MRONJ-like lesions. VEH, VEH-aPDT and ZOL-aPDT presented a favorable tissue repair process. PNFBT in the ZOL group was lower than in the VEH, VEH-aPDT and ZOL-aPDT groups, whereas PNVBT in the ZOL group was higher than in the VEH, VEH-aPDT and ZOL-aPDT groups. CONCLUSION: aPDT mediated by BuTB prevented the occurrence of MRONJ-like lesions after tooth extraction in rats.

In vivo comparative study of the effects of using the enamel matrix derivative and/or photobiomodulation on the repair of bone defects.

BACKGROUND: The repair of bone defects has been the subject of many studies that have shown inconclusive results as to what is the best bone substitute. MATERIAL AND METHODS: Bone defects (Ø 2 mm) were induced on the tibia of seventy-two rats, which were distributed into the following four groups/treatments (n=18 each): Control: no treatment; EMD: enamel matrix derived protein; PBM: photobiomodulation therapy (660 nm, 0,035 W, 60 s); EMD + PBM: EMD and immediate treatment with PBM (660 nm, 0,035 W, 60 s). Six animals from each group were euthanized after 10, 30 and 60 days. Histological and immunohistochemistry analyses (osteocalcin - OCN and tartrate-resistant acid phosphatase - TRAP) were performed with scores for each of the biological events. RESULTS: All performed treatments resulted in an increased filling and maturation of bone tissue, being greater in the EMD and EMD + PBM groups in the 30 day period, compared to the Control group. The immunostaining of OCN was greater at 60 days in all treated groups than in the Control over the same period. TRAP immunostaining was higher at 30 days in all treated groups, and lower in groups EMD and PBM after 60 days, compared to the Control over the same period. There was greater immunostaining in the EMD + PBM group after 10 days than in the Control and EMD groups in the same period. CONCLUSIONS: These results lead to the conclusion that treatments with EMD and PBM, both separate and in association were effective in filling and maturing bone tissue in tibial bone cavities, with greater effectiveness in the period of 30 days in the EMD and EMD + PBM groups. Key words:Enamel matrix proteins, low-level laser, bone, animal research.

Adjuvant effects of curcumin as a photoantimicrobial or irrigant in the non-surgical treatment of periodontitis: Systematic review and meta-analysis.

AIM: Curcumin (CUR) has been used clinically in several studies as a subgingival irrigant or as a photoantimicrobial in combination with a blue light-emitting diode (LED) in antimicrobial photodynamic therapy (aPDT) adjuvant to scaling and root planing (SRP). The aim of this study was to assess the effectiveness of CUR as an irrigant or as a photoantimicrobial in conjunction with the blue LED in aPDT adjuvant to SRP, compared to SRP as conventional mechanical treatment. MATERIALS AND METHODS: Fifteen randomized controlled trials (RCT) were included in a qualitative analysis after researching the databases: PubMed / MEDLINE, SCOPUS, EMBASE, Cochrane Central, Web of Science and Scielo. Manual searches were also performed. Five studies were submitted to quantitative analysis, evaluating periodontal clinical parameters such as probing depth (PD) and clinical attachment level (CAL). RESULTS: The obtained results have shown clinical benefits in PD reduction and CAL gains at 3 months with the use of CUR as adjuvant therapy to SRP, both as an irrigant or photoantimicrobial, in comparison with SRP monotherapy. CONCLUSION: Currently, there is evidence that treatment with CUR applied as irrigant or in conjunction with the blue LED as aPDT presents superior clinical results in the short term, for clinical periodontics parameters like as PD reduction and CAL gain, when compared to SRP monotherapy in the non-surgical treatment of periodontitis. However, these results cannot be proven in the long term.

Miniplates coated by plasma electrolytic oxidation improve bone healing of simulated femoral fractures on low bone mineral density rats.

The treatment of polytrauma patients represents a great challenge in the maxillofacial and orthopedic surgery fields. Therefore, this study tested the hypothesis that the use of a bioactive coating (by plasma electrolytic oxidation, PEO) on titanium microplates could improve the fracture healing of low bone mineral density (BMD) rats. Thirty female rats underwent bilateral ovariectomy surgery (OVX), and 35 rats underwent fake surgery (SHAM). Three months later, animals were subjected to femoral fracture simulation and were fixed with either non-coated (CONV) or coated (PEO) titanium miniplates. Eight weeks postoperatively, microplate/bone complexes were analyzed through computed microtomography, histometric, confocal microscopy, molecular, and biomechanical analysis. Bioactive elements (Ca and P) were incorporated on the PEO microplate and the surface was modified in a volcano-like structure. In the microCT analysis the OVX/PEO group had greater values for Tb.Th (bone trabecular thickness), Tb.Sp (separation of bone trabeculae) and Tb.N (number of trabeculae) parameters compared to the OVX/CONV group. According to histometric analysis, the OVX/PEO group showed significantly higher new bone formation than the OVX/CONV group (P < 0.05). For the fluorochrome area, the OVX groups (PEO and CONV) showed greater values for calcein precipitation (old bone) than alizarin red (new bone). Molecular results showed greater values for proteins related to the final phase of bone formation (P < 0.05) in the OVX/PEO group. The OVX/PEO group showed higher bone/miniplate system resilience compared to the others (P < 0.05). It was concluded that PEO coating optimizes bone healing on simulated femoral fractures in low bone mineral density rats. This sheds new light in the treatment of osteoporotic patients with bone fractures.

Antimicrobial photodynamic therapy compared to systemic antibiotic therapy in non-surgical treatment of periodontitis: Systematic review and meta-analysis.

BACKGROUND: Periodontitis is one of the most prevalent inflammatory diseases in humans. It is associated with the presence of bacteria and is mediated by the host's immune response This study represents a systematic review and meta-analysis trying to answer the following question: "What is the effect of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) compared to systemic antibiotic therapy with amoxicillin plus metronidazole (AMX+MTZ) on the non-surgical treatment of periodontitis?". METHODS: Clinical studies comparing aPDT with systemic use of AMX+MTZ were searched until January of 2020 using the databases: PubMed, MEDLINE, SCOPUS, EMBASE, Cochrane Central, Web of Science and Scielo, as well manual searches in related journals. Periodontal clinical parameters such as probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were statistically analyzed. RESULTS: Five randomized clinical studies (RCTs) were included within the eligibility criteria, and served as a basis for qualitative and quantitative analyzes. All the studies reported an improvement in the clinical parameters with both therapies, although in a direct comparison, our analyzes did not find statistical differences that indicate the superiority of one supporting treatment in relation to the other. CONCLUSION: Although the limited number of RCTs and the great heterogeneity between them, it can be concluded that aPDT presents similar clinical results compared to antibiotic therapy with AMX+MTZ as adjuvants in the non-surgical treatment of periodontitis.

The Effectiveness of the Low-Level Laser, Antibiotic and Surgical Therapy in the Treatment of Medication-Related Osteonecrosis of the Jaws: A Case Report.

Introduction: Bisphosphonates consist of a range of drugs used in the treatment of osteopathy or some osteotropic malignancies. Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse consequence of their use. Conventional treatment is not always effective, so it is necessary to resort to the use of adjuvant therapies. This study aimed to evaluate the effectiveness of the association of surgery, antibiotic therapy and low-level laser (LLL) therapy as a treatment strategy for MRONJ through the presentation of a clinical case. Case Presentation: A 49-year-old female patient presented for the diagnosis and treatment of bone lesions in the maxillae. The patient reported that she had used zoledronate for 1 year. Five years later there were 2 painless bone lesions on both sides of the maxilla, following the extraction of the first upper molars. Clinical, tomographic and histopathologic examination established the diagnosis of MRONJ. The treatment consisted of the curettage of the necrotic bone, antibiotic and thirteen LLL therapy sessions. Integral mucosal healing was observed after a two-month follow-up and no symptoms were detected. The patient was evaluated at 6 and 12 postoperative months without complications. Conclusion: The combination of surgery, antibiotic therapy, and LLL therapy has shown to be effective in the treatment of MRONJ.

Application of Autologous Platelet-Rich Plasma on Tooth Extraction Site Prevents Occurence of Medication-Related Osteonecrosis of the Jaws in Rats.

This study evaluated the effects of local application of autologous platelet-rich plasma (PRP) on the tooth extraction site of rats presenting the main risk factors for medication-related osteonecrosis of the jaw (MRONJ). For seven weeks, senile rats were submitted to systemic treatment with vehicle (VEH and VEH-PRP) or 100 µg/Kg of zoledronate (ZOL and ZOL-PRP) every three days. After three weeks, the first lower molar was extracted. VEH-PRP and ZOL-PRP received PRP at the tooth extraction site. Euthanasia was performed at 28 days postoperatively. Clinical, histopathological, histometric and immunohistochemical analyses were carried out in histological sections from the tooth extraction site. ZOL showed lower percentage of newly formed bone tissue (NFBT), higher percentage of non-vital bone tissue (NVBT), as well as higher immunolabeling for TNFα and IL-1ß. In addition, ZOL presented lower immunolabeling for PCNA, VEGF, BMP2/4, OCN and TRAP. VEH and ZOL-PRP showed improvement in the tooth extraction site wound healing and comparable percentage of NFBT, VEGF, BMP2/4 and OCN. Local application of autologous PRP proved a viable preventive therapy, which is safe and effective to restore tissue repair capacity of the tooth extraction site and prevent the occurrence of MRONJ following tooth extraction.

Antimicrobial photodynamic therapy improves the alveolar repair process and prevents the occurrence of osteonecrosis of the jaws after tooth extraction in senile rats treated with zoledronate.

This study evaluated the effects of antimicrobial photodynamic therapy (aPDT) in the alveolar repair of rats with major risk factors for bisphosphonate-related osteonecrosis of the jaws (BRONJ). Senile rats received 0.45 ml of vehicle (VEH and VEH/aPDT) or 0.45 ml of zoledronate (ZOL and ZOL/aPDT) every three days for seven weeks. After three weeks of treatment, the first lower left molar was extracted. VEH/aPDT and ZOL/aPDT were submitted to aPDT on the extraction site at 0, 2 and 4 days postoperatively. Euthanasia was performed 28 days postoperatively and the extraction site was evaluated by clinical, histological, histometric, histochemical and immunohistochemical analysis. ZOL showed tissue repair impairment; lower percentage of newly formed bone tissue (NFBT); higher percentage of non-vital bone tissue (NVBT); fewer mature collagen fibers and increased immunolabeling for tumor necrosis factor (TNFα), interleukin (IL)-1ß and IL-6. ZOL/aPDT showed clinical and histological characteristics of the extraction site, percentage of NFBT and percentage of mature collagen fiber similar to VEH. Percentage of NVBT and immunolabeling for inflammatory cytokines in ZOL/aPDT was lower than in ZOL. Immunolabeling for tartarato-resistant acid phosphatase (TRAP) was lower in ZOL and ZOL/aPDT. aPDT in the dental extraction site improves tissue repair process and prevents the occurrence of BRONJ-like lesions after tooth extraction.

Photomodulation multiple sessions as a promising preventive therapy for medication-related osteonecrosis of the jaws after tooth extraction in rats.

The aim of this study was to evaluate the effects of photobiomodulation (PBM) with multiple sessions of low-level laser on the alveolar repair process of rats with major risk factors for medication-related osteonecrosis of the jaws (MRONJ). Senile rats received 0.45 mL of vehicle (VEH and VEH-PBM) or 0.45 mL of 100 µg/kg zoledronate (ZOL and ZOL-PBM) administrated intraperitoneally every two days during seven weeks. After three weeks of initiation of drug treatment the first lower left molar was extracted. No local treatment was performed in VEH and ZOL. VEH-PBM and ZOL-PBM were submitted to laser irradiation (660 ±â€¯10 nm; 0.035 W; 2.1 J; 60 s) on the extraction site at 0, 2 and 4 days postoperatively. Euthanasia was performed 28 days after tooth extraction. Histological sections of the hemimandible were submitted to histopathological and histomorphometric analysis, as well as to histochemistry for collagen fiber maturation and immunohistochemistry for pro-inflammatory cytokines. In ZOL, general impairment of tissue repair, areas with osteonecrosis, lower newly formed bone tissue (NFBT), smaller amount of mature collagen fibers and increased immunoreactivity for TNFα, IL-1ß and IL-6 were observed when compared to VEH and VEH-PBM. ZOL-PBM showed significant improvement in some parameters compared to ZOL, such as positive repair tissue, higher NFBT, greater amount of mature collagen fibers, besides TNFα and IL-1ß immunoreactivity decrease. Zoledronate treatment severely compromised the tissue repair process of the tooth extraction site in rats with major risk factors for MRONJ. Based on parameters employed in the present study, PBM in multiple sessions can improve the alveolar repair process, constituting a promising preventive therapy to avoid the onset of post-extraction MRONJ.