Periodontal Tissue Breakdown Research Articles

Clinical and Biochemical Effects of Antioxidant Gel as a Local Drug Delivery Agent in Stage II Grade A Periodontitis Patients: A Prospective Clinical Study.

Background Periodontal tissue breakdown is mainly due to pathogenic bacteria and dysregulated immune response resulting in the production of reactive oxygen species/reactive nitrogen species (ROS/RNS) causing tissue degradation. Scaling and root planing (SRP)isusually donefor the management of periodontitis. However,it has been reported thatadjuncts like antibiotics, antiseptics, and antioxidants in the form of local drug delivery enhance the outcome of SRP. Aim The present clinical study aims toexamine the efficacy of an antioxidant oral gel (Bluem®) as a local drug delivery agent adjunct to SRPin the management of stage II grade A periodontitis in terms of clinical and biochemical parameters. Materials and methods The prospective clinical study was conducted among 40 stage II grade A periodontitis patients. The participants were then divided into two groups: Group 1 (Control)-SRP alone (n=20)and Group 2 (Test)-antioxidant gel (Bluem®) with SRP (n=20). Clinical variables including plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) were recorded. Saliva (unstimulated) specimens were collected to measure total oxidant status (TOS), total antioxidant capacity (TAOC), and oxidative stress index (OSI). Specimen collection and assessment of clinical variables were done before intervention (baseline) and after three months. SPSS Software (Version 20.0, Armonk, NY, USA: IBM Corp) was used for statistical analysis. Intragroup and intergroup comparisons were done by paired t-test and independent t-test, respectively. A p-value <0.05 indicated that the result was statistically significant. Results On intragroup analysis, both the groups at three months revealed statistically significant improvement of PI, GI, PD, CAL, TOS, TAOC, and OSI (p<0.05) from baseline. Intergroup comparison in the third month showed a statistically significant improvement in favor of Group 2 in terms of all the clinical and biochemical parameters (p<0.05) except for PI (p>0.05). Conclusion The locally delivered antioxidant gel as an adjunct to SRP seemsto be effective in reducing oxidative stress and improving the periodontal parameters among stage II grade A periodontitis patients.

The effect of cacao bean extracts on the prevention of periodontal tissue breakdown in diabetic rats with orthodontic tooth movements

ObjectiveProper management of orthodontic treatment in diabetic patients is essential due to the heightened risk of periodontal tissue breakdown associated with hyperglycemia. Cacao bean extracts (CBE) are known to reduce the inflammatory response and increase synthesis and angiogenesis in periodontitis. Therefore, this study aims to examine the effect of CBE on preventing periodontal tissue breakdown in diabetes with orthodontic force. MethodsA total of 25 Wistar rats were divided randomly into 5 groups, including non-diabetes, diabetes, diabetes cacao 125, 250, and 500 mg/kg BW. Diabetic rats were induced with the stratified dose of Streptozotocin, and a 30-g-force from orthodontic device was applied in all groups. Diabetes cacao group was given CBE for 7 days using a gastric probe. GCF samples were used to analyze the eNOS level through the ELISA method. NFκB, Collagen-1, and FGF-2 expression were then assessed using the immunohistochemical method, while the number of fibroblasts and blood vessels was observed using hematoxylin-eosin stained tissue. The data obtained were analyzed with one-way ANOVA and post hoc tests, with p < 0.05. ResultsCBE at a dose of 250 mg/kg BW significantly increased eNOS level, Collagen-1, and FGF-2 expression, and the number of fibroblasts and blood vessels in diabetes groups. Meanwhile, the treatment decreased NFκB expression in diabetes groups (p < 0.05). ConclusionThis study proved that CBE increased periodontal ligament synthesis and angiogenesis and decreased inflammatory response, thereby preventing periodontal tissue breakdown in diabetic rat models with tooth movement.

Comparison of immunoexpression of dendritic cells, mast cells and blood vessels in periodontal disease between adults and elderly.

The aim of this study was to compare, in adults and elderly individuals, the immunoexpression of immature and mature dendritic cells (DCs), mast cells, and blood vessels in healthy and diseased gingival tissues. The expressions of immunohistochemical markers, including CD1a (immature dendritic cells), CD83 (mature dendritic cells), tryptase (mast cells) and CD34 (blood vessels), were analyzed in gingival biopsies from elderly (n = 27) and adult (n = 127) patients presenting health, gingivitis and periodontitis. Positive cells for each specimen and marker were counted. There were no differences in the immunostaining of DCs, mast cells and the amount of blood vessels among gingival biopsies with health, gingivitis and periodontitis in adult and elderly subjects (p > 0.05). Immature DCs were more frequent in tissues with gingivitis and periodontitis in elderly patients, when compared to adults (p < 0.05). Furthermore, degranulated mast cell counts were higher, whereas the number of microvessels was lower in gingivitis in the elderly, when compared to adults (p < 0.05). Diseased periodontal sites in the elderly present an overall significant overexpression of immature DCs and degranulated mast cells, in relation to those of adults. Furthermore, gingivitis in elderly is associated with decreased microvessel growth. These immunoinflammatory differences between elderly and adults may have implications in periodontal tissue breakdown in the late adulthood. Further studies should be performed to elucidate this hypothesis. Understading the relationship between aging and changes in immune cells during periodontal inflammation may lead to therapeutic targets for the future management of periodontal diseases.

Co-occurrence of Periodontitis and Diabetes-Related Complications

Periodontitis is a common finding among people with diabetes mellitus (DM) and has been cited as a DM complication. Whether and how periodontitis relates to other diabetes-related complications has yet to be explored. This study aims to examine the clustering of periodontitis with other diabetes-related complications and explore pathways linking diabetes-related complications with common risk factors. Using data from participants with DM across 3 cycles of the National Health and Nutrition Examination Survey (NHANES) (n = 2,429), we modeled direct and indirect pathways from risk factors to diabetes-related complications, a latent construct comprising periodontitis, cardiovascular diseases, proteinuria, and hypertension. Covariates included age, sex, socioeconomic status (SES), smoking, physical activity, healthy diet, alcohol consumption, hemoglobin A1c (HbA1c), dyslipidemia, and body mass index (BMI). Sensitivity analyses were performed considering participants with overweight/obesity and restricting the sample to individuals without DM. Periodontitis clustered with other diabetes complications, forming a latent construct dubbed diabetes-related complications. In NHANES III, higher HbA1c levels and BMI, older age, healthy diet, and regular physical activity were directly associated with the latent variable diabetes-related complications. In addition, a healthy diet and BMI had a total effect on diabetes-related complications. Although sex, smoking, dyslipidemia, and SES demonstrated no direct effect on diabetes-related complications in NHANES III, a direct effect was observed using NHANES 2011–2014 cycles. Sensitivity analysis considering participants with overweight/obesity and without DM showed consistent results. Periodontal tissue breakdown seems to co-occur with multiple diabetes-related complications and may therefore serve as a valuable screening tool for other well-known diabetes-related complications.

A Local Desiccant Antimicrobial Agent as an Alternative to Adjunctive Antibiotics in the Treatment of Periodontitis: A Narrative Review.

Periodontitis is one of the most common oral polymicrobial infectious diseases induced by the complex interplay between the altered subgingival microbiota and the host's dysregulated immune-inflammatory response, leading to the initiation of progressive and irreversible destruction of the periodontal tissues and eventually to tooth loss. The main goal of cause-related periodontal therapy is to eliminate the dysbiotic subgingival biofilm in order to arrest local inflammation and further periodontal tissue breakdown. Because, in some cases, subgingival mechanical instrumentation has limited efficiency in achieving those goals, various adjunctive therapies, mainly systemic and locally delivered antimicrobials, have been proposed to augment its effectiveness. However, most adjunctive antimicrobials carry side effects; therefore, their administration should be precociously considered. HybenX® (HY) is a commercial therapeutical agent with decontamination properties, which has been studied for its effects in treating various oral pathological conditions, including periodontitis. This review covers the current evidence regarding the treatment outcomes and limitations of conventional periodontal therapies and provides information based on the available experimental and clinical studies related to the HY mechanism of action and effects following its use associated with subgingival instrumentation and other types of dental treatments.

Contribution of -Omics Technologies in the Study of Porphyromonas gingivalis during Periodontitis Pathogenesis: A Minireview.

Periodontitis is a non-communicable chronic inflammatory disease characterized by the progressive and irreversible breakdown of the soft periodontal tissues and resorption of teeth-supporting alveolar bone. The etiology of periodontitis involves dysbiotic shifts in the diversity of microbial communities inhabiting the subgingival crevice, which is dominated by anaerobic Gram-negative bacteria, including Porphyromonas gingivalis. Indeed, P. gingivalis is a keystone pathogen with a repertoire of attributes that allow it to colonize periodontal tissues and influence the metabolism, growth rate, and virulence of other periodontal bacteria. The pathogenic potential of P. gingivalis has been traditionally analyzed using classical biochemical and molecular approaches. However, the arrival of new techniques, such as whole-genome sequencing, metagenomics, metatranscriptomics, proteomics, and metabolomics, allowed the generation of high-throughput data, offering a suitable option for bacterial analysis, allowing a deeper understanding of the pathogenic properties of P. gingivalis and its interaction with the host. In the present review, we revise the use of the different -omics technologies and techniques used to analyze bacteria and discuss their potential in studying the pathogenic potential of P. gingivalis.

A Multidisciplinary Approach for the Management of Iatrogenic Severe Periodontitis Following Orthodontic Treatment with a 12-Year Follow-up.

Orthodontic treatment aims to realign teeth in a functional and esthetic manner. When applied on an unhealthy periodontium, this may lead to advanced periodontal tissue breakdown. The present 12-year follow-up report describes the multidisciplinary management of a severe, iatrogenic, generalized periodontitis case that was caused/aggravated by orthodontic therapy on unhealthy periodontal tissues. Prompt therapy was applied through nonsurgical and surgical approaches, including soft and hard tissue grafting procedures combined with corrective orthodontic treatment on healthy tissues. This report is a clear demonstration that early disease detection and proper diagnosis combined with appropriate therapeutic approaches concomitant with strict supportive periodontal therapy could lead to long-term successful and maintainable outcomes, even in hopeless cases.

The Role of Type-2 Diabetes Mellitus in the Progressivity of Periodontitis Stage IV Grade C: A Case Report

Background: According to the American Academy of Periodontology (AAP)’s classification of periodontal disease in 2017, diabetes mellitus is one of the grade modifiers of the progressivity of the disease, which is determined by the HbA1c level of a patient. Systemic condition is often considered as a risk factor that aggravates periodontal tissue breakdown. However, the progressivity of periodontal disease can also be found in healthy (nondiabetic) patients.&#x0D; Objective: To identify the role of type-2 diabetes mellitus and its effect on the severity of periodontal breakdown in periodontitis stage 4 grade C patients.&#x0D; Case Report: This case report describes the condition of female patients, aged 30–40 years, who presented to the periodontology clinic in RSKGM FKG UI, with the chief complaint of severe tooth mobility. The patients reported were healthy and diabetic (type-2 diabetes mellitus) patients diagnosed with periodontitis stage 4 grade C. Initial therapies were carried out, such as, such as scaling, occlusal adjustment and dental splint.&#x0D; Results: Clinical outcomes after one week showed no inflammation, no oedematous, no redness on gingiva and less mobility on several teeth. Both groups showed extended and aggressive progress of the disease, however, the systemic conditions also played a critical role in the overall periodontal tissue breakdown.&#x0D; Conclusion: Management of systemic disease is crucial in order to prevent periodontal breakdown or complications that could happen in periodontal therapies.&#x0D; Keywords: periodontitis, systemic disease, diabetes mellitus, case report

Gut flora alterations due to lipopolysaccharide derived from Porphyromonas gingivalis.

Gut dysbiosis induces 'leaky gut,' a condition associated with diabetes, NASH, and various auto-immune diseases. Porphyromonas gingivalis is a periodontopathic bacterium which causes periodontal tissue breakdown, and often enters the systemic blood flow. Oral administration of P. gingivalis induced gut dysbiosis in mice model, but no systemic administration of P. gingivalis has been reported thus far. In the present study, we investigated the effect of P. gingivalis-derived lipopolysaccharide (Pg-LPS) on the intestinal flora of our established mouse model. Eight-week-old C57BL/6J mice were intraperitoneally administered Pg-LPS. Three months later, DNA was extracted from stool, and RNA from the small and large intestines. After euthanizing the mice, pathological sections of the intestinal tract were prepared and stained with hematoxylin and eosin (H&E). Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 expression levels were evaluated using quantitative PCR. 16S rRNA gene PCR amplicon analysis data were acquired using NGS. Microbial diversity and composition were analyzed using Quantitative Insights into Microbial Ecology 2. Furthermore, alterations in microbial function were performed by PICRUSt2. No significant inflammatory changes were observed in the H&E. No significant differences in the mRNA levels of IL-1β, IL-6, and TNF-α were observed between the groups. Pg-LPS administration decreased the abundance of Allobacterium in the gut. A predictive metagenomic analysis by PICRUSt2 and STAMP showed that 47 pathways increased and 17 pathways decreased after Pg-LPS administration. Systemic application of periodontal pathogens may cause changes in the intestinal flora which may affect the physiological functions of the intestinal tract.

Gingival Phenotype Changes and the Prevalence of Mucogingival Deformities during the Early Transitional Dentition Phase-A Two-Year Longitudinal Study.

Thin gingival phenotype (GPh) may contribute to periodontal tissue breakdown and recession development. Thus, the early identification of thin GPh in children can allow proper preventive care and the identification of children at risk during orthodontic treatment. The present long-term study aimed to monitor GPh changes, i.e., thickness (GT) and width of attached gingiva (AGW) during the early transitional dentition phase, as well as its potential associations with the mucogingival deformities. Materials and Methods: 83 systematically healthy children were examined twice with an interval of 2 years. Probing depth, GT and AGW at mandibular incisors, vestibular depth, type of lower lip frenum attachment and mucogingival defects were recorded. Results: 95.2% of participants at baseline and 93.9% at 2-year examination expressed thin GPh. During the transition from the deciduous to permanent dentition, GT and AGW declined, but the GT of permanent incisors already erupted at the baseline examination increased in the observation period. Conclusions: Gingival phenotype undergoes changes in the early transitional dentition phase. In spite of the thin gingival phenotype, only single pseudo-recessions and primary shallow vestibule were noticed.

Role of TNF-α in Periodontal Disease &amp; Its Implication on Systemic Health

Periodontal disease is a polymicrobial infection, characterized by gingival inflammation, pocket formation, loss of connective tissue attachment and supporting alveolar bone. Though the etiology of periodontal disease has been established and micro-organisms have been implicated, pathology of these inflammatory lesions have been attributed not only to bacterial products, that have adverse effects on the tissues, but also to chemical mediators released by the host cells, as a result of inflammatory and immune reactions. Oral micro- organisms trigger the endogenous pathways of tissue degradation by activating host cells to produce and release inflammatory mediators and cytokines. These inflammatory mediators and cytokines manifest potent pro-inflammatory and catabolic activity and may play a key role in local amplification of the immune response as well as in periodontal tissue breakdown Apart from playing an important role in periodontal destruction, systemic elevation of TNF –  levels is extremely toxic to the host and hence has been termed as the “Suicide hormone”. TNF – , has been postulated to mediate wasting during chronic infections. This review aims to explore the role of TNF –  in periodontal disease &amp; its implication on systemic health.

Single-Cell RNA Sequencing Identifies New Inflammation-Promoting Cell Subsets in Asian Patients With Chronic Periodontitis.

Periodontitis is a highly prevalent chronic inflammatory disease leading to periodontal tissue breakdown and subsequent tooth loss, in which excessive host immune response accounts for most of the tissue damage and disease progression. Despite of the imperative need to develop host modulation therapy, the inflammatory responses and cell population dynamics which are finely tuned by the pathological microenvironment in periodontitis remained unclear. To investigate the local microenvironment of the inflammatory response in periodontitis, 10 periodontitis patients and 10 healthy volunteers were involved in this study. Single-cell transcriptomic profilings of gingival tissues from two patients and two healthy donors were performed. Histology, immunohistochemistry, and flow cytometry analysis were performed to further validate the identified cell subtypes and their involvement in periodontitis. Based on our single-cell resolution analysis, we identified HLA-DR-expressing endothelial cells and CXCL13+ fibroblasts which are highly associated with immune regulation. We also revealed the involvement of the proinflammatory NLRP3+ macrophages in periodontitis. We further showed the increased cell-cell communication between macrophage and T/B cells in the inflammatory periodontal tissues. Our data generated an intriguing catalog of cell types and interaction networks in the human gingiva and identified new inflammation-promoting cell subtypes involved in chronic periodontitis, which will be helpful in advancing host modulation therapy.

Using FEM to Assess the Effect of Orthodontic Forces on Affected Periodontium

Orthodontic treatment in patients with no periodontal tissue breakdown vs. horizontal bone loss should be approached with caution even though it can bring significant benefits in terms of periodontal recovery and long-term success. We used the finite element method (FEM) to simulate various clinical scenarios regarding the periodontal involvement: healthy with no horizontal bone loss, moderate periodontal damage (33%) and severe horizontal bone loss (66%). Afterwards, forces of different magnitudes (0.25 N, 1 N, 3 N, and 5 N) were applied in order to observe the behavioral patterns. Through mathematical modeling, we recorded the maximum equivalent stresses (σ ech), the stresses on the direction of force application (σ c) and the displacements produced (f) in the whole tooth–periodontal ligament–alveolar bone complex with various degrees of periodontal damage. The magnitude of lingualization forces in the lower anterior teeth influences primarily the values of equivalent tension, then those of the tensions in the direction in which the force is applied, and lastly those of the displacement of the lower central incisor. However, in the case of the lower lateral incisor, it influences primarily the values of the tensions in the direction in which the force is applied, then those of equivalent tensions, and lastly those of displacement. Anatomical particularities should also be considered since they may contribute to increased periodontal risk in case of lingualization of the LLI compared to that of the LCI, with a potential emergence of the “wedge effect”. To minimize periodontal hazards, the orthodontic force applied on anterior teeth with affected periodontium should not exceed 1 N.

Possible Protective Role of NLRC4 Inflammasome in Periodontal Diseases: A Preliminary Study

Introduction: Inflammasomes are multiprotein complexes, which regulate proinflammatory cytokines, Interleukin-18 (IL-18), and Interleukin-1β (IL-1β) that are associated with periodontal breakdown. This study investigated the expression of NOD-like receptor pyrin domain-containing-3 (NLRP3) and NOD-like receptor family CARD domain-containing protein 4 (NLRC4) inflammasomes in different periodontal diseases in humans and their potential association with IL-18 release in gingival crevicular fluid (GCF). Materials and Methods: A total of 45 participants (21 males and 24 females) divided into four groups; periodontally healthy (H), gingivitis (G), chronic periodontitis (CP), and aggressive periodontitis (AgP) based on periodontal examination. NLRC4 and NLRP3 expression were detected by immunohistochemistry in gingival tissue samples for all groups. Expression percentage (%) and staining intensity distribution score (SID) were calculated for both NLRC4 and NLRP3. IL-18 was measured in GCF via enzyme linked immunosorbent assay (ELISA). Results: Positive immunoreactivity was seen for NLRC4 and NLRP3 across groups. No differences were found for NLRC4 expression %, but SID scores were slightly higher in G and AgP compared to other groups (P > 0.05). Results showed a significant increase of NRLP3 expression % in group CP compared to group H (P < 0.05) without affecting SID scores (P > 0.05). IL-18 levels were significantly higher in AgP and CP groups compared to H and G groups (P < 0.05). IL-18 significantly and positively correlated with clinical attachment levels across groups. Conclusion: Within the limitations of this preliminary study, we suggest that the NLRC4 platform may have a protective role contrary to the NLRP3 platform influencing IL-18 release and associated periodontal tissue breakdown.

The role of the IL-33-ST2 axis in the pathogenesis of periodontitis

INTRODUCTION: Periodontitis is a chronic inflammatory disease that arises from an interaction of local dysbiosis in the subgingival biofilm and the host immune response. The disease triggers an inflammatory process that can cause periodontal tissue breakdown. In addition, the production of inflammatory mediators can negatively affect other areas of the body and influence the development and/or severity of associated disorders, including asthma, diabetes and cardiovascular diseases. OBJECTIVE: Conduct a literature review to comprehensively investigate the role of ST2 and IL-33 and the contribution of the IL-33 / ST2 axis in the pathogenesis of periodontitis. METHODS: It is a narrative literature review, which used the databases Pubmed and Academic Google a total of 114 results. RESULTS: A range of immunological markers has been shown to be relevant in the immunopathogenesis of periodontitis, cytokines of the interleukin 1 (IL-1) family, such as IL-1? and IL-33. IL-33, through its ST2 receptor, appears to be involved in the development of periodontitis, acting as a molecule that signals tissue damage from infection and also emits an endogenous signal that activates the immune response and / or worsens bone resorption by activating osteoclastogenesis, either through increases in RANK-L and reduced OPG, or regardless of that pathway. CONCLUSION: The diversity of information contained in the methodologies of these studies hampers attempts to standardize and make correlations between published data, in this sense, the IL-33 / ST2 axis remains a relevant topic in investigations focused on the diagnosis and treatment of periodontal disease.

Local and systemic levels of aMMP-8 in gingivitis and stage 3 grade C periodontitis.

This study aimed to analyze active matrix metalloproteinase (aMMP-8) levels in gingival crevicular fluid (GCF), saliva and serum in the context of new criteria of gingivitis and stage 3 grade C periodontitis. Periodontal disease is an inflammatory process that can result in tooth loss and also is considered a modifying factor for systemic health. Matrix metalloproteinase (MMP)-8 is the major collagenase of periodontal tissue breakdown. Totally 83 systemically healthy and non-smoker individuals consisting of 23 periodontally healthy, 20 gingivitis and 40 stage 3 periodontitis, were recruited to the study. Clinical periodontal examinations of probing depth (PD), clinical attachment loss (CAL), gingival index (GI), plaque index (PI) and bleeding on probing (BOP) were recorded; and GCF, saliva and serum samples were obtained. aMMP-8 was measured by immunofluorometric assay (IFMA). GCF and serum aMMP-8 levels were significantly increased in periodontitis and gingivitis compared to healthy ones (P<.001), whereas gingivitis and periodontitis patients showed similar levels of aMMP-8 in GCF and serum (P>.05). Saliva levels of aMMP-8 were higher in periodontitis patients than both gingivitis and healthy individuals (P<.001). There was no significant difference in salivary aMMP-8 levels between gingivitis group and healthy controls (P>.05). These findings support the involvement of aMMP-8 in periodontal diseases and suggest that its local and systemic levels can reflect stage 3 grade C periodontitis. Moreover, aMMP-8 in GCF and serum seems to have a potential to differentiate between gingivitis and periodontal health.

Prevalence and severity of periodontal disease in a historical Austrian population.

ObjectiveTo assess the prevalence and severity of periodontitis based on different diagnostic methods in a historical Austrian population from the early middle ages.BackgroundThe description of the oral health status of archaeological material can provide interesting insights into prevalence, severity, and extent of oral diseases. Herein, the periodontal health status of the skeletal remains of medieval Avars (700‐800 AD), which were considered as one of the earliest Avarian settlements in Austria, was investigated.MethodsThe skeletal remains of 128 Avars were examined; age and gender were estimated by standard forensic methods and tooth loss and root caries were recorded. Periodontitis was assessed by (a) measurement of the alveolar bone levels (ABL) and (b) evaluation of the interdental septa.ResultsA mean ABL of 4.8 mm was determined, root caries tended to accumulate in teeth with a higher alveolar bone loss, and on average, 6.2 teeth were lost antemortem. Independent of the diagnostic method >90% of the subjects were judged as periodontally diseased, and age and tooth type were significant predictors. However, on the tooth level the presence of periodontitis varied considerably depending on the diagnostic method; that is, 7.6% versus 47.2% of the teeth were judged as healthy based on ABL or interdental septa, respectively.ConclusionThe periodontal status of the skeletal remains of medieval Avars revealed a considerable high prevalence of periodontitis (ie, >90% of this population displayed periodontal tissue breakdown). However, the diagnostic method, disease definition, and data presentation should be considered when comparing results of archaeological material.

Gene Delivery Therapeutics in the Treatment of Periodontitis and Peri-Implantitis: A State of the Art Review.

Background: Periodontal disease is a chronic inflammatory condition that affects supporting tissues around teeth, resulting in periodontal tissue breakdown. If left untreated, periodontal disease could have serious consequences; this condition is in fact considered as the primary cause of tooth loss. Being highly prevalent among adults, periodontal disease treatment is receiving increased attention from researchers and clinicians. When this condition occurs around dental implants, the disease is termed peri-implantitis. Periodontal regeneration aims at restoring the destroyed attachment apparatus, in order to improve tooth stability and thus reduce disease progression and subsequent periodontal tissue breakdown. Although many biomaterials have been developed to promote periodontal regeneration, they still have their own set of disadvantages. As a result, regenerative medicine has been employed in the periodontal field, not only to overcome the drawbacks of the conventional biomaterials but also to ensure more predictable regenerative outcomes with minimal complications. Regenerative medicine is considered a part of the research field called tissue engineering/regenerative medicine (TE/RM), a translational field combining cell therapy, biomaterial, biomedical engineering and genetics all with the aim to replace and restore tissues or organs to their normal function using in vitro models for in vivo regeneration. In a tissue, cells are responding to different micro-environmental cues and signaling molecules, these biological factors influence cell differentiation, migration and cell responses. A central part of TE/RM therapy is introducing drugs, genetic materials or proteins to induce specific cellular responses in the cells at the site of tissue repair in order to enhance and improve tissue regeneration. In this review, we present the state of art of gene therapy in the applications of periodontal tissue and peri-implant regeneration. Purpose: We aim herein to review the currently available methods for gene therapy, which include the utilization of viral/non-viral vectors and how they might serve as therapeutic potentials in regenerative medicine for periodontal and peri-implant tissues.

Aggregatibacter actinomycetemcomitans induces detachment and death of human gingival epithelial cells and fibroblasts via elastase release following leukotoxin-dependent neutrophil lysis.

Aggregatibacter actinomycetemcomitans is considered to be associated with periodontitis. Leukotoxin (LtxA), which destroys leukocytes in humans, is one of this bacterium's major virulence factors. Amounts of neutrophil elastase (NE), which is normally localized in the cytoplasm of neutrophils, are reportedly increased in the saliva of patients with periodontitis. However, the mechanism by which NE is released from human neutrophils and the role of NE in periodontitis is unclear. In the present study, it was hypothesized that LtxA induces NE release from human neutrophils, which subsequently causes the breakdown of periodontal tissues. LtxA-treatment did not induce significant cytotoxicity against human gingival epithelial cells (HGECs) or human gingival fibroblasts (HGFs). However, it did induce significant cytotoxicity against human neutrophils, leading to NE release. Furthermore, NE and the supernatant from LtxA-treated human neutrophils induced detachment and death of HGECs and HGFs, these effects being inhibited by administration of an NE inhibitor, sivelestat. The present results suggest that LtxA mediates human neutrophil lysis and induces the subsequent release of NE, which eventually results in detachment and death of HGECs and HGFs. Thus, LtxA-induced release of NE could cause breakdown of periodontal tissue and thereby exacerbate periodontitis.

Adjunctive Effects of a Sub-Antimicrobial Dose of Doxycycline on Clinical Parameters and Potential Biomarkers of Periodontal Tissue Catabolism.

Objectives: The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of a sub-antimicrobial dose of doxycycline (SDD) in combination with nonsurgical periodontal therapy, compared to nonsurgical periodontal therapy alone, on potential gingival crevicular fluid (GCF) biomarkers of periodontal tissue catabolism related to the clinical outcomes over a 12-month period. Materials and Methods: GCF was collected and clinical parameters were recorded from 30 periodontitis patients randomized either to an SDD or placebo group. The SDD group received SDD (20 mg) b.i.d for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, clinical parameters and GCF sampling were repeated. Matrix metalloproteinase (MMP)-8, MMP-9, MMP-13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase-5 (TRAP-5) were determined by IFMA and ELISA. Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (p < 0.0125) while the SDD group showed significantly better reduction in gingival index (GI) and pocket depth and a gain in clinical attachment compared to the placebo group (p < 0.05). GCF MMP-8 and OPG levels significantly reduced in the SDD group compared to baseline (p < 0.05). GCF MMP-9 significantly decreased in both groups compared to baseline (p < 0.05). GCF MPO significantly decreased at 3 and 9 months in the SDD group, while it significantly decreased at 6 months in the placebo group (p < 0.05). TRAP and MMP-13 could be detected in none of the samples. Conclusions: The present results indicate that three months of adjunctive usage of SDD to nonsurgical periodontal therapy compared to nonsurgical periodontal therapy alone in periodontitis patients results in further improvement of clinical periodontal parameters and GCF markers of periodontal tissue breakdown over a 12-month period. Beneficial effects of adjunctive SDD therapy is likely to be related to the reduced levels of two major periodontitis-associated MMPs, MMP-8 and -9, and their potential oxidative activator MPO.