Control of tissue homeostasis by the extracellular matrix: Synthetic heparan sulfate as a promising therapeutic for periodontal health and bone regeneration.

Proteoglycans are core proteins associated with carbohydrate/sugar moieties that are highly variable in disaccharide composition, which dictates their function. These carbohydrates are named glycosaminoglycans, and they can be attached to proteoglycans or found free in tissues or on cell surfaces. Glycosaminoglycans such as hyaluronan, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparin/heparan sulfate have multiple functions including involvement in inflammation, immunity and connective tissue structure, and integrity. Heparan sulfate is a highly sulfated polysaccharide that is abundant in the periodontium including alveolar bone. Recent evidence supports the contention that heparan sulfate is an important player in modulating interactions between damage associated molecular patterns and inflammatory receptors expressed by various cell types. The structure of heparan sulfate is reported to dictate its function, thus, the utilization of a homogenous and structurally defined heparan sulfate polysaccharide for modulation of cell function offers therapeutic potential. Recently, a chemoenzymatic approach was developed to allow production of many structurally defined heparan sulfate carbohydrates. These oligosaccharides have been studied in various pathological inflammatory conditions to better understand their function and their potential application in promoting tissue homeostasis. We have observed that specific size and sulfation patterns can modulate inflammation and promote tissue maintenance including an anabolic effect in alveolar bone. Thus, new evidence provides a strong impetus to explore heparan sulfate as a potential novel therapeutic agent to treat periodontitis, support alveolar bone maintenance, and promote bone formation.

Development and External Validation of a Multivariable Prediction Model to Identify Nondiabetic Hyperglycemia and Undiagnosed Type 2 Diabetes: Diabetes Risk Assessment in Dentistry Score (DDS).

The aim of this study was to develop and externally validate a score for use in dental settings to identify those at risk of undiagnosed nondiabetic hyperglycemia (NDH) or type 2 diabetes (T2D). The Studies of Health in Pomerania (SHIP) project comprises 2 representative population-based cohort studies conducted in northeast Germany. SHIP-TREND-0, 2008 to 2012 (the development data set) had 3,339 eligible participants, with 329 having undiagnosed NDH or T2D. Missing data were replaced using multiple imputation. Potential covariates were selected for inclusion in the model using backward elimination. Heuristic shrinkage was used to reduce overfitting, and the final model was adjusted for optimism. We report the full model and a simplified paper-based point-score system. External validation of the model and score employed an independent data set comprising 2,359 participants with 357 events. Predictive performance, discrimination, calibration, and clinical utility were assessed. The final model included age, sex, body mass index, smoking status, first-degree relative with diabetes, presence of a dental prosthesis, presence of mobile teeth, history of periodontal treatment, and probing pocket depths ≥5 mm as well as prespecified interaction terms. In SHIP-TREND-0, the model area under the curve (AUC) was 0.72 (95% confidence interval [CI] 0.69, 0.75), calibration in the large was -0.025. The point score AUC was 0.69 (95% CI 0.65, 0.72), with sensitivity of 77.0 (95% CI 76.8, 77.2), specificity of 51.5 (95% CI 51.4, 51.7), negative predictive value of 94.5 (95% CI 94.5, 94.6), and positive predictive value of 17.0 (95% CI 17.0, 17.1). External validation of the point score gave an AUC of 0.69 (95% CI 0.66, 0.71), sensitivity of 79.2 (95% CI 79.0, 79.4), specificity of 49.9 (95% CI 49.8, 50.00), negative predictive value 91.5 (95% CI 91.5, 91.6), and positive predictive value of 25.9 (95% CI 25.8, 26.0). A validated prediction model involving dental variables can identify NDH or undiagnosed T2DM. Further studies are required to validate the model for different European populations.

Concordance of three point of care testing devices with clinical chemistry laboratory standard assays and patient-reported outcomes of blood sampling methods.

BACKGROUND: Point of care testing (POCT) devices have been developed to facilitate immediate results with the potential to aid screening for new disease and enable patients to self-monitor their disease. Non-communicable diseases (NCDs) are the major cause of mortality globally and are increasing in prevalence as the population ages. Allied health care professionals (AHPs) are skilled in undertaking risk assessment and delivering preventative advice, providing opportunities to access large proportions of the population who may not visit their doctor, within non-traditional community settings. There is evidence of high levels of support from public, patients and health professionals for engaging AHPs in risk-targeted early case detection of certain NCDs. Thus, POCT devices offer a potential alternative to traditional venous blood collection, as novel care pathways for increasing early case detection and access to preventative care. The objectives of this study were to: (i) determine the concordance of the specific POCT devices with laboratory-based standard assays employed within clinical biochemistry laboratories. (ii) compare the sampling experience of both methods via patient-reported experiences. METHODS: A prospective, two-centre study was undertaken involving 158 participants who provided informed consent. Venous blood was collected for traditional assays of HbA1c, creatinine/ estimated Glomerular-Filtration-Rate (eGFR) and vitamin-D. Capillary blood was collected by finger prick test and also assayed for the same biochemical indices (Nova StatSensor (creatinine/eGFR); Siemens DCA-Vantage (HbA1C); CityAssays (vitamin-D)). All users were provided with device training. Participants reported any discomfort experienced by each simultaneously applied method (randomised in order) via a 100 mm Visual-Analogue-Scale. RESULTS: Results for each POCT device and the laboratory standard were analysed by Bland-Altman plots to determine assay concordance. POCT devices demonstrated good concordance with laboratory testing, with at least 95% of all samples being within two standard deviations, for each of the devices tested. The majority of participants reported less discomfort with POCT than venepuncture, with the average reported discomfort being 17/100 mm less for POCT compared to venous blood sample collection on the visual analogue scale. CONCLUSIONS: The POCT devices demonstrated acceptable concordance with laboratory-based assays, and patients reported lower levels of discomfort compared to traditional means of blood collection. This study demonstrates the potential of using these devices as acceptable methods for opportunistic testing of "at-risk" individuals within non-traditional community care settings.

COVID-19: Seroprevalence and Vaccine Responses in UK Dental Care Professionals.

Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory.

Periodontitis and Cardiovascular Diseases. Consensus Report.

Background: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. Material and Methods: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations. Results and Conclusions: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

Attitudes towards Oral Health in Patients with Rheumatoid Arthritis: A Qualitative Study Nested within a Randomized Controlled Trial.

INTRODUCTION: Patients with rheumatoid arthritis (RA) present a higher incidence and severity of periodontitis than the general population. Our study, Outcomes of Periodontal Treatment in Patients with Rheumatoid Arthritis (OPERA), was a randomized waiting-list controlled trial using mixed methods. Patients randomized to the intervention arm received intensive periodontal treatment, and those in the control arm received the same treatment with a 6-mo delay. AIM: The nested qualitative component aimed to explore patients' experiences and priorities concerning oral health and barriers and facilitators for trial participation. METHODS: Using purposive sampling until thematic saturation was reached, we conducted 21 one-to-one semistructured interviews with randomized patients in either of the 2 treatment arms as well as with patients who did not consent for trial participation. RESULTS: The patients described their experiences about RA, oral health, and study participation. Previous experiences with dental care professionals shaped patients' current perceptions about oral health and the place of oral health on their list of priorities compared with other conditions. Patients also highlighted some of the barriers and facilitators for study participation and for compliance with oral health maintenance. The patients, in the control arm, presented their views regarding the acceptable length of waiting time for the intervention. CONCLUSION: The associations between periodontal and systemic health are increasingly recognized by the literature. Our study provided an insight into RA patients' experiences and perceptions about oral health. It also highlighted some of the barriers and facilitators for participating in a periodontal interventional study for this group. We hope that our findings will support the design of larger interventional periodontal studies in patients with RA. The complex challenges faced by the burden of RA and the associated multimorbidities in this patient group might highlight opportunities to improve access to oral health services in this patient population. KNOWLEDGE TRANSFER STATEMENT: This article provided insights into the experiences and perceptions of rheumatoid arthritis patients about their oral health to improve patient participation in a definitive clinical trial.

Periodontal diagnosis in the context of the 2017 classification system of periodontal diseases and conditions: presentation of a patient with periodontitis localised to the molar teeth.

The objective of this case report is to illustrate the diagnosis and classification of periodontitis, according to the 2017 classification system, as recommended in the British Society of Periodontology (BSP) implementation plan. A 37-year-old female was diagnosed with periodontitis (molar-incisor pattern), stage III, grade C, currently unstable. Several issues pertinent to the diagnosis of localised forms of periodontitis in young patients are discussed in relation to the current and previous classification systems. Periodontitis can be limited to a few sites and this case highlights the importance of the careful application of the basic periodontal examination (BPE).

Periodontal diagnosis in the context of the 2017 classification system of periodontal diseases and conditions: Presentation of a middle-aged patient with localised periodontitis.

The objective of this case report is to illustrate the diagnosis and classification of periodontitis according to the 2017 classification system as recommended in the British Society of Periodontology (BSP) implementation plan. We describe a case of a patient who was diagnosed with 'localised periodontitis; stage II, grade B; currently unstable'. The present case report presents an example for the application of the new classification system and illustrates how the new classification system captures disease severity, extent and disease susceptibility by staging and grading periodontitis.

A randomised clinical study comparing the effect of Steareth 30 and SLS containing toothpastes on oral epithelial integrity (desquamation).

OBJECTIVE: To compare the clinical effect of toothpastes containing Steareth 30 and SLS (sodium lauryl sulphate) surfactants on oral epithelial integrity (desquamation) using a new Oral Mucosal Sloughing Index (OMSI). METHODS: 30 volunteers participated in a single centre, double-blind, randomised, crossover clinical study. After a lead-in, subjects were allocated to the first test toothpaste, which was applied to the maxilla via a cap splint, followed by whole mouth brushing with the respective toothpaste and rinsing with the toothpaste slurry. Soft desquamation (lesion status) was assessed using a novel Oral Mucosal Sloughing Index (OMSI). Soft tissue status was measured at baseline (prior to test product use), 30 min following test product application and 4 days later following "at home" use of test toothpaste. After a wash out period, soft tissue assessment and product use were repeated for the remaining toothpaste. RESULTS: Using the OMSI, 30 min post-application, significantly fewer lesion counts (all sites) were observed for the Steareth 30 toothpaste compared to SLS toothpaste (p < 0.0001). Additionally, 30 min after toothpaste use, the average lesion severity score was significantly lower for the Steareth 30 toothpaste compared to SLS toothpaste (p < 0.0001). There were no significant differences in lesion status at baseline or following 4 days of "at home" use of the toothpastes. No product related adverse events were reported. CONCLUSION: Using an Oral Mucosal Sloughing Index for assessment, application of a toothpaste containing Steareth 30 generated significantly less transient soft tissue desquamation (fewer lesion counts and lower severity) than a toothpaste containing SLS. CLINICAL SIGNIFICANCE: Treatment with a toothpaste containing Steareth 30 surfactant generated fewer transient soft tissue lesions (lower desquamation) compared to a toothpaste containing SLS surfactant.

Periodontal diagnosis in the context of the 2017 classification system of periodontal diseases and conditions - implementation in clinical practice.

The 2017 World Workshop Classification system for periodontal and peri-implant diseases and conditions was developed in order to accommodate advances in knowledge derived from both biological and clinical research, that have emerged since the 1999 International Classification of Periodontal Diseases. Importantly, it defines clinical health for the first time, and distinguishes an intact and a reduced periodontium throughout. The term 'aggressive periodontitis' was removed, creating a staging and grading system for periodontitis that is based primarily upon attachment and bone loss and classifies the disease into four stages based on severity (I, II, III or IV) and three grades based on disease susceptibility (A, B or C). The British Society of Periodontology (BSP) convened an implementation group to develop guidance on how the new classification system should be implemented in clinical practice. A particular focus was to describe how the new classification system integrates with established diagnostic parameters and pathways, such as the basic periodontal examination (BPE). This implementation plan focuses on clinical practice; for research, readers are advised to follow the international classification system. In this paper we describe a diagnostic pathway for plaque-induced periodontal diseases that is consistent with established guidance and accommodates the novel 2017 classification system, as recommended by the BSP implementation group. Subsequent case reports will provide examples of the application of this guidance in clinical practice.

Periodontal diagnosis in the context of the BSP implementation plan for the 2017 classification system of periodontal diseases and conditions: presentation of a pair of young siblings with periodontitis.

The objective of this case report is to illustrate the diagnosis and classification of periodontitis according to the 2017 classification system as recommended in the British Society of Periodontology (BSP) implementation plan. We describe two cases in the form of a pair of siblings, who developed periodontitis very early in life. A 19-year-old female was diagnosed with 'generalised periodontitis; stage III/grade C; currently unstable'. Her 14-year-old sister was diagnosed with 'localised periodontitis; stage II, grade C; currently unstable'. The present case report presents an example for the application of the new classification system and illustrates the importance of a periodontal check for children and adolescents and/or their relatives.

Cigarette smoke modifies neutrophil chemotaxis, neutrophil extracellular trap formation and inflammatory response-related gene expression.

BACKGROUND AND OBJECTIVE: Cigarette smoking is a major risk factor for periodontitis, and smoking perturbs neutrophil reactive oxygen species production. This study tested the hypothesis that cigarette smoke extract (CSE) and its components/metabolites nicotine, cotinine and thiocyanate (SCN-), may influence neutrophil functions. MATERIAL AND METHODS: Chemotaxis was assessed in neutrophils pre-treated with CSE using real-time video microscopy. Neutrophil extracellular trap (NET) release in response to CSE, nicotine, cotinine, SCN- as well as to phorbol 12-myristate-13-acetate and hypochlorous acid following pre-treatment with CSE, nicotine, cotinine or SCN- was assessed using fluorescence-based assays. The impact of CSE and SCN- treatment on neutrophil respiratory burst- and inflammation-related gene expression (NFKBIE, DNAJB1, CXCL8, NCF1, NCF2, CYBB) was determined by real-time polymerase chain reaction. RESULTS: Both CSE and SCN- pre-treatment inhibited phorbol 12-myristate-13-acetate-stimulated NET release. Additionally, SCN- inhibited hypochlorous acid-stimulated NET formation, while SCN- alone stimulated NET release. Overall, neutrophils pre-treated with CSE exhibited reduced speed, velocity and directionality relative to untreated neutrophils. Although CSE and SCN- promoted DNAJB1 expression, increased redox-related gene expression was only detected in response to SCN-. CONCLUSION: These results suggest that CSE can alter ex vivo neutrophil activation by mechanisms independent of SCN- and nicotine, and SCN- may contribute to the perturbed innate immune responses observed in smokers.

TiO2 nanoparticles can selectively bind CXCL8 impacting on neutrophil chemotaxis.

The interaction between TiO2 nanoparticles (NPs) and inflammatory cytokines, including CXCL8, a clinically relevant pro-inflammatory chemokine was investigated. TiO2 is present in tissues adjacent to failing implanted Ti (titanium) devices. TiO2 NPs were shown to bind to CXCL8 in vitro, causing perturbation of quantification of CXCL8 by ELISA, in both simple and complex protein panels, in a dose-dependent manner. Binding between TiO2 NPs and CXCL8 was demonstrated by protein gel electrophoresis. TiO2 NPs were also shown to inactivate the chemoattractant property of CXCL8 in a dose-dependent manner, suggesting that the binding between TiO2 NPs and CXCL8 is likely to be clinically relevant. The results of this study disputed the applicability of detection of CXCL8 by ELISA in systems where TiO2 NPs were present. Clinically, the disruption of chemotaxis of neutrophils in response to CXCL8 in the presence of TiO2 might mean a hampered immune response to inflammation in tissues containing TiO2 NPs.

Practitioner evaluation of an online oral health and risk assessment tool for young patients.

Aim To test the validity and acceptability of an online oral health assessment and biofeedback tool for young patients (under 17) for use in general dental practice.Methods A convenience sample of thirteen practitioners were recruited to test the functionality of a novel version of the Denplan PreViser Patient Assessment tool (DEPPA) developed for young patients (YDEPPA). Dentists who had completed eight or more assessments during a one month window were sent a link to an online feedback survey, comprising eight statements about YDEPPA, with scoring options of 0-10, where a score of 10 indicated complete agreement with the relevant questions. Verbatim comments were encouraged. The clinical data submitted were held in a central database in an encrypted format so that only the user practice could identify individual patients.Results Twelve practitioners completed eight or more assessments and were included in the survey. A total of 175 patient assessments were received. Ten practitioners completed the on-line survey. The statement 'YDEPPA produces a valid measurement of each patient's oral health' received an average feedback score of 8.8. The statement 'The full YDEPPA report is a valuable communication aid' received a score of 9.6. Feedback was generally very positive with all scores >8.2. Constructive critical feedback was received for the caries risk aspect of the YDEPPA protocol, with suggestions made for improving objectivity of data inputs. Eighty-one percent of the verbatim comments received were positive.Conclusions Once the caries risk issues raised by pilot dentists have been addressed, YDEPPA appears suitable as a pragmatic analytical and biofeedback tool for use in general dental practice to assess the oral health of young patients, and to facilitate education and engagement of young patients and their parents/carers in positive health behaviours.

The oral microbiome - an update for oral healthcare professionals.

For millions of years, our resident microbes have coevolved and coexisted with us in a mostly harmonious symbiotic relationship. We are not distinct entities from our microbiome, but together we form a 'superorganism' or holobiont, with the microbiome playing a significant role in our physiology and health. The mouth houses the second most diverse microbial community in the body, harbouring over 700 species of bacteria that colonise the hard surfaces of teeth and the soft tissues of the oral mucosa. Through recent advances in technology, we have started to unravel the complexities of the oral microbiome and gained new insights into its role during both health and disease. Perturbations of the oral microbiome through modern-day lifestyles can have detrimental consequences for our general and oral health. In dysbiosis, the finely-tuned equilibrium of the oral ecosystem is disrupted, allowing disease-promoting bacteria to manifest and cause conditions such as caries, gingivitis and periodontitis. For practitioners and patients alike, promoting a balanced microbiome is therefore important to effectively maintain or restore oral health. This article aims to give an update on our current knowledge of the oral microbiome in health and disease and to discuss implications for modern-day oral healthcare.

Birmingham's new dental school and hospital - A real Peter Pan of dentistry.

A look at the history of Birmingham Dental Hospital which, since it was first founded in 1858 as Birmingham Dental Dispensary, has moved six times, the sixth move being to its new Pebble Mill site on 1 April 2016.

The relationship between general health and lifestyle factors and oral health outcomes.

Aim The primary research question addressed in this paper was 'are lower than average oral health scores observed for those patients who report problems with general health and high-risk lifestyle factors?'Methods A population analysis was conducted on the first 37,330 patients, assessed by 493 dentists in the UK, to receive a Denplan PreViser Patient Assessment (DEPPA) at their dental practice. The Oral Health Score (OHS) was generated using a mixture of patient-reported factors and clinical findings and is an integrated component of DEPPA. Patients' self-reported risk factors included diabetes status, tobacco use and alcohol consumption. Patients' general health was measured by self-report, that is, a yes/no answer to the question 'have you experienced any major health problems in the last year for example a stroke, heart attack or cancer?' Multivariable linear regression analysis was employed to study the association between the OHS and general health and risk factors for patients in the DEPPA cohort.Results The mean age of participants was 54 years (range 17-101; S.D. 16 years) and the mean OHS for the group was 78.4 (range 0-100; S.D. 10). 1,255 (3%) of patients reported experiencing a major health problem in the previous year. In the fully adjusted model, diabetes, tobacco use, excessive alcohol consumption (three or more drinks per day), and poor overall health in the preceding year were all associated with a statistically significant drop in the mean OHS of patients. Having diabetes was associated with a 1.7 point (95% CI 1.3-2.1, P <0.001) drop in OHS, tobacco use was associated with a 2.7 point (95% CI 2.5-2.9, P <0.001) drop in OHS, and excessive alcohol consumption was associated with a 1.8 point (95% CI 1.3-2.4, P <0.001) drop in OHS. The mean OHS in patients who reported a major health problem in the preceding year was 0.7 points (95% CI 0.2-1.2, P = 0.006) lower than that of patients who did not report a major health problem in the preceding year.Conclusion The current study has demonstrated that patient reported general health and risk factors were negatively associated with an overall composite oral health score outcome in a large population of over 37,000 patients examined by 493 dentists. While the clinical significance of some of the reported associations is unknown, the data lend support to the growing body of evidence linking the oral and systemic health of individuals. Therefore, GDPs may be in a unique position to influence the lifestyle and general health of patients as part of their specific remit to attain and maintain optimal oral health.

Neutrophil Extracellular Traps in Periodontitis: A Web of Intrigue.

Neutrophil extracellular traps (NETs) represent a novel paradigm in neutrophil-mediated immunity. NETs are believed to constitute a highly conserved antimicrobial strategy comprising decondensed nuclear DNA and associated histones that are extruded into the extracellular space. Associated with the web-like strands of DNA is an array of antimicrobial peptides (AMPs), which facilitate the extracellular destruction of microorganisms that become entrapped within the NETs. NETs can be released by cells that remain viable or following a unique form of programmed cell death known as NETosis, which is dependent on the production of reactive oxygen species (ROS) and the decondensing of the nuclear DNA catalyzed by peptidyl arginine deiminase-4. NETs are produced in response to a range of pathogens, including bacteria, viruses, fungi, and protozoa, as well as host-derived mediators. NET release is, however, not without cost, as the concomitant release of cytotoxic molecules can also cause host tissue damage. This is evidenced by a number of immune-mediated diseases, in which excess or dysfunctional NET production, bacterial NET evasion, and decreased NET removal are associated with disease pathogenesis. Periodontitis is the most prevalent infectious-inflammatory disease of humans, characterized by a dysregulated neutrophilic response to specific bacterial species within the subgingival plaque biofilm. Neutrophils are the predominant inflammatory cell involved in periodontitis and have previously been found to exhibit hyperactivity and hyperreactivity in terms of ROS production in chronic periodontitis patients. However, the contribution of ROS-dependent NET formation to periodontal health or disease remains unclear. In this focused review, we discuss the mechanisms, stimuli, and requirements for NET production; the ability of NET-DNA and NET-associated AMPs to entrap and kill pathogens; and the potential immunogenicity of NETs in disease. We also speculate on the potential role of NETs in the pathogenesis of periodontitis.