Fabrication and Characterization of Decellularized Periodontal Ligament Cell Sheet Constructs.

Decellularized tissue engineered constructs have the potential to promote regeneration by providing a biomimetic extracellular matrix that directs tissue specific regeneration when implanted in situ. Recently, the use of cell sheets has shown promising results in promoting periodontal regeneration. Here, we describe the fabrication of decellularized periodontal cell sheets with intact extracellular matrix structural and biological properties. Melt electro-spun polycaprolactone (PCL) scaffolds are used as a carrier for the inherently fragile cell sheets, in order to provide support during the processes of decellularization. An optimized decellularization method is outlined using perfusion with a combination of NH4OH and Triton X-100 together with a DNase treatment step for DNA removal. The maintenance of extracellular matrix structural and biological integrity is important, and here, we describe the assessment of these properties using immunostaining for extracellular matrix proteins and ELISA for growth factor quantification.

P4 Medicine as a model for precision periodontal care.

OBJECTIVES: P4 Medicine is based on a proactive approach for clinical patient care incorporating the four "pillars" of prediction, prevention, personalization, and participation for patient management. The purpose of this review is to demonstrate how the concepts of P4 medicine can be incorporated into the management of periodontal diseases (particularly periodontitis) termed P4 periodontics. METHODS: This is a narrative review that used current literature to explore how P4 periodontics can be aligned with the 2018 Classification of Periodontal Diseases, current periodontal treatment paradigms, and periodontal regenerative technologies. RESULTS: The proposed model of P4 periodontics is highly aligned with the 2018 Classification of Periodontal Diseases and represents a logical extension of this classification into treatment paradigms. Each stage of periodontitis can be related to a holistic approach to clinical management. The role of "big data" in future P4 periodontics is discussed and the concepts of a treat-to-target focus for treatment outcomes are proposed as part of personalized periodontics. Personalized regenerative and rejuvenative periodontal therapies will refocus our thinking from risk management to regenerative solutions to manage the effects of disease and aging. CONCLUSIONS: P4 Periodontics allows us to focus not only on early prevention and intervention but also allow for personalized late-stage reversal of the disease trajectory and the use of personalized regenerative procedures to reconstruct damaged tissues and restore them to health. CLINICAL SIGNIFICANCE: P4 Periodontics is a novel means of viewing a holistic, integrative, and proactive approach to periodontal treatment.

Localisation of citrullinated and carbamylated proteins in inflamed gingival tissues from rheumatoid arthritis patients.

OBJECTIVES: It has been proposed that citrullination and carbamylation occur in the inflamed periodontium and could be the plausible mechanisms for the generation of antigens involved in the development and progression of RA. The purpose of this study was to determine the presence and location of citrullinated and carbamylated proteins in the gingival tissues and compare their abundance in periodontitis (PD) patients with or without RA. MATERIALS AND METHODS: Gingival tissue samples of healthy (n = 5), PD with RA (n = 5) and PD without RA (n = 5) were collected. Specimens were formalin fixed, paraffin embedded and sectioned at 4 µm. The tissue sections were analysed for the presence of citrullinated and carbamylated proteins by immunohistochemistry. Semi-quantitative analysis was performed to quantify and compare the protein abundance between groups. RESULTS: The number of cells containing citrullinated and carbamylated proteins with higher intensity was markedly increased in gingival tissues from PD with or without RA in comparison with healthy controls. CONCLUSION: Inflamed gingival tissue is a potential source of citrullinated and carbamylated proteins other than synovial tissues. The extent to which the local accumulation of these proteins contributes to the pathogenesis of RA needs further elucidation. CLINICAL RELEVANCE: If PD is a potential source of post-translationally modified proteins, untreated PD should not be taken lightly in the context of RA. Hence, addressing gingival inflammation should be viewed as an important preventive measure in the general population not only for the progression of periodontal disease but also reducing the risk of developing extra-oral comorbidities.

The Nexus Between Periodontal Inflammation and Dysbiosis.

The nexus between periodontal inflammation and the polymicrobial biofilm in the gingival sulcus is critical to understanding the pathobiology of periodontitis. Both play a major role in the etiology and pathogenesis of periodontal diseases and each reinforces the other. However, this nexus is also at the center of a significant conundrum for periodontology. For all mucosal polymicrobial biofilms, the most confounding issue is the paradoxical relationship between inflammation, infection, and disease. Despite significant advances made in both periodontal microbiology and periodontal pathobiology, the issue of which comes first, the inflammatory response or the change to a dysbiotic subgingival microbiota, is still debated. In this paper, we present a model for the pathogenesis of periodontitis based on the central role of inflammation and how this modulates the polymicrobial biofilm within the context of the continuum of health, gingivitis, and periodontitis. We propose a new model termed "Inflammation-Mediated Polymicrobial-Emergence and Dysbiotic-Exacerbation" (IMPEDE), which is designed to integrate into and complement the 2017 World Workshop Classification of Periodontitis.

Probiotic Lactobacillus Rhamnosus GG Protects Against P. Gingivalis And F. Nucleatum Gut Dysbiosis.

OBJECTIVES: This study investigated changes induced by Porphyromonas gingivalis and on gastrointestinal histology and gut microbiome in a mouse model of experimental periodontitis. The effect of probiotic Lactobacillus rhamnosus GG (LGG) in altering these changes was also investigated. METHODS: IThirty-six mice were allocated into six groups. Experimental alveolar bone loss was induced by oral inoculation with P. gingivalis and F. nucleatum. LGG was orally inoculated or orally gavaged. Gastrointestinal tissue changes were assessed using histological analysis and immunohistochemistry. Caecal microbiome was analysed by sequencing 16S rRNA genes of caecal content. RESULTS: Inoculation with P. gingivalis and F. nucleatum induced inflammation throughout gastrointestinal tract (p less than 0.05), increased expression of IL-6 in ileum (p = 0.052) and altered composition of caecal microbiome (p less than 0.05) in experimental mice compared to controls. Mice treated with LGG had reduced tissue inflammation in duodenum (p = 0.044) and lowered levels of IL-6 in ileum (p = 0.048) when compared with disease. LGG therapy influenced gut microbiome changes. CONCLUSION: P. gingivalis and F. nucleatum inoculation induced significant changes in intestinal inflammation and caecal microbiome. Oral gavage with LGG exerted a protective effect against intestinal inflammation and limited gut microbiome changes associated with P. gingivalis and F. nucleatum.

Meeting Report 1st International Academy of Periodontology Research Conference (IAPRC).

The 1st International Academy of Periodontology Research Conference (IAPRC) was successfully held in Giessen, Germany from October 2-4. The objectives of the IAPRC were: to examine the state of the art in periodontal research, to encourage new scientific collaborations and to develop new directions for research.

Biological factors involved in alveolar bone regeneration: Consensus report of Working Group 1 of the 15th European Workshop on Periodontology on Bone Regeneration.

BACKGROUND AND AIMS: To describe the biology of alveolar bone regeneration. MATERIAL AND METHODS: Four comprehensive reviews were performed on (a) mesenchymal cells and differentiation factors leading to bone formation; (b) the critical interplay between bone resorbing and formative cells; (c) the role of osteoimmunology in the formation and maintenance of alveolar bone; and (d) the self-regenerative capacity following bone injury or tooth extraction were prepared prior to the workshop. RESULTS AND CONCLUSIONS: This summary information adds to the fuller understanding of the alveolar bone regenerative response with implications to reconstructive procedures for patient oral rehabilitation. The group collectively formulated and addressed critical questions based on each of the reviews in this consensus report to advance the field. The report concludes with identified areas of future research.

Impact of Severe Chronic Periodontitis on Oral Health-related Quality of Life.

PURPOSE: To assess the impact of extent and severity of chronic periodontitis (CP) on oral health-related quality of life (OHRQoL). MATERIALS AND METHODS: A cross-sectional comparative study was performed on subjects from multiple dental centres in Malaysia using a questionnaire covering sociodemographics, OHRQoL using the Malaysian Oral Health Impact Profile questionnaire, OHIP-14(M) and self-reported symptoms. Participants with severe CP were age-and gender-matched with periodontally healthy/mild periodontitis (HMP) participants based on inclusion and exclusion criteria. Full mouth periodontal examination was performed on participants. Outcome measures were OHIP-14(M) prevalence of impact and severity of impact scores. RESULTS: One hundred and thirty (130) participants comprising 65 severe CP and 65 HMP participants were included in the study. Prevalence of impact on OHRQoL was significantly higher in the severe CP than HMP group, with an odds ratio of 3. Mean OHIP-14(M) score was significantly higher in the severe CP (18.26 ± 10.22) compared to HMP (11.28± 8.09) group. The dimensions of psychological discomfort and functional limitation, and factors such as 'discomfort due to food stuck' and 'felt shy' were impacted more in severe CP compared to HMP group (p < 0.05). When compared with the HMP group, generalised severe CP participants showed higher prevalence of impact on OHRQoL [OR=5] (p < 0.05) compared to localised severe CP [OR=2] (p = 0.05). Participants who had experienced self-reported symptoms had statistically significant impacts on OHRQoL. CONCLUSIONS: Severe CP had a greater impact on OHRQoL compared to HMP. Impacts were mainly for functional limitation and psychological discomfort dimensions. When considering extent of disease, the impact on OHRQoL was mostly in generalised severe CP subgroup.

Lifestyle and periodontitis: The emergence of personalized periodontics.

Personalized medicine is a medical model that involves the tailoring of healthcare - with medical decisions, practices, and/or products being customized to an individual patient. In this model, diagnostic testing is often employed for selecting appropriate and optimal therapies based on the context of a patient's genetic content or other epidemiologic, sociologic, molecular, physiologic, or cellular analyses. With the advent of major advances in periodontal medicine, including genomic discoveries and greater understanding of the multifactorial nature of periodontitis, it seems that the time is ripe to use personalized medicine as a model for personalized periodontics. This volume of Periodontology 2000 explores how new advances in our understanding of periodontitis within a medical model can evolve into new treatment strategies tailor-made for individual patients and not merely based on wholesale treatment paradigms.