Objectives: To qualitatively and quantitatively review the use of melatonin as a topical/systemic formulation for the management of periodontitis. Materials and methods: PubMed; Scopus; and Web of Science databases were searched using the MesH terms “melatonin” and “periodontitis”. Title and abstracts were screened to eliminate irrelevant and duplicate articles. The full text data of the screened articles were assessed using the selection criteria. Results: Of 176 identified articles (PubMed-66; Scopus-56; Web of Science-52; Cross-reference-2), only 12 studies qualified to be included in the systematic review. Four studies assessed the independent effect of 1% topical melatonin formulation while 8 articles assessed the adjunctive use of systemic melatonin formulation (1–10 mg) following scaling and root planing (SRP). All studies showed an improvement in periodontal parameters such as pocket depth, clinical attachment loss, periodontal disease index, community periodontal index, gingival bleeding scores, and prognostic marker levels in saliva and serum. A meta-analysis of data from 2 studies revealed that 1–2 mg (systemic) melatonin supplementation reduced pocket depth; although the difference was not statistically significant and hence cannot be interpreted or used for conclusive evidence. Risk of Bias Assessment tool (RoBANS) and Cochrane Collaboration RoB tool elicited a high risk of bias in the included studies. GRADE (recommendation assessment, development, and evaluation) inferred a weak recommendation for the use of melatonin in periodontitis management. Conclusions: Melatonin supplementation (topical and systemic) in periodontitis patients improved key periodontal parameters including pocket depth and clinical attachment loss. Clinical relevance: Melatonin could be a potential host modulatory agent for periodontitis management; although the data from the present review should be interpreted carefully due to the associated high risk of bias.

Periodontal disease is an infection-driven inflammatory disease characterized by the destruction of tooth-supporting tissues. The establishment of chronic inflammation will result in progressive destruction of bone and soft tissue changes. Severe periodontitis can lead to tooth loss. The disease has complex pathogenesis with an interplay between genetic, environmental, and host factors and pathogens. Effective management consists of plaque control and non-surgical interventions, along with adjuvant strategies to control inflammation and disrupt the pathogenic subgingival biofilms. Recent studies have examined novel approaches for managing periodontal diseases such as modulating microbial signaling mechanisms, tissue engineering, and molecular targeting of host inflammatory substances. Mounting evidence suggests the need to integrate omics-based approaches with traditional therapy to address the disease. This article discusses the various evolving and future drug targets, including proteomics, gene therapeutics, vaccines, and nanotechnology in personalized periodontal medicine for the effective management of periodontal diseases.

The present study aims to compare the levels of micro-RNA-146a and micro-RNA-126 in oral subgingival plaque and coronary plaque from artery walls in patients with coronary artery disease who suffer from generalized periodontitis. A total of 75 participants were selected and grouped into three categories of 25 patients each: GP+CAD, GP, and HP groups. GP+CAD consisted of patients diagnosed with generalized periodontitis (GP) and coronary artery disease (CAD). The GP+CAD group was further divided into two groups—GP+CADa: where subgingival plaque samples were collected; GP+CADb group: where coronary plaque samples were collected while the patient underwent a coronary artery bypass grafting surgery. The GP group consisted of 25 patients diagnosed with only generalized periodontitis. The HP group consisted of 25 systemically and periodontally healthy controls. miRNA-146a and miRNA126 levels were assessed in subgingival plaque (SP) samples from all groups. Results revealed that miRNA-146a was expressed at higher levels and miRNA-126 was downregulated in the GP+CAD group. microRNAs in subgingival plaque samples showed a significant correlation with the coronary plaque samples in the GP+CAD group. miRNA-146a and miRNA-126 were present in coronary artery disease patients with periodontitis. These micro-RNAs may serve as risk biomarkers for coronary artery disease and generalized periodontitis.

Background and Objectives: Gingival recession results in adverse aesthetics and root sensitivity, and there is a need to treat and prevent its further progression. To overcome these problems, various advances have been made by clinicians in treating gingival recession based on the type of gingival recession. Miller’s classification has been used for a long time to classify the type of recession. However, certain limitations have been found with use of Miller’s classification such as a lack of clarity in the method for measuring soft and hard tissue loss in the interproximal area. Cairo classification was proposed to overcome limitations of Miller’s classification to classify gingival recession. Cairo’s classification is a treatment-oriented classification based on buccal and interproximal attachment loss. Therefore, the study was conducted to assess and compare the reliability of Miller’s and Cairo’s classifications in determining gingival recession. Material and methods: A total of 220 buccal gingival recession defects were included in the study based on the inclusion and exclusion criteria. Four examiners were included in the study. Two examiners classified the recession defects according to Miller’s classification and the other two examiners classified recession defects according to Cairo’s classification at baseline and at a 1-week interval. Statistical analysis was conducted using SPSS software version 25.0 using Cohen’s kappa correlation coefficient and Chi-square test statistics to determine the intra- and inter-rater agreement among the examiners for the two gingival recession classification systems. A p value of <0.05 was considered statistically significant. Results: The intra-rater agreement for Cairo’s classification was 0.86 and 0.82, whereas for Miller’s classification, it was found to be 0.68. The inter-rater reliability agreement for Cairo’s classification was 0.82 and 0.8, whereas for the Miller’s classification, it was 0.56 and 0.67. Conclusions: Within the limitations of the study, it was found that Cairo’s classification is clearer and more reliable than Miller’s classification in the assessment of gingival recession.

Background: Periodontitis is an inflammatory condition of the tooth-supporting structures initiated and perpetuated by pathogenic bacteria present in the dental plaque biofilm. In periodontitis, immune cells infiltrate the periodontium to prevent bacterial insult. Macrophages derived from monocytes play an important role in antigen presentation to lymphocytes. However, they are also implicated in causing periodontal destruction and bystander damage to the host tissues. Objectives: The objective of the present study was to quantify the cytokine profile of gingival crevicular fluid (GCF) samples obtained from patients with periodontitis. The study further aimed to assess if GCF of periodontitis patients could convert CD14+ monocytes into macrophages of destructive phenotype in an in vitro setting. The secondary objectives of the study were to assess if macrophages that resulted from GCF treatment of monocytes could affect the synthetic properties, stemness, expression of extracellular matrix proteins, adhesion molecules expressed by gingival stem cells, gingival mesenchymal stromal cells, and osteoblasts. Methods: GCF, blood, and gingival tissue samples were obtained from periodontitis subjects and healthy individuals based on specific protocols. Cytokine profiles of the GCF samples were analyzed. CD14+ monocytes were isolated from whole blood, cultured, and treated with the GCF of periodontitis patients to observe if they differentiated into macrophages. Further, the macrophages were assessed for a phenotype by surface marker analysis and cytokine assays. These macrophages were co-cultured with gingival stem cells, epithelial, stromal cells, and osteoblasts to assess the effects of the macrophages on the synthetic activity of the cells. Results: The GCF samples of periodontitis patients had significantly higher levels of IFN gamma, M-CSF, and GM-CSF. Administration of the GCF samples to CD14+ monocytes resulted in their conversion to macrophages that tested positive for CD80, CD86, and CD206. These macrophages produced increased levels of IL-1β, TNF-α, and IL-6. Co-culture of the macrophages with gingival stem cells, epithelial cells, and stromal cells resulted in increased cytotoxicity and apoptotic rates to the gingival cells. A reduced expression of markers related to stemness, extracellular matrix, and adhesion namely OCT4, NANOG, KRT5, POSTN, COL3A1, CDH1, and CDH3 were seen. The macrophages profoundly affected the production of mineralized nodules by osteoblasts and significantly reduced the expression of COL1A1, OSX, and OCN genes. Conclusion: In periodontitis patients, blood-derived monocytes transform into macrophages of a destructive phenotype due to the characteristic cytokine environment of their GCF. Further, the macrophages affect the genotype and phenotype of the resident cells of the periodontium, aggravate periodontal destruction, as well as jeopardize periodontal healing and resolution of inflammation.

Autogenous gingival grafts used for root coverage or gingival augmentation procedures often result in donor site morbidity. Living cellular constructs as an exogenous alternative have been proven to be associated with lower morbidity. With the available background information, the present study aims to assess if quercetin-induced living cell constructs, derived from dental pulp stem cells, have the potential to be applied as a tool for soft tissue augmentation. The characterized dental pulp stem cells (positive for CD73, CD90, and negative for CD34, HLA-DR) were expanded in Dulbecco’s Modified Eagle’s medium (DMEM) supplemented with 10 mM quercetin. The handling properties of the quercetin-induced dental pulp stem cell constructs were assessed by visual, and tactile sensation. A microscopic characterization using hematoxylin and eosin staining, and qRT-PCR-based analysis for stemness-associated genes (OCT4, NANOG, SOX2, and cMyc) was also performed. Dental pulp stem cells without quercetin administration were used as the control. Dental pulp stem cell constructs induced by quercetin easily detached from the surface of the plate, whereas there was no formation in the control cells. It was also simple to transfer the induced cellular construct on the flattened surface. Microscopic characterization of the constructs showed cells embedded in a tissue matrix. Quercetin also increased the expression of stemness-related genes. The use of quercetin-induced DPSC living constructs for soft tissue augmentation could provide an alternative to autogenous soft tissue grafts to lower patient morbidity and improve esthetic outcomes.