Nanoparticles as Strategies for Modulating the Host’s Response in Periodontitis Treatment

D’Amico E., Aceto G.M., Petrini M., Cinquini C., D’Ercole S., Iezzi G., Pierfelice T.V.

Periodontitis is a prevalent inflammatory disease affecting the supporting structures of the teeth, leading to gum recession, tooth loss, and systemic health complications. Traditional diagnostic methods and treatments, such as clinical evaluation and scaling, often fall short in early detection and targeted therapy, particularly in complex or advanced cases. Recent advancements in nanomedicine offer promising solutions for improving both the diagnosis and treatment of periodontitis. Nanoparticles, such as liposomes, quantum dots, and nanorods, have demonstrated potential in enhancing diagnostic accuracy by enabling more precise detection of periodontal pathogens and biomarkers at the molecular level. Furthermore, nanotechnology-based therapies, including drug delivery systems and antimicrobial agents, offer localized and controlled release of therapeutic agents, enhancing efficacy and reducing side effects compared to conventional treatments. This study reviews the current applications of nanomedicine in the diagnosis and treatment of periodontitis, highlighting its potential to revolutionize periodontal care by improving early detection, reducing treatment times, and enhancing therapeutic outcomes.

Wang D., Li Q., Xiao C., Wang H., Dong S.

Kelotte D., Melath A., Kaykool S., Chandran N.

Budală D.G., Luchian I., Tatarciuc M., Butnaru O., Armencia A.O., Virvescu D.I., Scutariu M.M., Rusu D.

Placing antimicrobial treatments directly in periodontal pockets is an example of the local administration of antimicrobial drugs to treat periodontitis. This method of therapy is advantageous since the drug concentration after application far surpasses the minimum inhibitory concentration (MIC) and lasts for a number of weeks. As a result, numerous local drug delivery systems (LDDSs) utilizing various antibiotics or antiseptics have been created. There is constant effort to develop novel formulations for the localized administration of periodontitis treatments, some of which have failed to show any efficacy while others show promise. Thus, future research should focus on the way LDDSs can be personalized in order to optimize future clinical protocols in periodontal therapy.

Zong C., Bronckaers A., Willems G., He H., Cadenas de Llano-Pérula M.

Bioactive nanomaterials are increasingly being applied in oral health research. Specifically, they have shown great potential for periodontal tissue regeneration and have substantially improved oral health in translational and clinical applications. However, their limitations and side effects still need to be explored and elucidated. This article aims to review the recent advancements in nanomaterials applied for periodontal tissue regeneration and to discuss future research directions in this field, especially focusing on research using nanomaterials to improve oral health. The biomimetic and physiochemical properties of nanomaterials such as metals and polymer composites are described in detail, including their effects on the regeneration of alveolar bone, periodontal ligament, cementum and gingiva. Finally, the biomedical safety issues of their application as regenerative materials are updated, with a discussion about their complications and future perspectives. Although the applications of bioactive nanomaterials in the oral cavity are still at an initial stage, and pose numerous challenges, recent research suggests that they are a promising alternative in periodontal tissue regeneration.

Hu D., Zhang C., Sun C., Bai H., Xie J., Gu Y., Li M., Jiang J., Le A., Qiu J., Wang X.

Bacterial infection, biofilm formation, and immune dysfunction are common triggers and aggravators in periodontitis, which render periodontal restoration challenging. Thus, a strategy with antibacterial, anti-inflammatory, and immunoregulatory capacities has great promise in the clinical practice of periodontitis. Herein, carvacrol (CA)-based near-infrared (NIR) light-responsive nano-drug delivery system is developed for the first time. The system consists of upconversion nanoparticles (UCNPs, which upconvert 808 nm NIR to blue light), mesoporous silica (mSiO2, the carrier channel), and hydrophobic CA (blue light response properties). Under the irradiation of 808 nm NIR, owing to the synergy of CA and upconverted blue light, the UCNPs@mSiO2-CA (UCMCs) exhibit the properties of specific anti-bacteria (including anaerobic bacteria), anti-inflammation, and immunomodulation. Notably, high-throughput sequencing results exhibit that many classic inflammatory immune-related signaling pathways, including the MAPK signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway, are enriched to remodel the immune microenvironment. Additionally, UCMCs with NIR irradiation accelerate periodontal restoration and serve as promising non-invasive management of periodontitis. Altogether, this study verifies the feasibility of herbal monomer combined with light-responsive in situ nano-drug delivery system and provides a more effective and reliable strategy for various potential applications of deep tissue diseases.

Li B., Xin Z., Gao S., Li Y., Guo S., Fu Y., Xu R., Wang D., Cheng J., Liu L., Zhang P., Jiang H.

Rationale: Diabetes exacerbates the prevalence and severity of periodontitis, leading to severe periodontal destruction and ultimately tooth loss. Delayed resolution of inflammation is a major contributor to diabetic periodontitis (DP) pathogenesis, but the underlying mechanisms of this imbalanced immune homeostasis remain unclear. Methods: We collected periodontium from periodontitis with or without diabetes to confirm the dysfunctional neutrophils and macrophages in aggravated inflammatory damage and impaired inflammation resolution. Our in vitro experiments confirmed that SIRT6 inhibited macrophage efferocytosis by restraining miR-216a-5p-216b-5p-217 cluster maturation through ''non-canonical'' microprocessor complex (RNA pulldown, RIP, immunostaining, CHIP, Luciferase assays, and FISH). Moreover, we constructed m6SKO mice that underwent LIP-induced periodontitis to explore the in vitro and in vivo effect of SIRT6 on macrophage efferocytosis. Finally, antagomiR-217, a miRNA antagonism, was delivered into the periodontium to treat LIP-induced diabetic periodontitis. Results: We discovered that insufficient SIRT6 as a histone deacetylase in macrophages led to unresolved inflammation and aggravated periodontitis in both human and mouse DP with accumulated apoptotic neutrophil (AN) and higher generation of neutrophil extracellular traps. Mechanistically, we validated that macrophage underwent high glucose stimulation resulting in disturbance of the SIRT6-miR-216/217 axis that triggered impeded efferocytosis of AN through targeting the DEL-1/CD36 axis directly. Furthermore, we demonstrated the inhibitory role of SIRT6 for MIR217HG transcription and identified a non-canonical action of microprocessor that SIRT6 epigenetically hindered the splicing of the primary miR-216/217 via the complex of hnRNPA2B1, DGCR8, and Drosha. Notably, by constructing myeloid-specific deletion of SIRT6 mice and locally delivering antagomir-217 in DP models, we strengthened the in vivo effect of this axis in regulating macrophage efferocytosis and inflammation resolution in DP. Conclusions: Our findings delineated the emerging role of SIRT6 in mediating metabolic dysfunction-associated inflammation, and therapeutically targeting this regulatory axis might be a promising strategy for treating diabetes-associated inflammatory diseases.

Ding Y., Wang Y., Li J., Tang M., Chen H., Wang G., Guo J., Gui S.

Newman K.L., Kamada N.

Inflammatory bowel disease and periodontitis are associated in epidemiologic studies.Both complex conditions involve microbial and host immune system interactions that create chronic inflammation and tissue damage in susceptible individuals.Emerging evidence shows a link between oral inflammation and gut inflammation through direct and indirect mechanisms, including hematologic and lymphatic trafficking of activated T cells and enteric transmission of inflammatory bacteria.There is a need for prospective interventional research to determine the clinical implications of these findings. Both periodontitis and inflammatory bowel disease (IBD) are complex chronic conditions characterized by aberrant host immune response and dysregulated microbiota. Emerging data show an association between periodontitis and IBD, including direct and indirect mechanistic links between oral and intestinal inflammation. Direct pathways include translocation of proinflammatory microbes from the oral cavity to the gut and immune priming. Indirect pathways involve systemic immune activation with possible nonspecific effects on the gut. There are limited data on the effects of periodontal disease treatment on IBD course and vice versa, but early reports suggest that treatment of periodontitis decreases systemic immune activation and that treatment of IBD is associated with periodontitis healing, underscoring the importance of recognizing and treating both conditions. Both periodontitis and inflammatory bowel disease (IBD) are complex chronic conditions characterized by aberrant host immune response and dysregulated microbiota. Emerging data show an association between periodontitis and IBD, including direct and indirect mechanistic links between oral and intestinal inflammation. Direct pathways include translocation of proinflammatory microbes from the oral cavity to the gut and immune priming. Indirect pathways involve systemic immune activation with possible nonspecific effects on the gut. There are limited data on the effects of periodontal disease treatment on IBD course and vice versa, but early reports suggest that treatment of periodontitis decreases systemic immune activation and that treatment of IBD is associated with periodontitis healing, underscoring the importance of recognizing and treating both conditions. The oral–gut axis is an area of emerging interest because of the high burden of oral disease and recent discoveries elucidating the interplay between inflammation, the microbiome (see Glossary), and chronic disease in these related sites [1.Peres M.A. et al.Oral diseases: a global public health challenge.Lancet. 2019; 394: 249-260Abstract Full Text Full Text PDF PubMed Scopus (884) Google Scholar,2.Kitamoto S. et al.The bacterial connection between the oral cavity and the gut diseases.J. Dent. Res. 2020; 99: 1021-1029Crossref PubMed Scopus (72) Google Scholar]. Prior epidemiologic research has identified associations between oral health and a variety of medical conditions [3.Jin L.J. et al.Global burden of oral diseases: emerging concepts, management and interplay with systemic health.Oral Dis. 2016; 22: 609-619Crossref PubMed Scopus (311) Google Scholar]. In this review, we will focus on the relationship between periodontitis and inflammatory bowel disease (IBD). Periodontal disease is characterized by chronic inflammation affecting the bone and tissues around the tooth. This develops initially as gingivitis, a reversible inflammation of the gums and soft tissues around the tooth, and it progresses to involve the bone, cementum, and periodontal ligament. The causes of periodontitis are multifactorial but lead to chronic inflammation with progressive tissue destruction, exposing deeper structures to the oral microbiome, which leads to further host immune activation. Periodontitis is one of the most prevalent conditions worldwide [4.Marcenes W. et al.Global burden of oral conditions in 1990-2010: a systematic analysis.J. Dent. Res. 2013; 92: 592-597Crossref PubMed Scopus (938) Google Scholar]. There is limited high-quality data on the international prevalence and trends in periodontal disease. The global prevalence of periodontitis is estimated to be 11.2% and increases with age [3.Jin L.J. et al.Global burden of oral diseases: emerging concepts, management and interplay with systemic health.Oral Dis. 2016; 22: 609-619Crossref PubMed Scopus (311) Google Scholar, 4.Marcenes W. et al.Global burden of oral conditions in 1990-2010: a systematic analysis.J. Dent. Res. 2013; 92: 592-597Crossref PubMed Scopus (938) Google Scholar, 5.Kassebaum N.J. et al.Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression.J. Dent. Res. 2014; 93: 1045-1053Crossref PubMed Scopus (1072) Google Scholar, 6.Eke P.I. et al.Recent epidemiologic trends in periodontitis in the USA.Periodontol. 2000. 2020; 82: 257-267Crossref PubMed Scopus (116) Google Scholar, 7.Dye B.A. Global periodontal disease epidemiology.Periodontol. 2000. 2012; 58: 10-25Crossref PubMed Scopus (216) Google Scholar]. There is significant variation in prevalence and incidence by region and country. The variability may be attributable to individual-level differences, availability of oral care, methodologic differences between studies, and a lack of nationally representative samples in most countries. Despite these research challenges, data suggest that the prevalence of severe tooth loss (i.e., edentulism) is decreasing while the prevalence of advanced periodontitis is increasing, likely because of increasing longevity and improved preventive dental care that limits tooth loss [4.Marcenes W. et al.Global burden of oral conditions in 1990-2010: a systematic analysis.J. Dent. Res. 2013; 92: 592-597Crossref PubMed Scopus (938) Google Scholar,5.Kassebaum N.J. et al.Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression.J. Dent. Res. 2014; 93: 1045-1053Crossref PubMed Scopus (1072) Google Scholar,8.Kassebaum N.J. et al.Global burden of severe tooth loss: a systematic review and meta-analysis.J. Dent. Res. 2014; 93: 20S-28SCrossref PubMed Scopus (330) Google Scholar]. In the US, an estimated 42% of all community-dwelling adults aged 30 years and older have periodontal disease and 7.8% of the population has severe periodontitis [6.Eke P.I. et al.Recent epidemiologic trends in periodontitis in the USA.Periodontol. 2000. 2020; 82: 257-267Crossref PubMed Scopus (116) Google Scholar]. Longitudinal Scandinavian data show that overall rates of periodontal disease are improving in highly developed countries, though the percentage of the population with severe disease has remained stable [9.Gjermo P.E. Impact of periodontal preventive programmes on the data from epidemiologic studies.J. Clin. Periodontol. 2005; 32: 294-300Crossref PubMed Google Scholar, 10.Hugoson A. et al.Trends over 30 years, 1973-2003, in the prevalence and severity of periodontal disease.J. Clin. Periodontol. 2008; 35: 405-414Crossref PubMed Scopus (165) Google Scholar, 11.Skudutyte-Rysstad R. et al.Trends in periodontal health among 35-year-olds in Oslo, 1973-2003.J. Clin. Periodontol. 2007; 34: 867-872Crossref PubMed Scopus (51) Google Scholar, 12.Ankkuriniemi O. Ainamo J. Dental health and dental treatment needs among recruits of the Finnish defence forces, 1919-91.Acta Odontol. Scand. 1997; 55: 192-197Crossref PubMed Scopus (29) Google Scholar, 13.Kalsbeek H. et al.Trends in periodontal status and oral hygiene habits in Dutch adults between 1983 and 1995.Community Dent. Oral Epidemiol. 2000; 28: 112-118Crossref PubMed Scopus (39) Google Scholar, 14.Demmer R.T. Papapanou P.N. Epidemiologic patterns of chronic and aggressive periodontitis.Periodontol. 2000. 2010; 53: 28-44Crossref PubMed Scopus (189) Google Scholar]. In China, Japan, and India, periodontal disease incidence has increased over the past three decades and in South Korea and Thailand the incidence has decreased [15.Luo L.S. et al.Secular trends in severe periodontitis incidence, prevalence and disability-adjusted life years in five Asian countries: a comparative study from 1990 to 2017.J. Clin. Periodontol. 2021; 48: 627-637Crossref PubMed Scopus (9) Google Scholar]. There are limited data for other regions. IBD is a set of idiopathic chronic inflammatory disorders affecting the gastrointestinal (GI) tract. It includes two main types, Crohn’s disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD is multifactorial, involving both host and environmental factors, such as genetics, diet, stress, and the microbiome [16.Caruso R. et al.Host-microbiota interactions in inflammatory bowel disease.Nat. Rev. Immunol. 2020; 20: 411-426Crossref PubMed Scopus (187) Google Scholar]. CD is characterized by chronic transmural mucosal inflammation that can occur throughout the GI tract from mouth to anus, at times in a discontinuous pattern. Inflammation in UC is limited to the mucosa and occurs in a contiguous fashion in the colon, starting at the rectum, though there can be some involvement of the terminal ileum. The mouth is a common extra-intestinal site of IBD involvement, suggesting a role for the oral–gut immune and microbiome axis in pathogenesis. Previously, CD was felt to be a Th1 cell-predominant process, whereas UC was Th2-driven, though work on Th17 cells has led to a more complex understanding of these diseases [17.Brand S. Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease.Gut. 2009; 58: 1152-1167Crossref PubMed Scopus (492) Google Scholar]. In the USA, IBD affects an estimated 1.3% of adults [18.Dahlhamer J.M. et al.Prevalence of inflammatory bowel disease among adults aged >/=18 years - United States, 2015.MMWR Morb. Mortal. Wkly Rep. 2016; 65: 1166-1169Crossref PubMed Scopus (319) Google Scholar]. Globally, the incidence of IBD varies but has been increasing [19.Mak W.Y. et al.The epidemiology of inflammatory bowel disease: east meets west.J. Gastroenterol. Hepatol. 2020; 35: 380-389Crossref PubMed Scopus (143) Google Scholar,20.Collaborators, G.B.D.I.B.DThe global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol. Hepatol. 2020; 5: 17-30Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar]. In the past 25 years, IBD incidence in highly developed countries has risen slowly or plateaued [21.Shivashankar R. et al.Incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota from 1970 through 2010.Clin. Gastroenterol. Hepatol. 2017; 15: 857-863Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar,22.Bitton A. et al.Epidemiology of inflammatory bowel disease in Quebec: recent trends.Inflamm. Bowel Dis. 2014; 20: 1770-1776Crossref PubMed Scopus (47) Google Scholar]. However in Asia, IBD incidence has increased dramatically, with some countries reporting rates that doubled or tripled in the same time frame [23.Kim H.J. et al.Incidence and natural course of inflammatory bowel disease in Korea, 2006-2012: a nationwide population-based study.Inflamm. Bowel Dis. 2015; 21: 623-630Crossref PubMed Scopus (118) Google Scholar,24.Ng S.C. et al.Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn's and colitis epidemiology study.Gastroenterology. 2013; 145: 158-165Abstract Full Text Full Text PDF PubMed Scopus (537) Google Scholar]. The highest age-standardized prevalence of IBD is in high-income areas of North America (422.0 cases per 100 000), whereas the lowest is in the Caribbean (6.7 per 100 000 population) [20.Collaborators, G.B.D.I.B.DThe global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol. Hepatol. 2020; 5: 17-30Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar]. The mechanisms by which periodontal disease may cause or exacerbate chronic GI diseases are complex. We will discuss the epidemiologic evidence supporting an association between periodontitis and IBD, emerging research on the pathways behind these associations, controversies in the field, and future directions. On an epidemiologic level, multiple studies have demonstrated a strong association between IBD and periodontal disease (Table 1). Three recent meta-analyses found that periodontitis is associated with both CD and UC, with pooled odds ratios of 1.7–3.6 for CD and 2.4–5.4 for UC [25.Lorenzo-Pouso A.I. et al.Association between periodontal disease and inflammatory bowel disease: a systematic review and meta-analysis.Acta Odontol. Scand. 2021; 79: 344-353Crossref PubMed Scopus (12) Google Scholar, 26.She Y.Y. et al.Periodontitis and inflammatory bowel disease: a meta-analysis.BMC Oral Health. 2020; 20: 67Crossref PubMed Scopus (39) Google Scholar, 27.Zhang Y. et al.The association between periodontitis and inflammatory bowel disease: a systematic review and meta-analysis.Biomed. Res. Int. 2021; 20216692420Google Scholar]. This association is seen both in adults as well as children and adolescents with IBD [28.Koutsochristou V. et al.Dental caries and periodontal disease in children and adolescents with inflammatory bowel disease: a case-control study.Inflamm. Bowel Dis. 2015; 21: 1839-1846Crossref PubMed Scopus (40) Google Scholar]. Individuals with IBD are more likely to have had dental treatments and have worse perceived oral health than healthy controls [29.Rikardsson S. et al.Perceived oral health in patients with Crohn's disease.Oral Health Prev. Dent. 2009; 7: 277-282PubMed Google Scholar,30.Kato I. et al.History of inflammatory bowel disease and self-reported oral health: women's health initiative observational study.J. Women's Health (Larchmt). 2020; 29: 1032-1040Crossref PubMed Scopus (2) Google Scholar]. This may be based on a greater need for dental procedures among individuals with IBD as compared with those without IBD, as was found in a Swedish cohort study [31.Johannsen A. et al.Consumption of dental treatment in patients with inflammatory bowel disease, a register study.PLoS One. 2015; 10e0134001Crossref Scopus (15) Google Scholar].Table 1Studies of periodontitis and IBDCountryDesignIBD patients (n)Healthy controls (n)Periodontitis measuresFindingsRefsTaiwanCohort6657 (CD)26 628Billing codesCD patients at increased risk of developing periodontitis (HR 1.36)[68.Chi Y.C. et al.Increased risk of periodontitis among patients with Crohn's disease: a population-based matched-cohort study.Int. J. Color. Dis. 2018; 33: 1437-1444Crossref PubMed Scopus (17) Google Scholar]SwedenCohort3161 (CD) and 2085 (UC)5246Dental care utilizationCD and UC patients had higher numbers of dental procedures following diagnosis, including more total procedures and fillings.[31.Johannsen A. et al.Consumption of dental treatment in patients with inflammatory bowel disease, a register study.PLoS One. 2015; 10e0134001Crossref Scopus (15) Google Scholar]KoreaCohort9 950 548 overall (IBD and no IBD)Oral screening examPeriodontitis associated with increased risk of UC development (aHR 1.091) but not CD (aHR 0.879).[32.Kang E.A. et al.Periodontitis combined with smoking increases risk of the ulcerative colitis: a national cohort study.World J. Gastroenterol. 2020; 26: 5661-5672Crossref PubMed Scopus (11) Google Scholar]TaiwanCohort27 041 periodontal disease108 149 no periodontal diseaseBilling codesHR of IBD in both groups similar (HR 1.01), but increased risk of UC in periodontitis group after adjustment (aHR 1.56)[34.Lin C.Y. et al.Increased risk of ulcerative colitis in patients with periodontal disease: a nationwide population-based cohort study.Int. J. Environ. Res. Public Health. 2018; 15: 2602Crossref Scopus (16) Google Scholar]SwedenCohort20 162 overall (IBD and no IBD)Oral exam at study entryTooth loss at baseline associated with lower risk of IBD development (HR 0.56). More plaque associated with lower CD risk (HR 0.32)[34.Lin C.Y. et al.Increased risk of ulcerative colitis in patients with periodontal disease: a nationwide population-based cohort study.Int. J. Environ. Res. Public Health. 2018; 15: 2602Crossref Scopus (16) Google Scholar]BrazilCross-sectional case-control179 (99 CD and 80 UC)74DMFT, PPD, CAL, BOP, plaque indexMore IBD patients had periodontitis than controls (81.8% CD, 90% UC, 67.6% controls).[79.Brito F. et al.Prevalence of periodontitis and DMFT index in patients with Crohn's disease and ulcerative colitis.J. Clin. Periodontol. 2008; 35: 555-560Crossref PubMed Scopus (91) Google Scholar]JapanCross-sectional case-control60 (18 CD and 42 UC)45BOP, caries, PPDNo difference in periodontitis or caries between IBD and control groups.[37.Imai J. et al.A potential pathogenic association between periodontal disease and Crohn's disease.JCI Insight. 2021; 6e148543Crossref Scopus (6) Google Scholar]GermanyCross-sectional case-control62 (IBD type not specified)59DMFS, caries, plaque index, BOP, PPD, CALNo difference in DMFS between groups but more dental caries and CAL in IBD group.[80.Grossner-Schreiber B. et al.Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: a case-control study.J. Clin. Periodontol. 2006; 33: 478-484Crossref PubMed Scopus (71) Google Scholar]JordanCross-sectional case-control160 (59 CD and 101 UC)100PPD, GR, LA, BOP, plaque index, gingival indexHigher prevalence of periodontitis in IBD group

Kherul Anuwar A.H., Saub R., Safii S.H., Ab-Murat N., Mohd Taib M.S., Mamikutty R., Ng C.W.

This review aimed to evaluate the effectiveness of systemic antibiotics as adjunctive treatment to subgingival debridement in patients with periodontitis. Randomized controlled trials were included that assessed the effectiveness of systemic antibiotics in improving periodontal status, indicated by clinical attachment gain level, probable pocket depth reduction, and bleeding on probing reduction of patients with any form of periodontitis at any follow-up time. Network meta-analyses with a frequentist model using random effects was employed to synthesize the data. The relative effects were reported as mean difference with a 95% confidence interval. Subsequently, all treatments were ranked based on their P-scores. A total of 30 randomized controlled trials were included in this network meta-analyses. Minimally important clinical differences were observed following the adjunctive use of satranidazole, metronidazole, and clindamycin for clinical attachment gain level and probable pocket depth reduction. For bleeding on probing reduction, minimally important clinical differences were observed following the adjunctive use of metronidazole and a combination of amoxycillin and metronidazole. However, the network estimates were supported by evidence with certainty ranging from very low to high. Therefore, the findings of this network meta-analyses should be interpreted with caution. Moreover, the use of these antibiotics adjunct to subgingival debridement should be weighed against possible harm to avoid overuse and inappropriate use of these antibiotics in patients with periodontitis.

Zhang Y., Chen R., Wang Y., Wang P., Pu J., Xu X., Chen F., Jiang L., Jiang Q., Yan F.

Pathogenic dental plaque biofilms are universal and harmful, which can result in oral infections and systemic diseases. Many conventional therapeutic methods have proven insufficient or ineffective against plaque biofilms. Therefore, new strategies are urgently needed. Fusobacterium nucleatum (F. nucleatum), a periodontal pathogen associated with a variety of oral and systemic diseases, is thought to be central to the development and structure of dental plaques. Here, ultra-small gold nanoclusters (AuNCs) were prepared. They exhibited potent antibacterial activity against F. nucleatum through enhanced destruction of bacterial membranes and generation of reactive oxygen species. Furthermore, due to their excellent penetration, the AuNCs could inhibit biofilm formation and destroy mature biofilms in vitro. Their antibiofilm efficacy was further confirmed in a mouse model, where they reduced biofilm accumulation and ameliorated inflammation. Meanwhile, the disruption of oral and gut microbiota caused by colonization of oral F. nucleatum could be partially restored through AuNCs treatment. Therefore, AuNCs could be considered as promising antibiofilm agents and have great potential in the clinical treatment of dental plaque.

Ray R.R.

Periodontitis, being a multifactorial disorder is found to be the most common oral disease denoted by the inflammation of gingiva and resorption of tooth supporting alveolar bone. The disease being closely linked with fast life style and determined by unhygienic behavioural factors, the internal milieu of oral cavity and formation of plaque biofilm on the dental and gingival surfaces. Porphyromonas gingivalis, being the major keystone pathogen of the periodontal biofilm evokes host immune responses that causes damage of gingival tissues and resorption of bones. The biofilm associated microbial community progressively aggravates the condition resulting in chronic inflammation and finally tooth loss. The disease often maintains bidirectional relationship with different systemic, genetic, autoimmune, immunodeficiency diseases and even psychological disorders. The disease can be diagnosed and predicted by various genetic, radiographic and computer-aided design (CAD) & computer-aided engineering (CAE) and artificial neural network (ANN). The elucidation of genetic background explains the inheritance of the disease. The therapeutic approaches commonly followed include mechanical removal of dental plaque with the use of systemic antibiotics. Awareness generation amongst local people, adoption of good practice of timely tooth brushing preferably with fluoride paste or with nanoconjugate pastes will reduce the chance of periodontal plaque formation. Modern tissue engineering technology like 3D bioprinting of periodontal tissue may help in patient specific flawless regeneration of tooth structures and associated bones.

Inchingolo A.D., Inchingolo A.M., Malcangi G., Avantario P., Azzollini D., Buongiorno S., Viapiano F., Campanelli M., Ciocia A.M., De Leonardis N., de Ruvo E., Ferrara I., Garofoli G., Montenegro V., Netti A., et. al.

Phenolic compounds are natural phytochemicals that have recently reported numerous health benefits. Resveratrol, curcumin, and quercetin have recently received the most attention among these molecules due to their documented antioxidant effects. The review aims to investigate the effects of these molecules on bone metabolism and their role in several diseases such as osteopenia and osteoporosis, bone tumours, and periodontitis. The PubMed/Medline, Web of Science, Google Scholar, Scopus, Cochrane Library, and Embase electronic databases were searched for papers in line with the study topic. According to an English language restriction, the screening period was from January 2012 to 3 July 2022, with the following Boolean keywords: (“resveratrol” AND “bone”); (“curcumin” AND “bone”); (“quercetin” AND “bone”). A total of 36 papers were identified as relevant to the purpose of our investigation. The studies reported the positive effects of the investigated phenolic compounds on bone metabolism and their potential application as adjuvant treatments for osteoporosis, bone tumours, and periodontitis. Furthermore, their use on the titanium surfaces of orthopaedic prostheses could represent a possible application to improve the osteogenic processes and osseointegration. According to the study findings, resveratrol, curcumin, and quercetin are reported to have a wide variety of beneficial effects as supplement therapies. The investigated phenolic compounds seem to positively mediate bone metabolism and osteoclast-related pathologies.

Brannon E.R., Guevara M.V., Pacifici N.J., Lee J.K., Lewis J.S., Eniola-Adefeso O.

Acute inflammation is essential for initiating and coordinating the body’s response to injuries and infections. However, in acute inflammatory diseases, inflammation is not resolved but propagates further, which can ultimately lead to tissue damage such as in sepsis, acute respiratory distress syndrome and deep vein thrombosis. Currently, clinical protocols are limited to systemic steroidal treatments, fluids and antibiotics that focus on eradicating inflammation rather than modulating it. Strategies based on stem cell therapeutics and selective blocking of inflammatory molecules, despite showing great promise, still lack the scalability and specificity required to treat acute inflammation. By contrast, polymeric particle systems benefit from uniform manufacturing at large scales while preserving biocompatibility and versatility, thus providing an ideal platform for immune modulation. Here, we outline design aspects of polymeric particles including material, size, shape, deformability and surface modifications, providing a strategy for optimizing the targeting of acute inflammation. Polymeric particle-based therapeutics can target and modulate acute inflammatory diseases. This Review discusses targeting strategies and design mechanisms aimed at mitigating acute inflammation to prevent host tissue damage.

Liu J., Ouyang Y., Zhang Z., Wen S., Pi Y., Chen D., Su Z., Liang Z., Guo L., Wang Y.

Periodontitis and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases with common risk factors, such as long-term smoking, age, and social deprivation. Many observational studies have shown that periodontitis and COPD are correlated. Moreover, they share a common pathophysiological process involving local accumulation of inflammatory cells and cytokines and damage of soft tissues. The T helper 17 (Th17) cells and the related cytokines, interleukin (IL)-17, IL-22, IL-1β, IL-6, IL-23, and transforming growth factor (TGF)-β, play a crucial regulatory role during the pathophysiological process. This paper reviewed the essential roles of Th17 lineage in the occurrence of periodontitis and COPD. The gaps in the study of their common pathological mechanism were also evaluated to explore future research directions. Therefore, this review can provide study direction for the association between periodontitis and COPD and new ideas for the clinical diagnosis and treatment of the two diseases.