- Please check and comment entries here.
Periodontitis and Systemic Disorder
Periodontitis, a major oral disease, affects a vast majority of the population but has been often ignored without realizing its long-fetched effects on overall human health. A realization in recent years of its association with severe diseases such as carditis, low birth weight babies, and preeclampsia has instigated dedicated research in this area. In the arena of periodontal medicines, the studies of past decades suggest a link between human periodontal afflictions and certain systemic disorders such as cardiovascular diseases, diabetes mellitus, respiratory disorders, preterm birth, autoimmune disorders, and cancer. Although, the disease appears as a locoregional infection, the periodontal pathogens, in addition their metabolic products and systemic mediators, receive access to the bloodstream, thereby contributing to the development of systemic disorders. Mechanism-based insights into the disease pathogenesis and association are highly relevant and shall be useful in avoiding any systemic complications.
2. Possible Mechanism behind the Systemic Manifestations of Periodontitis
Oral-hematogenous migration of periodontal pathogens and its direct effects to target organs .
Transtracheal migration of periodontal pathogens and its direct effects to target organs.
Oral-hematogenous migration of inflammatory mediators such as cytokines and antibodies with their effects on distant organs.
3. Periodontitis and Systemic Complications
3.1. Periodontitis and Cardiovascular Diseases
3.1.2. Coronary Heart Disease
3.2. Periodontitis and Autoimmune Disorders
3.3. Periodontitis and Respiratory Disorder
3.4. Periodontitis and Diabetes Mellitus
3.4.1. Periodontitis as a Consequence of Diabetes
3.4.2. Diabetes as a Complication of Periodontitis
3.5. Periodontitis and Pre-Term Low Birth Weight Babies
3.6. Periodontitis and Cancer
Periodontal pathogens induce chronic inflammation; this promotes already initiated cells, leading to uncontrolled cell growth and potential carcinogenesis.
Periodontopathic bacteria may also have a more direct role through local inflammatory responses and carcinogenic transformations. Helicobacter pylori infection is an example of this.
Chronic periodontal disease may suggest that an individual’s immune system is compromised, unable to clear the infection, and consequently deficient at surveillance for tumor growth.
Periodontal inflammation can lead to genetic alteration via the production of reactive oxygen and nitrogen species-type oxidizing compounds.
Carcinogenesis and wound healing shared several common biological processes and carcinogenesis can be considered as an unregulated form of wound healing.
Failure of the periodontal inflammation-resolving mechanism.
4. Current Treatment Modalities and Advanced Pharmaceutical Approach
|Nanofibrous scaffolds||Silver nanoparticles, AgNPs and hydroxyapatite nanoparticles, and HANPs electrospun to prepare nanofibrous composites based on polylactic acid/cellulose acetate (PLA/CA) or polycaprolactone (PCL) polymers||Periodontal tissue and bone regeneration||Biodegradable electrospun nanoparticles-in-nanofibers-based scaffolds for guided tissue regeneration (GTR) and guided bone regeneration (GBR) with enhanced mechanical properties, cell adhesion, biocompatibility, and antibacterial properties||In-vitro studies of nanofibrous films cut into 10 × 10 mm2 samples showed that the addition of HANPs improved the cell viability by about 50 and AgNPs provided sustained antibacterial activity (40 mm zone of inhibition diameter) for 32 days. Additionally, the nanofibrous scaffolds offer optimum mechanical properties, tensile modulus (20–38 MPa), and a desirable degradation profile (40–70% of its mass in eight weeks).|||
coupled with calcium-binding bone morphogenetic protein 2 (BMP-2)
|Alveolar bone regeneration||Mineralized nanofiber segments (20 μm) coupled with BMP-2, mimicking peptides for periodontal bone regeneration||In animal studies, the mineralized nanofibers were implanted into critical-sized maxillary defects of 2 mm in diameter and 2 mm in depth in rats and a sustained release profile was recorded for over four weeks. X-ray microcomputed tomography (μ-CT) analysis revealed ~3 times greater new bone volume and mineral density.|||
|Polymeric fibers||Electrospun nanofibers encapsulation BAR using poly (lactic-co-glycolic acid) (PLGA), poly (L-lactic acid) (PLLA), and polycaprolactone (PCL) either as a single or blended solution with polyethylene oxide (PEO)||Inhibition of Porphyromonas gingivalis and adherence to Streptococcus gordonii||Rapid-release polymeric electrospun nanofibers against P. gingivalis/S. gordonii biofilms in-vitro||The most promising formulation of 10:90 PLGA: PEO of electrospun nanofibers has demonstrated a 95% BAR release after 4 h, a dose-dependent inhibition of biofilm formation (IC50 = 1.3 μM), disruption of established dual-species biofilms (IC50 = 2 μM), and maintenance of high-cell viability.|||
|Nanofibrous membrane||PLLA/gelatin||Periodontal tissue regeneration||Biodegradable multifunctional nanofibrous membrane prepared by electrospinning biodegradable polymers with magnesium oxide nanoparticles (nMgO) for periodontal tissue regeneration and high antibacterial capacity||In-vitro results showed that incorporating nMgO into poly (lactic acid) (PLA)/gelatin elevates the tensile strength to maintain structural stability and adjust the degradation rate for periodontal regeneration. Considerable antibacterial and osteogenic properties were also observed. The in-vivo investigations in a rat periodontal defect model demonstrated effective periodontal tissue regeneration guided via nMgO-incorporated membranes.|||
|Polymeric films||PLLA/PCL blends containing propolis||Guided periodontal tissue regeneration||Biodegradable composite membranes produced from PCL/PLLA blends with a natural antibacterial extract (propolis) as novel periodontal barrier membrane||The in-vitro antibacterial studies revealed remarkable activities against Staphylococcus aureus (17 mm zone of inhibition). The prepared films also showed faster degradation in physiological conditions.|||
|Biopolymer composite film||Curcumin||Topical patches for wound care, periodontitis, and oral cancer treatment||Multifunctional biopolymer composites based on curcumin-loaded bacterial cellulose/alginate/gelatin||The in-vitro studies have shown substantial antibacterial activity against E. coli and S. aureus infection. The purported composite films exhibited cytotoxicity to human keratinocytes and human gingival fibroblasts, and also show potent anticancer activity in oral cancer cells.|||
|Regenerative scaffolds||Cellulose hydrogels and biopolymers derived from plants, and Larrea tridentate||Periodontal tissue regeneration||Cellulose hydrogel films enriched with LT for biomedical application in wound healing and as regenerative scaffolds||For in-vitro studies, NIH3T3 mouse embryonic cells were used for the measurements of cell viability and morphology assays. For in-vivo assays, hydrogel films were implanted intramuscularly into female Wistar rats (250 g weight; 2 months), to analyze their cytocompatibility and biocompatibility.|||
|Nanofibrous membrane||PLGA/gelatin, dexamethasone (osteogenic), and doxycycline hyclate (anti-bacterial agent)||Guided bone regeneration||Bi-layered electrospun composite nano-membrane with combined osteogenic and antibacterial properties for guided bone regeneration||In-vitro studies indicated that both dexamethasone and doxycycline hyclate followed a favorable sustained drug release profile. The cell viability evaluation suggested good cytocompatibility. The osteogenesis analyses demonstrated an enhanced osteoinductive capacity for rat bone marrow stem cells, increased alkaline phosphatase activity, enhanced calcium deposition, and upregulated osteocalcin expression. Furthermore, the antimicrobial experiments revealed effective antibacterial potency.|||
|Hydrogel||Polyacrylic acid (PAA) hydrogel containing metronidazole||Therapeutic dressing||Gamma-ray irradiation targeted metronidazole-loaded PAA hydrogel||The in-vitro cytocompatibility test was performed according to ISO 10993-5 and the formulation exhibited no cytotoxicity. The antibacterial activity against E. coli (ATCC 43895), S. aureus (ATCC 14458), and S. mutans (ATCC 25175) yielded satisfactory results. In release studies, metronidazole from the PAA hydrogel was consistently released and reached approximately 80% at 120 min.|||
lipoxin and poly isocyano peptide (PIC)
|Periodontal||Antimicrobial and anti-inflammatory thermo-reversible hydrogel for improved gingival clinical attachment and periodontal drug delivery||The formulations were characterized in-vitro and in dogs with naturally occurring periodontitis. The results showed that the prepared hydrogel could be easily injected into periodontal pockets due to the thermo-reversible nature of the material. The formulation yielded significant release with no local or systemic adverse effects. A reduced subgingival bacterial load, pro-inflammatory interleukin-8 level, and improved gingival clinical attachment by 0.6 mm was also observed.|||
|Periodontal||A randomized, double-blind, cross-over, and placebo-controlled clinical trial of liposomal gel (intra pocket) for non-invasive anesthesia in scaling and root during periodontal therapy||The sample size calculation was based on pain intensity (primary outcome) using visual analogue scale (VAS) data. The study reported no difference between intervention groups concerning pain frequency/intensity (primary outcome). The anesthetic gel did not interfere with the hemodynamic parameters (secondary outcome). However, the above observations have a few limitations: First, there is no ideal scale for measuring pain and hence further clarification is necessary. Second, periodontal procedures usually cause low or moderate pain. Third, there was low patient compliance as many did not prefer local anesthesia.|||
|Gel||Doxycycline encapsulated in β-cyclodextrin||Periodontitis||A randomized, blinded clinical trial to compare the effects of 10% doxycycline gel with doxycycline encapsulated in β-cyclodextrin gel on 33 subjects with periodontitis for 30 days.||The adjunctive topical agents (doxycycline encapsulated in β-cyclodextrin gel) along with scaling and root planning resulted in significant improvements in clinical periodontal parameters such as visible plaque index, measurement of periodontal probing depth, clinical attachment level, and bleeding on probing.|||
|Hybrid hydrogels||Mesoporous silica, minocycline, silver, and gelatin methacrylate||Periodontal infection||Near-infrared light (NIR)-activated hybrid hydrogels||The hybrid hydrogels showed controllable minocycline delivery with increased release rates (in-vitro). The hydrogels also exhibited synergistic antibacterial activity (90%) against Porphyromonas gingivalis. The photothermal treatment was as high as 66.7% against P. gingivalis as well to rapidly eliminate and maintain low bacterial retention in the periodontal pockets. Furthermore, the in-vitro cytotoxicity studies revealed an 80% cell viability.|||
|Hydrogel nanoparticles||Minocycline, zinc oxide, and serum albumin||Periodontitis||Broad-spectrum hydrogel-based minocycline and zinc oxide-loaded serum albumin nanoparticles for periodontitis application with low toxicity and high antimicrobial and antibacterial activity||In in-vitro analysis, a slow-release time was observed. Encapsulation efficiency was 99.99%. The in-vitro skin adhesion experiment showed a bioadhesive force of 0.35 N. Broad-spectrum antimicrobial and antibacterial ability and high cell survival rates with low toxicity were observed.|||
|Microspheres||PLGA, PIC, doxycycline, and lipoxin||Periodontal infection||A tunable and injectable localized system based on PLGA microspheres, containing doxycycline and lipoxin, dispersed into thermo-reversible PIC hydrogel for personalized periodontal application||The in-vitro efficacy and bioactivity of the released doxycycline
had presented a comparable zone of inhibition with respect to fresh or unbound drugs against gram-negative anaerobic bacteria Porphyromonas gingivalis (ATCC 33277). The fluorescent bead internalization assay of lipoxin revealed that more fluorescent beads were internalized that may stimulate RAW264.7 macrophage (Gibco) phagocytosis. The in-vivo test on ten 8-week-old male Wistar rats (~250 g) had exhibited no obvious inflammatory responses.
|Combination gel||Chlorhexidine and metronidazole||Gingivitis||A triple-blind randomized clinical trial on 90 subjects to compare and assess 0.8% metronidazole gel, 0.2% chlorhexidine gel, and the alternate application of the two gels against dental plaque and gingivitis for 14 days||The primary outcome measures are the bleeding index. The secondary outcome measures are the oral hygiene index, probing depth, and gingival index. The aforementioned outcomes were compared after 2 and 6 weeks.|||
|Chitosan templates||Chitosan, glutaraldehyde, and doxycycline hyclate||Periodontal tissue regeneration||Cross-linking doxycycline-loaded freeze gelated chitosan templates for periodontitis||The in-vitro analysis of chitosan templates through a conventional dialysis sac method showed a 40 μg/mL of release after 24 h. Such a suitable drug release rate will also limit the toxicological effect of the cross-linking agent.|||
|Retraction gels||Epinephrine, tetrahydrozoline, oxymetazoline, and phenylephrine||Gingival retraction||In-vitro vaso-constrictive retraction agents against primary human gingival fibroblasts in periodontal tissues||Immunocytochemical analysis revealed the biological effect of retraction gels on the expression of collagen types I and III. The generation of the reactive oxygen species triggered by the retraction gels indicated oxidative stress similar to the control cells using the dichlorofluorescein (DCF) fluorescent probe.|||
|In-situ gel||Doxycycline hyclate, shellac, ethocel, and eudragit RS||Periodontitis||In-situ forming gels for localized periodontal pocket delivery.||The in-vitro release study through a dialysis membrane follows a sustained release pattern. It also exhibited in-vitro degradability and the antimicrobial effect against S. aureus, S mutans, E. coli, P. gingivalis, and C. albicans.|||
|Nanofiber based hydrogel||Cellulose, κ-carrageenan oligosaccharide, surfactin, and herbmedotcin||Periodontitis||Anti-microbial loaded cellulose nanofiber and κ-carrageenan oligosaccharide composite hydrogels for strong antibacterial activity against periodontal pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum, and Pseudomonas aeruginosa in periodontitis treatment||Purportedly, they reduce the reactive oxygen species (ROS) generation, transcription factor, and cytokine production in human gingival fibroblast cells (HGF) under inflammatory conditions.|||
|Hydrosilver gel||Silver||Chronic periodontitis||A prospective longitudinal pilot study using polymerase chain reaction analysis of hydrosilver gel against dental plaque in chronic periodontitis||The in-vivo model of chronic periodontitis was used for 15 days. The LAB®-test (LAB s.r.l.®, Ferrara, Italy) detected and quantified the presence and level of the most involved periodontitis pathogens that constitute the ‘red complex’: P. gingivalis, Tannerella forsythia and Treponema denticola. Other bacteria of the ‘orange complex’ were also monitored, such as Fusobacterium nucleatum, Campylobacter rectus, Aggregatibacter actinomycetemcomitans, Atopobium rimae, Eubacterium saphenum, Porphyromonas endodontalis, and Treponema lecithinolyticum, as the main components of microbiological shift.|||
|Microporous annealed particle (MAP) hydrogels||Poly(ethylene) glycol||Tissue engineering and regeneration||Versatile new platform for the delivery of human periodontal ligament stem cells and periodontal tissue regeneration||In-vitro characterization revealed excellent retention, proliferation, and spreading of platelet-derived growth factors and human periodontal ligament stem cells within hydrogels.|||
|Exosomal nanoparticles||Ginger phosphatidic acid||Oral biofilms||Plant-derived nanoparticles to inhibit P. gingivalis biofilm||Demonstrated inhibition of P. gingivalis induced bone loss and pathogenicity in an in-vivo mouse model of chronic periodontitis|||
|Mesoporous nanospheres||Ipriflavone||Periodontal infection||Ipriflavone-loaded mesoporous nanospheres for periodontal augmentation||Periodontal augmentation was observed in an in-vitro osteogenesis model (MC3T3-E1 osteoprogenitor cells).|||
|Nanocomposites||Chlorin e6||Periodontal diseases||A photodynamic therapy-guided bioactive nanocomposite containing chlorin e6 as a photosensitizer against biofilms on dentin squares. The dentin samples were prepared from extracted caries-free human molars that serve as the substrates for biofilm formation.||Photosensitizer effect on Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum and their corresponding biofilms on dentin squares 5 × 5 mm (thickness of about 1 mm).|||
|Nanocomplexes||Bovine serum albumin||Periodontitis||Nanocomplexes for enhanced osteogenic differentiation of inflammatory periodontal ligament stem cells||The in-vitro hemolysis assay and in-vivo cytocompatibility assay using BALB/c mice (8 weeks old) revealed the high transfection efficiency and biocompatibility of the prepared nano complexes.|||
|Carbon quantum dots||Tinidazole and metronidazole||Oral biofilms||Periodontitis treatment by penetrating the P. gingivalis biofilm and destroying its related genes||An in-vitro biofilm penetration assay revealed that nanoscale tinidazole carbon quantum dots can penetrate through the biofilm to induce significant inhibition of P. gingivalis under the biofilm. In addition, as exhibited in the in-vitro antibacterial assay, tinidazole carbon quantum dots impair toxicity and inhibit the major virulence factors and related genes involved in the biofilm formation of P. gingivalis.|||
|Nanoplatelets||Fluoride||Periodontal bone tissue regeneration||Osteogenic differentiation of human dental follicle stem cells for tissue regeneration||MTS assay and cellular morphology analysis demonstrated low cytotoxicity of prepared nanoplatelets at low concentrations.|||
The entry is from 10.3390/pharmaceutics13081175
- Divaris, K. Searching Deep and Wide: Advances in the Molecular Understanding of Dental Caries and Periodontal Disease. Adv. Dent. Res. 2019, 30, 40–44.
- Jain, P.; Mirza, M.A.; Iqbal, Z. Unraveling the Etiology of Periodontitis. Int. J. Biomed. Investig. 2021, 4, 1–4.
- Jain, P.; Mirza, M.A.; Iqbal, Z. A 4-D Approach for Amelioration of Periodontitis. Med. Hypotheses 2019, 133, 109392.
- Bui, F.Q.; Almeida-da-Silva, C.L.C.; Huynh, B.; Trinh, A.; Liu, J.; Woodward, J.; Asadi, H.; Ojcius, D.M. Association between Periodontal Pathogens and Systemic Disease. Biomed. J. 2019, 42, 27–35.
- Falcao, A.; Bullón, P. A Review of the Influence of Periodontal Treatment in Systemic Diseases. Periodontology 2019, 79, 117–128.
- Abusleme, L.; Dupuy, A.K.; Dutzan, N.; Silva, N.; Burleson, J.A.; Strausbaugh, L.D.; Gamonal, J.; Diaz, P.I. The Subgingival Microbiome in Health and Periodontitis and Its Relationship with Community Biomass and Inflammation. ISME J. 2013, 7, 1016–1025.
- Fox, S.; Leitch, A.E.; Duffin, R.; Haslett, C.; Rossi, A.G. Neutrophil Apoptosis: Relevance to the Innate Immune Response and Inflammatory Disease. J. Innate Immun. 2010, 2, 216–227.
- Paul, O.; Arora, P.; Mayer, M.; Chatterjee, S. Inflammation in Periodontal Disease: Possible Link to Vascular Disease. Front. Physiol. 2021, 11, 1818.
- Cecoro, G.; Annunziata, M.; Iuorio, M.T.; Nastri, L.; Guida, L. Periodontitis, Low-Grade Inflammation and Systemic Health: A Scoping Review. Medicina 2020, 56, 272.
- Hajishengallis, G.; Chavakis, T. Local and Systemic Mechanisms Linking Periodontal Disease and Inflammatory Comorbidities. Nat. Rev. Immunol. 2021, 21, 1–15.
- Preshaw, P.M.; Taylor, J.J.; Jaedicke, K.M.; de Jager, M.; Bikker, J.W.; Selten, W.; Bissett, S.M.; Whall, K.M.; van de Merwe, R.; Areibi, A. Treatment of Periodontitis Reduces Systemic Inflammation in Type 2 Diabetes. J. Clin. Periodontol. 2020, 47, 737–746.
- Rapone, B.; Ferrara, E.; Corsalini, M.; Qorri, E.; Converti, I.; Lorusso, F.; Delvecchio, M.; Gnoni, A.; Scacco, S.; Scarano, A. Inflammatory Status and Glycemic Control Level of Patients with Type 2 Diabetes and Periodontitis: A Randomized Clinical Trial. Int. J. Environ. Res. Public Health 2021, 18, 3018.
- Igari, K.; Kudo, T.; Toyofuku, T.; Inoue, Y.; Iwai, T. Association between Periodontitis and the Development of Systemic Diseases. Oral Biol. Dent. 2014, 2, 4.
- Tonetti, M.S.; Van Dyke, T.E.; Working Group 1 of the Joint EFP/AAP Workshop. Periodontitis and Atherosclerotic Cardiovascular Disease: Consensus Report of the Joint EFP/AAPWorkshop on Periodontitis and Systemic Diseases. J. Periodontol. 2013, 84, S24–S29.
- Blaizot, A.; Vergnes, J.-N.; Nuwwareh, S.; Amar, J.; Sixou, M. Periodontal Diseases and Cardiovascular Events: Meta-Analysis of Observational Studies. Int. Dent. J. 2009, 59, 197–209.
- Janket, S.-J.; Baird, A.E.; Chuang, S.-K.; Jones, J.A. Meta-Analysis of Periodontal Disease and Risk of Coronary Heart Disease and Stroke. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontol. 2003, 95, 559–569.
- Bäck, M.; Yurdagul, A.; Tabas, I.; Öörni, K.; Kovanen, P.T. Inflammation and Its Resolution in Atherosclerosis: Mediators and Therapeutic Opportunities. Nat. Rev. Cardiol. 2019, 16, 389–406.
- Sanz, M.; Marco del Castillo, A.; Jepsen, S.; Gonzalez-Juanatey, J.R.; D’Aiuto, F.; Bouchard, P.; Chapple, I.; Dietrich, T.; Gotsman, I.; Graziani, F. Periodontitis and Cardiovascular Diseases: Consensus Report. J. Clin. Periodontol. 2020, 47, 268–288.
- Jiménez-Sánchez, M.C.; Cabanillas-Balsera, D.; Areal-Quecuty, V.; Velasco-Ortega, E.; Martín-González, J.; Segura-Egea, J.J. Cardiovascular Diseases and Apical Periodontitis: Association Not Always Implies Causality. Med. Oral Patol. Oral Cir. Bucal 2020, 25, e652.
- Miricescu, D.; Totan, A.; Stanescu, I.-I.; Radulescu, R.; Stefani, C.; Alexandra Stanescu, A.M.; Greabu, M. Periodontal disease and systemic health. Rom. Med. J. 2019, 66, 197–201.
- Zardawi, F.; Gul, S.; Abdulkareem, A.; Sha, A.; Yates, J. Association between Periodontal Disease and Atherosclerotic Cardiovascular Diseases: Revisited. Front. Cardiovasc. Med. 2020, 7, 625579.
- Bourgeois, D.; Inquimbert, C.; Ottolenghi, L.; Carrouel, F. Periodontal Pathogens as Risk Factors of Cardiovascular Diseases, Diabetes, Rheumatoid Arthritis, Cancer, and Chronic Obstructive Pulmonary Disease—Is There Cause for Consideration? Microorganisms 2019, 7, 424.
- Ji, S.; Choi, Y. Microbial and Host Factors That Affect Bacterial Invasion of the Gingiva. J. Dent. Res. 2020, 99, 1013–1020.
- Yamamoto, T.; Eguchi, T. Heat Shock Proteins and Periodontitis–Cross-Reaction Between Bacterial and Human HSP in Periodontal Infection Linking with Cardiovascular Diseases. In Heat Shock Proteins; Springer: Dordrecht, The Netherlands, 2020.
- Esteves-Lima, R.-P.; Reis, C.-S.; Santirocchi-Júnior, F.; Abreu, L.-G.; Costa, F.-O. Association between Periodontitis and Serum C-Reactive Protein Levels. J. Clin. Exp. Dent. 2020, 12, e838.
- Montero, E.; López, M.; Vidal, H.; Martínez, M.; Virto, L.; Marrero, J.; Herrera, D.; Zapatero, A.; Sanz, M. Impact of Periodontal Therapy on Systemic Markers of Inflammation in Patients with Metabolic Syndrome: A Randomized Clinical Trial. Diabetes Obes. Metab. 2020, 22, 2120–2132.
- Degasperi, G.R.; Ossick, M.V.; Pinheiro, S.L.; Etchegaray, A. Autoimmunity and Periodontal Disease: Arguing a Possible Correlation. Indian J. Dent. Res. 2020, 31, 615.
- Möller, B.; Kollert, F.; Sculean, A.; Villiger, P.M. Infectious Triggers in Periodontitis and the Gut in Rheumatoid Arthritis (RA): A Complex Story about Association and Causality. Front. Immunol. 2020, 11, 1108.
- Ballini, A.; Dipalma, G.; Isacco, C.G.; Boccellino, M.; Di Domenico, M.; Santacroce, L.; Nguyễn, K.C.; Scacco, S.; Calvani, M.; Boddi, A. Oral Microbiota and Immune System Crosstalk: A Translational Research. Biology 2020, 9, 131.
- Lamont, R.J.; Hajishengallis, G.N.; Koo, H.M.; Jenkinson, H.F. Oral Microbiology and Immunology; John Wiley & Sons: Hoboken, NJ, USA, 2020.
- Xu, W.; Zhou, W.; Wang, H.; Liang, S. Roles of Porphyromonas Gingivalis and Its Virulence Factors in Periodontitis. Adv. Protein Chem. Struct. Biol. 2020, 120, 45–84.
- Chopra, A.; Bhat, S.G.; Sivaraman, K. Porphyromonas Gingivalis Adopts Intricate and Unique Molecular Mechanisms to Survive and Persist within the Host: A Critical Update. J. Oral Microbiol. 2020, 12, 1801090.
- Hočevar, K.; Vizovišek, M.; Wong, A.; Koziel, J.; Fonović, M.; Potempa, B.; Lamont, R.J.; Potempa, J.; Turk, B. Proteolysis of Gingival Keratinocyte Cell Surface Proteins by Gingipains Secreted From Porphyromonas Gingivalis–Proteomic Insights Into Mechanisms Behind Tissue Damage in the Diseased Gingiva. Front. Microbiol. 2020, 11, 722.
- Farrugia, C.; Stafford, G.P.; Potempa, J.; Wilkinson, R.N.; Chen, Y.; Murdoch, C.; Widziolek, M. Mechanisms of Vascular Damage by Systemic Dissemination of the Oral Pathogen Porphyromonas Gingivalis. FEBS J. 2021, 288, 1479–1495.
- Sapey, E.; Onel, Z.; Edgar, R.; Parmar, S.; Hobbins, S.; Newby, P.; Crossley, D.; Usher, A.; Johnson, S.; Walton, G.M. The Clinical and Inflammatory Relationships between Periodontitis and Chronic Obstructive Pulmonary Disease. J. Clin. Periodontol. 2020, 47, 1040–1052.
- Gomes-Filho, I.S.; da Cruz, S.S.; Trindade, S.C.; Passos-Soares, J.d.S.; Carvalho-Filho, P.C.; Figueiredo, A.C.M.G.; Lyrio, A.O.; Hintz, A.M.; Pereira, M.G.; Scannapieco, F. Periodontitis and Respiratory Diseases: A Systematic Review with Meta-Analysis. Oral Dis. 2020, 26, 439–446.
- Shehri, I.; Nissar, S.; Anis, B.A.; Singh, S. Evaluation of Prevalence of Periodontitis in Patients with Pulmonary Disease. J. Adv. Med. Dent. Sci. Res. 2020, 8, 72–75.
- Apessos, I.; Voulgaris, A.; Agrafiotis, M.; Andreadis, D.; Steiropoulos, P. Effect of Periodontal Therapy on COPD Outcomes: A Systematic Review. BMC Pulm. Med. 2021, 21, 1–16.
- Genco, R.J.; Graziani, F.; Hasturk, H. Effects of Periodontal Disease on Glycemic Control, Complications, and Incidence of Diabetes Mellitus. Periodontology 2020, 83, 59–65.
- Nguyen, A.T.M.; Akhter, R.; Garde, S.; Scott, C.; Twigg, S.M.; Colagiuri, S.; Ajwani, S.; Eberhard, J. The Association of Periodontal Disease with the Complications of Diabetes Mellitus. A Systematic Review. Diabetes Res. Clin. Pract. 2020, 165, 108244.
- Graves, D.T.; Ding, Z.; Yang, Y. The Impact of Diabetes on Periodontal Diseases. Periodontology 2020, 82, 214–224.
- AlQranei, M.S.; Chellaiah, M.A. Osteoclastogenesis in Periodontal Diseases: Possible Mediators and Mechanisms. J. Oral Biosci. 2020, 62, 123–130.
- Polak, D.; Sanui, T.; Nishimura, F.; Shapira, L. Diabetes as a Risk Factor for Periodontal Disease—Plausible Mechanisms. Periodontology 2020, 83, 46–58.
- Pérez-Losada, F.D.L.; Estrugo-Devesa, A.; Castellanos-Cosano, L.; Segura-Egea, J.J.; López-López, J.; Velasco-Ortega, E. Apical Periodontitis and Diabetes Mellitus Type 2: A Systematic Review and Meta-Analysis. J. Clin. Med. 2020, 9, 540.
- Wu, C.; Yuan, Y.; Liu, H.; Li, S.; Zhang, B.; Chen, W.; An, Z.; Chen, S.; Wu, Y.; Han, B.; et al. Epidemiologic Relationship between Periodontitis and Type 2 Diabetes Mellitus. BMC Oral Health 2020, 20, 204.
- Jinnat, M.A.; Ahmed, S.; Monira, S.; Haque, M.M.; Musharraf, M.; Hasan, M.R. Maternal Risk Factors, Clinical Profile and Short-Term Outcome of Pre-Term Low Birth Weight Babies. KYAMC J. 2020, 11, 77–82.
- Green, E.S.; Arck, P.C. Pathogenesis of Preterm Birth: Bidirectional Inflammation in Mother and Fetus. Semin. Immunopathol. 2020, 42, 413–429.
- Parris, K.M.; Amabebe, E.; Cohen, M.C.; Anumba, D.O. Placental Microbial–Metabolite Profiles and Inflammatory Mechanisms Associated with Preterm Birth. J. Clin. Pathol. 2021, 74, 10–18.
- Boggess, K.A. Choosing the Left Fork: Steven Offenbacher and Understanding Maternal Periodontal Disease and Adverse Pregnancy Outcomes. J. Periodontol. 2020, 91, S40–S44.
- Manrique-Corredor, E.J.; Orozco-Beltran, D.; Lopez-Pineda, A.; Quesada, J.A.; Gil-Guillen, V.F.; Carratala-Munuera, C. Maternal Periodontitis and Preterm Birth: Systematic Review and Meta-analysis. Community Dent. Oral Epidemiol. 2019, 47, 243–251.
- Madianos, P.; Lieff, S.; Murtha, A.; Boggess, K.; Auten, R., Jr.; Beck, J.; Offenbacher, S. Maternal Periodontitis and Prematurity. Part II: Maternal Infection and Fetal Exposure. Ann. Periodontol. 2001, 6, 175–182.
- Ferlay, J.; Colombet, M.; Soerjomataram, I.; Parkin, D.M.; Piñeros, M.; Znaor, A.; Bray, F. Cancer Statistics for the Year 2020: An Overview. Int. J. Cancer 2021, 149, 778–789.
- Piotrowski, I.; Kulcenty, K.; Suchorska, W. Interplay between Inflammation and Cancer. Rep. Pract. Oncol. Radiother. 2020, 25, 422–427.
- Irani, S.; Barati, I.; Badiei, M. Periodontitis and Oral Cancer—Current Concepts of the Etiopathogenesis. Oncol. Rev. 2020, 14, 465.
- Chung, P.-C.; Chan, T.-C. Association between Periodontitis and All-Cause and Cancer Mortality: Retrospective Elderly Community Cohort Study. BMC Oral Health 2020, 20, 168.
- Jain, P.; Mirza, M.A.; Talegaonkar, S.; Nandy, S.; Dudeja, M.; Sharma, N.; Anwer, M.K.; Alshahrani, S.M.; Iqbal, Z. Design and in-vitro/in-vivo Evaluations of a Multiple-Drug-Containing Gingiva Disc for Periodontotherapy. RSC Adv. 2020, 10, 8530–8538.
- Abdelaziz, D.; Hefnawy, A.; Al-Wakeel, E.; El-Fallal, A.; El-Sherbiny, I.M. New Biodegradable Nanoparticles-in-Nanofibers Based Membranes for Guided Periodontal Tissue and Bone Regeneration with Enhanced Antibacterial Activity. J. Adv. Res. 2021, 28, 51–62.
- Boda, S.K.; Almoshari, Y.; Wang, H.; Wang, X.; Reinhardt, R.A.; Duan, B.; Wang, D.; Xie, J. Mineralized Nanofiber Segments Coupled with Calcium-Binding BMP-2 Peptides for Alveolar Bone Regeneration. Acta Biomater. 2019, 85, 282–293.
- Mahmoud, M.Y.; Sapare, S.; Curry, K.C.; Demuth, D.R.; Steinbach-Rankins, J.M. Rapid Release Polymeric Fibers for Inhibition of Porphyromonas Gingivalis Adherence to Streptococcus Gordonii. Front. Chem. 2019, 7, 926.
- Liu, X.; He, X.; Jin, D.; Wu, S.; Wang, H.; Yin, M.; Aldalbahi, A.; El-Newehy, M.; Mo, X.; Wu, J. A Biodegradable Multifunctional Nanofibrous Membrane for Periodontal Tissue Regeneration. Acta Biomater. 2020, 108, 207–222.
- Ahi, Z.B.; Renkler, N.Z.; Gul Seker, M.; Tuzlakoglu, K. Biodegradable Polymer Films with a Natural Antibacterial Extract as Novel Periodontal Barrier Membranes. Int. J. Biomater. 2019, 2019, 7932470.
- Chiaoprakobkij, N.; Suwanmajo, T.; Sanchavanakit, N.; Phisalaphong, M. Curcumin-Loaded Bacterial Cellulose/Alginate/Gelatin as A Multifunctional Biopolymer Composite Film. Molecules 2020, 25, 3800.
- Tovar-Carrillo, K.L.; Saucedo-Acuña, R.A.; Ríos-Arana, J.; Tamayo, G.; Guzmán-Gastellum, D.A.; Díaz-Torres, B.A.; Nava-Martínez, S.D.; Espinosa-Cristóbal, L.F.; Cuevas-González, J.C. Synthesis, Characterization, and In-vitro and In-vivo Evaluations of Cellulose Hydrogels Enriched with Larrea Tridentata for Regenerative Applications. BioMed Res. Int. 2020, 2020, 1425402.
- Jain, P.; Garg, A.; Farooq, U.; Panda, A.K.; Mirza, M.A.; Noureldeen, A.; Darwish, H.; Iqbal, Z. Preparation and Quality by Design Assisted (Qb-d) Optimization of Bioceramic Loaded Microspheres for Periodontal Delivery of Doxycycline Hyclate. Saudi J. Biol. Sci. 2021, 28, 2677–2685.
- Lian, M.; Sun, B.; Qiao, Z.; Zhao, K.; Zhou, X.; Zhang, Q.; Zou, D.; He, C.; Zhang, X. Bi-Layered Electrospun Nanofibrous Membrane with Osteogenic and Antibacterial Properties for Guided Bone Regeneration. Colloids Surf. B Biointerfaces 2019, 176, 219–229.
- Jeong, J.-O.; Park, J.-S.; Kim, E.J.; Jeong, S.-I.; Lee, J.Y.; Lim, Y.-M. Preparation of Radiation Cross-Linked Poly(Acrylic Acid) Hydrogel Containing Metronidazole with Enhanced Antibacterial Activity. Int. J. Mol. Sci. 2019, 21, 187.
- Wang, B.; Booij-Vrieling, H.E.; Bronkhorst, E.M.; Shao, J.; Kouwer, P.H.J.; Jansen, J.A.; Walboomers, X.F.; Yang, F. Antimicrobial and Anti-Inflammatory Thermo-Reversible Hydrogel for Periodontal Delivery. Acta Biomater. 2020, 116, 259–267.
- Moraes, G.S.; Santos, I.B.D.; Pinto, S.C.S.; Pochapski, M.T.; Farago, P.V.; Pilatti, G.L.; Santos, F.A. Liposomal Anesthetic Gel for Pain Control during Periodontal Therapy in Adults: A Placebo-Controlled RCT. J. Appl. Oral Sci. Rev. FOB 2020, 28, e20190025.
- Trajano, V.C.D.C.; Brasileiro, C.B.; Henriques, J.A.D.S.; Cota, L.D.M.; Lanza, C.R.; Cortés, M.E. Doxycycline Encapsulated in β-Cyclodextrin for Periodontitis: A Clinical Trial. Braz. Oral Res. 2020, 33, e112.
- Lin, J.; He, Z.; Liu, F.; Feng, J.; Huang, C.; Sun, X.; Deng, H. Hybrid Hydrogels for Synergistic Periodontal Antibacterial Treatment with Sustained Drug Release and NIR-Responsive Photothermal Effect. Int. J. Nanomed. 2020, 15, 5377–5387.
- Mou, J.; Liu, Z.; Liu, J.; Lu, J.; Zhu, W.; Pei, D. Hydrogel Containing Minocycline and Zinc Oxide-Loaded Serum Albumin Nanopartical for Periodontitis Application: Preparation, Characterization and Evaluation. Drug Deliv. 2019, 26, 179–187.
- Wang, B.; Wang, J.; Shao, J.; Kouwer, P.H.J.; Bronkhorst, E.M.; Jansen, J.A.; Walboomers, X.F.; Yang, F. A Tunable and Injectable Local Drug Delivery System for Personalized Periodontal Application. J. Control. Release 2020, 324, 134–145.
- Badar, S.B.; Zafar, K.; Ghafoor, R.; Khan, F.R. Comparative Evaluation of Chlorhexidine, Metronidazole and Combination Gels on Gingivitis: A Randomized Clinical Trial. Int. J. Surg. Protoc. 2019, 14, 30–33.
- Qasim, S.S.B.; Nogueria, L.P.; Fawzy, A.S.; Daood, U. The Effect of Cross-Linking Efficiency of Drug-Loaded Novel Freeze Gelated Chitosan Templates for Periodontal Tissue Regeneration. AAPS PharmSciTech 2020, 21, 173.
- Nowakowska, D.; Saczko, J.; Szewczyk, A.; Michel, O.; Ziętek, M.; Weżgowiec, J.; Więckiewicz, W.; Kulbacka, J. In-vitro Effects of Vasoconstrictive Retraction Agents on Primary Human Gingival Fibroblasts. Exp. Ther. Med. 2020, 19, 2037–2044.
- Senarat, S.; Wai Lwin, W.; Mahadlek, J.; Phaechamud, T. Doxycycline Hyclate-Loaded in-situ Forming Gels Composed from Bleached Shellac, Ethocel, and Eudragit RS for Periodontal Pocket Delivery. Saudi Pharm. J. 2021, 29, 252–263.
- Johnson, A.; Kong, F.; Miao, S.; Lin, H.-T.V.; Thomas, S.; Huang, Y.-C.; Kong, Z.-L. Therapeutic Effects of Antibiotics Loaded Cellulose Nanofiber and κ-Carrageenan Oligosaccharide Composite Hydrogels for Periodontitis Treatment. Sci. Rep. 2020, 10, 18037.
- Lauritano, D.; Nota, A.; Martinelli, M.; Severino, M.; Romano, M.; Rossi, D.; Caruso, S. A Hydrosilver Gel for Plaque Control in Adults Affected by Chronic Periodontitis: Effects on the “red Complex” Bacterial Load. A Prospective Longitudinal Pilot Study Using Polymerase Chain Reaction Analysis. Int. J. Immunopathol. Pharmacol. 2019, 33, 2058738418825212.
- Isaac, A.; Jivan, F.; Xin, S.; Hardin, J.; Luan, X.; Pandya, M.; Diekwisch, T.G.H.; Alge, D.L. Microporous Bio-Orthogonally Annealed Particle Hydrogels for Tissue Engineering and Regenerative Medicine. ACS Biomater. Sci. Eng. 2019, 5, 6395–6404.
- Sundaram, K.; Miller, D.P.; Kumar, A.; Teng, Y.; Sayed, M.; Mu, J.; Lei, C.; Sriwastva, M.K.; Zhang, L.; Yan, J.; et al. Plant-Derived Exosomal Nanoparticles Inhibit Pathogenicity of Porphyromonas Gingivalis. iScience 2020, 23, 100869.
- Casarrubios, L.; Gómez-Cerezo, N.; Feito, M.J.; Vallet-Regí, M.; Arcos, D.; Portolés, M.T. Ipriflavone-Loaded Mesoporous Nanospheres with Potential Applications for Periodontal Treatment. Nanomaterials 2020, 10, 2573.
- Zhang, T.; Ying, D.; Qi, M.; Li, X.; Fu, L.; Sun, X.; Wang, L.; Zhou, Y. Anti-Biofilm Property of Bioactive Upconversion Nanocomposites Containing Chlorin E6 against Periodontal Pathogens. Molecules 2019, 24, 2692.
- Wang, Y.; Song, W.; Cui, Y.; Zhang, Y.; Mei, S.; Wang, Q. Calcium-SiRNA Nanocomplexes Optimized by Bovine Serum Albumin Coating Can Achieve Convenient and Efficient SiRNA Delivery for Periodontitis Therapy. Int. J. Nanomed. 2020, 15, 9241–9253.
- Liang, G.; Shi, H.; Qi, Y.; Li, J.; Jing, A.; Liu, Q.; Feng, W.; Li, G.; Gao, S. Specific Anti-Biofilm Activity of Carbon Quantum Dots by Destroying P. Gingivalis Biofilm Related Genes. Int. J. Nanomed. 2020, 15, 5473–5489.
- Veernala, I.; Giri, J.; Pradhan, A.; Polley, P.; Singh, R.; Yadava, S.K. Effect of Fluoride Doping in Laponite Nanoplatelets on Osteogenic Differentiation of Human Dental Follicle Stem Cells (HDFSCs). Sci. Rep. 2019, 9, 915.
- Golub, L.M.; Lee, H.-M. Periodontal Therapeutics: Current Host-Modulation Agents and Future Directions. Periodontology 2020, 82, 186–204.
- Kim, W.J.; Soh, Y.; Heo, S.-M. Recent Advances of Therapeutic Targets for the Treatment of Periodontal Disease. Biomol. Ther. 2021, 29, 263–267.
- Muras, A.; Mallo, N.; Otero-Casal, P.; Pose-Rodríguez, J.M.; Otero, A. Quorum Sensing Systems as a New Target to Prevent Biofilm-related Oral Diseases. Oral Dis. 2020.
- Marchesan, J.T.; Girnary, M.S.; Moss, K.; Monaghan, E.T.; Egnatz, G.J.; Jiao, Y.; Zhang, S.; Beck, J.; Swanson, K.V. Role of Inflammasomes in the Pathogenesis of Periodontal Disease and Therapeutics. Periodontology 2020, 82, 93–114.
- Qi, M.; Chi, M.; Sun, X.; Xie, X.; Weir, M.D.; Oates, T.W.; Zhou, Y.; Wang, L.; Bai, Y.; Xu, H.H. Novel Nanomaterial-Based Antibacterial Photodynamic Therapies to Combat Oral Bacterial Biofilms and Infectious Diseases. Int. J. Nanomed. 2019, 14, 6937–6956.