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Journal of Nanobiotechnology Jan 2024Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth... (Review)
Review
Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends.
Topics: Humans; Periodontitis; Periodontium; Anti-Bacterial Agents; Regeneration; Immunomodulation; Immunity
PubMed: 38178140
DOI: 10.1186/s12951-023-02261-y -
Bioactive Materials Oct 2021The periodontium is an integrated, functional unit of multiple tissues surrounding and supporting the tooth, including but not limited to cementum (CM), periodontal... (Review)
Review
The periodontium is an integrated, functional unit of multiple tissues surrounding and supporting the tooth, including but not limited to cementum (CM), periodontal ligament (PDL) and alveolar bone (AB). Periodontal tissues can be destructed by chronic periodontal disease, which can lead to tooth loss. In support of the treatment for periodontally diseased tooth, various biomaterials have been applied starting as a contact inhibition membrane in the guided tissue regeneration (GTR) that is the current gold standard in dental clinic. Recently, various biomaterials have been prepared in a form of tissue engineering scaffold to facilitate the regeneration of damaged periodontal tissues. From a physical substrate to support healing of a single type of periodontal tissue to multi-phase/bioactive scaffold system to guide an integrated regeneration of periodontium, technologies for scaffold fabrication have emerged in last years. This review covers the recent advancements in development of scaffolds designed for periodontal tissue regeneration and their efficacy tested and . Pros and Cons of different biomaterials and design parameters implemented for periodontal tissue regeneration are also discussed, including future perspectives.
PubMed: 33817414
DOI: 10.1016/j.bioactmat.2021.03.012 -
Journal of Dental Research Jun 2021Biomineralization is regulated by inorganic pyrophosphate (PP), a potent physiological inhibitor of hydroxyapatite crystal growth. Progressive ankylosis protein (ANK)...
Biomineralization is regulated by inorganic pyrophosphate (PP), a potent physiological inhibitor of hydroxyapatite crystal growth. Progressive ankylosis protein (ANK) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) act to increase local extracellular levels of PP, inhibiting mineralization. The periodontal complex includes 2 mineralized tissues, cementum and alveolar bone (AB), both essential for tooth attachment. Previous studies demonstrated that loss of function of ANK or ENPP1 (reducing PP) resulted in increased cementum formation, suggesting PP metabolism may be a target for periodontal regenerative therapies. To compare the effects of genetic ablation of , and both factors concurrently on cementum and AB regeneration, mandibular fenestration defects were created in knockout ( KO), mutant (), and double KO (dKO) mice. Genetic ablation of , or both factors increased cementum regeneration compared to controls at postoperative days (PODs) 15 and 30 ( KO: 8-fold, 3-fold; : 7-fold, 3-fold; dKO: 11-fold, 4-fold, respectively) associated with increased fluorochrome labeling and expression of mineralized tissue markers, dentin matrix protein 1 (/DMP1), osteopontin (/OPN), and bone sialoprotein (/BSP). Furthermore, dKO mice featured increased cementum thickness compared to single KOs at POD15 and KO at POD30. No differences were noted in AB volume between genotypes, but osteoblast/osteocyte markers were increased in all KOs, partially mineralized osteoid volume was increased in dKO versus controls at POD15 (3-fold), and mineral density was decreased in and dKOs at POD30 (6% and 9%, respectively). Increased numbers of osteoclasts were present in regenerated AB of all KOs versus controls. These preclinical studies suggest PP modulation as a potential and novel approach for cementum regeneration, particularly targeting ENPP1 and/or ANK. Differences in cementum and AB regeneration in response to reduced PP conditions highlight the need to consider tissue-specific responses in strategies targeting regeneration of the entire periodontal complex.
Topics: Animals; Bone and Bones; Dental Cementum; Diphosphates; Mice; Mice, Knockout; Tooth; Tooth Ankylosis
PubMed: 33356859
DOI: 10.1177/0022034520981854 -
Journal of Dental Research Apr 2021Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely... (Review)
Review
Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely critical tasks in responding to a variety of external stimuli and dangers through the regulation of specific built-in molecular mechanisms in a context-dependent fashion at cellular levels. Gingival epithelial cells form an anatomic architecture that confers defense, robustness, and adaptation toward external aggressions, most critically to colonizing microorganisms, among other functions. Accordingly, recent studies unraveled previously uncharacterized response mechanisms in gingival epithelial cells that are constructed to rapidly exert biocidal effects against invader pathobiotic bacteria, such as , through small danger molecule signaling. The host-adapted bacteria, however, have developed adroit strategies to 1) exploit the epithelia as privileged growth niches and 2) chronically target cellular bactericidal and homeostatic metabolic pathways for successful bacterial persistence. As the overgrowth of colonizing microorganisms in the gingival mucosa can shift from homeostasis to dysbiosis or a diseased state, it is crucial to understand how the innate modulatory molecules are intricately involved in antibacterial pathways and how they shape susceptibility versus resistance in the epithelium toward pathogens. Thus, in this review, we highlight recent discoveries in gingival epithelial cell research in the context of bacterial colonizers. The current knowledge outlined here demonstrates the ability of epithelial cells to possess highly organized defense machineries, which can jointly regulate host-derived danger molecule signaling and integrate specific global responses against opportunistic bacteria to combat microbial incursion and maintain host homeostatic balance. These novel examples collectively suggest that the oral epithelia are equipped with a dynamically robust and interconnected defense system encompassing sensors and various effector molecules that arrange and achieve a fine-tuned and advanced response to diverse bacteria.
Topics: Epithelial Cells; Gingiva; Homeostasis; Mouth Mucosa; Porphyromonas gingivalis
PubMed: 33203318
DOI: 10.1177/0022034520973012 -
Brazilian Oral Research 2023Protease-activated receptor-2 (PAR2) is associated with the pathogenesis of many chronic diseases with inflammatory characteristics, including periodontitis. This study...
Protease-activated receptor-2 (PAR2) is associated with the pathogenesis of many chronic diseases with inflammatory characteristics, including periodontitis. This study aimed to evaluate how the activation of PAR2 can affect the osteogenic activity of human periodontal ligament stem cells (PDLSCs) in vitro. PDLSCs collected from three subjects were treated in osteogenic medium for 2, 7, 14, and 21 days with trypsin (0.1 U/mL), PAR2 specific agonist peptide (SLIGRL-NH2) (100 nM), and PAR2 antagonist peptide (FSLLRY-NH2) (100 nM). Gene (RT-qPCR) expression and protein expression (ELISA) of osteogenic factors, bone metabolism, and inflammatory cytokines, cell proliferation, alkaline phosphatase (ALP) activity, alizarin red S staining, and supernatant concentration were assessed. Statistical analysis of the results with a significance level of 5% was performed. Activation of PAR2 led to decreases in cell proliferation and calcium deposition (p < 0.05), calcium concentration (p < 0.05), and ALP activity (p < 0.05). Additionally, PAR2 activation increased gene and protein expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) (p < 0.05) and significantly decreased the gene and protein expression of osteoprotegerin (p <0. 05). Considering the findings, the present study demonstrated PAR2 activation was able to decrease cell proliferation, decreased osteogenic activity of PDLSCs, and upregulated conditions for bone resorption. PAR2 may be considered a promising target in periodontal regenerative procedures.
Topics: Humans; Osteogenesis; Cell Differentiation; Periodontal Ligament; Receptor, PAR-2; Calcium; Stem Cells; Cell Proliferation; Cells, Cultured
PubMed: 36629588
DOI: 10.1590/1807-3107bor-2023.vol37.0002 -
International Journal of Molecular... Oct 2020The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease... (Review)
Review
The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease etiology. DNA damage-driven senescence is perhaps one of the most underappreciated delayed consequences of persistent Gram-negative bacterial infection and inflammation. Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. What happens to those healthy cells that reside in this harmful environment? Emerging evidence indicates that cells that survive irreparable genomic damage undergo cellular senescence, a crucial intermediate mechanism connecting DNA damage and the immune response. In this review, we hypothesize that sustained Gram-negative bacterial challenge, chronic inflammation itself, and the constant renewal of damaged tissues create a permissive environment for the abnormal accumulation of senescent cells. Based on emerging data we propose a model in which the dysfunctional presence of senescent cells may aggravate the initial immune reaction against pathogens. Further understanding of the role of senescent cells in periodontal disease pathogenesis may have clinical implications by providing more sophisticated therapeutic strategies to combat tissue destruction.
Topics: Bacterial Infections; Cellular Microenvironment; Cellular Senescence; DNA Damage; Disease Management; Disease Susceptibility; Host-Pathogen Interactions; Humans; Inflammation; NF-kappa B; Oral Health; Periodontal Diseases; Periodontium; Signal Transduction; Stress, Physiological
PubMed: 33050175
DOI: 10.3390/ijms21207441 -
Frontiers in Veterinary Science 2023Pituitary pars intermedia dysfunction (PPID) and dental disorders are of major concern in horses older than 15 years. Although PPID in geriatric horses and dental...
INTRODUCTION
Pituitary pars intermedia dysfunction (PPID) and dental disorders are of major concern in horses older than 15 years. Although PPID in geriatric horses and dental disorders in all age groups are well described, a connection between this endocrine disease and pathological changes in equine dental structures has not yet been investigated. In humans, periodontitis is considered to be a complication of systemic diseases like diabetes mellitus type 2, obesity and various conditions leading to an impaired immune response. In PPID, cross links to insulin and immune dysregulations are proven. The aim of this study was to compare histological findings of the gingiva and the sub gingival periodontal ligament of PPID affected horses with control horses.
METHODS
In a case-control morphometric descriptive study, 145 dental locations of 10 PPID affected horses (27.3 ± 2.06 years) were compared with 147 dental locations of 10 controls (21.4 ± 4.12 years). Histological parameters were leukocyte infiltration, keratinization of gingival epithelium, blood vessel supply of the periodontium and structure of cementum.
RESULTS
The distribution and localization of gingival leukocyte infiltrations (LI) in PPID affected horses was more often multifocal to coalescing ( = 0.002) and reached into deeper parts of the periodontium, sometimes down to the sub gingival periodontal ligament (PDL). Aged animals of both groups showed higher prevalence (PPID: OR 1.66; controls: OR 1.15) for severe leukocyte infiltration in the PDL. PPID was not significantly associated with increased LI. The cementum bordering the soft tissue in interdental locations showed four times more irregularities in PPID affected horses than in controls which predisposes for interdental food impaction and periodontal diseases.
DISCUSSION
In summary, multifocal to coalescing leukocytes and irregular cementum are seen more often in PPID than in controls - however our findings mainly reflect an association of older age with periodontal disease.
PubMed: 36733635
DOI: 10.3389/fvets.2023.1114445 -
Medical Science Monitor : International... Jan 2022BACKGROUND This study aimed to compare the effectiveness of subgingival scaling and root planing with the Twinlight laser, Er: YAG laser, and hand instrumentation on the...
BACKGROUND This study aimed to compare the effectiveness of subgingival scaling and root planing with the Twinlight laser, Er: YAG laser, and hand instrumentation on the removal of endotoxin and attachment of human gingival fibroblasts (HGFs) to cementum surfaces in vitro. MATERIAL AND METHODS Single-rooted teeth extracted for periodontal disease were collected and divided into 3 groups: group A, root planing with Gracey curet no. 5/6; group B, irradiation with Er: YAG laser; group C, irradiation with Er: YAG laser and Nd: YAG laser. Endotoxins were determined by the limulus amebocyte lysate test. Cell attachment and proliferation of HGFs on root specimens were evaluated by cell counting kit-8 assay. The root surface and cell morphology were observed by scanning electron microscope. RESULTS A flat root surface with scratches was found in group A, Group B had a homogeneous rough morphology without carbonization, and group C had a non-homogeneous rough morphology with ablation. The endotoxin concentration was highest in group A (P<0.05) and lowest in group C (P>0.05). HGFs cultured in group B showed significantly increased adhesion and proliferation compared with groups A and C (P<0.05). HGFs in group B were well attached, covered densely by pseudopodia. HGFs in group A were round with poor extension and short pseudopodia, while the cells in the group C were in narrow, triangular, or polygonal shapes. CONCLUSIONS Twinlight laser-assisted periodontal treatment effectively improved the biocompatibility of root surface and promoted the attachment and proliferation of fibroblasts by removing calculus and reducing the concentration of endotoxins.
Topics: Cell Adhesion; Fibroblasts; Gingiva; Humans; Laser Therapy; Lasers, Solid-State; Microscopy, Electron, Scanning; Periodontal Diseases; Root Planing; Surface Properties
PubMed: 34983919
DOI: 10.12659/MSM.932191 -
International Journal of Molecular... May 2021Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral...
Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral microbiome in periodontitis in relation to disease severity and systemic inflammation. The saliva and subgingival microbiome from periodontal pocket samples of patients with severe (n = 12) and mild periodontitis (n = 13) were analyzed using metagenomic shotgun sequencing. The taxa and pathways abundances were quantified. The diversity was assessed and the abundances to phenotype associations were performed using ANCOM and linear regression. A panel of inflammatory markers was measured in blood and was associated with taxa abundance. The microbial diversity and species richness did not differ between severe and mild periodontitis in either saliva or periodontal pockets. However, there were significant differences in the microbial composition between severe and mild periodontitis in the subgingival microbiome (i.e., pocket samples) and, in a lower grade, in saliva, and this is positively associated with systemic inflammatory markers. The "red complex" and "cluster B" abundances in periodontal pockets were strongly associated with inflammatory markers interleukin-6 and the white blood cell count. Our data suggest that systemic inflammation in severe periodontitis may be driven by the oral microbiome and may support the indirect (inflammatory) mechanism for the association between periodontitis and cardiovascular disease.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Female; Gene Expression; Genetic Variation; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Leukocytes; Male; Metagenome; Microbiota; Middle Aged; Periodontitis; Periodontium; Phenotype; Phylogeny; Severity of Illness Index
PubMed: 34070915
DOI: 10.3390/ijms22115876 -
Periodontology 2000 Oct 2022According to the new classification, periodontitis is defined as a chronic multifactorial inflammatory disease associated with dysbiotic biofilms and characterized by... (Review)
Review
According to the new classification, periodontitis is defined as a chronic multifactorial inflammatory disease associated with dysbiotic biofilms and characterized by progressive destruction of the tooth-supporting apparatus. This definition, based on the current scientific evidence, clearly indicates and emphasizes, beside the microbial component dental biofilm, the importance of the inflammatory reaction in the progressive destruction of periodontal tissues. The idea to modulate this inflammatory reaction in order to decrease or even cease the progressive destruction was, therefore, a logical consequence. Attempts to achieve this goal involve various kinds of anti-inflammatory drugs or medications. However, there is also an increasing effort in using food supplements or so-called natural food ingredients to modulate patients' immune responses and maybe even improve the healing of periodontal tissues. The aim of this chapter of Periodontology 2000 is to review the evidence of various food supplements and ingredients regarding their possible effects on periodontal inflammation and wound healing. This review may help researchers and clinicians to evaluate the current evidence and to stimulate further research in this area.
Topics: Dietary Supplements; Food Ingredients; Humans; Inflammation; Life Style; Periodontitis; Periodontium
PubMed: 35916868
DOI: 10.1111/prd.12455