Periodontal Tissue Destruction Research Articles

H2S-Scavenging Hydrogel Alleviating Mitochondria Damage to Control Periodontitis.

H2S, as a typical metabolite of periodontal pathogens, exhibits a clear positive correlation with the occurrence and development of periodontitis. H2S at physiological concentrations can regulate many biological processes. However, excess H2S in the periodontal pocket can trigger secretion of proinflammatory cytokines, cause oxidative stress, and result in mitochondrial damage and cell death in human gingival fibroblasts, exacerbating periodontitis development and periodontal tissue destruction. Worse, H2S facilitates bacteria survival and proliferation by maintaining bacterial redox balance and enhancing antibiotic resistance. Unfortunately, scavenging H2S during periodontitis treatment is usually ignored. Herein, a kind of hyaluronic acid methacryloyl/ZnO (HMZ) composite hydrogel with an H2S-scavenging ability was prepared to enhance periodontitis treatment. The HMZ hydrogel possessed good injectability and cytocompatibility and was able to remove H2S by a reaction with ZnO. As a result, the HMZ hydrogel was able to increase cell viability from 13% to 120% for human gingival fibroblasts and 22% to 94% for human periodontal ligament fibroblasts at 48 h, restore mitochondrial homeostasis, and alleviate cGAS-STING signaling pathway-mediated inflammation. Meanwhile, the HMZ hydrogel showed satisfactory antibacterial properties and efficiency of plaque biofilm removal. The in vivo results further confirmed that HMZ hydrogel decreased the concentration of H2S within the periodontal pocket from 0.7 to 0.8 mM to the normal level (0.3 to 0.4 mM), killed the bacteria in the periodontal tissues, inhibited osteoclast activity, relieved excess inflammation, and decreased the vertical distance between the cementoenamel junction and the alveolar bone crest from 1,175 µm to 798 µm on the 7th day and from 1,075 µm to 693 µm on the 14th day, achieving efficient periodontal bone regeneration. In brief, an H2S scavenging-based promising strategy was developed to enhance the therapeutic efficiency of periodontitis.

An Immunomodulatory Hydrogel Featuring Antibacterial and Reactive Oxygen Species Scavenging Properties for Treating Periodontitis in Diabetes.

Periodontal disease is a multifactorial, bacterially induced inflammatory disorder characterized by progressive destruction of periodontal tissues. Additionally, diabetes mellitus exacerbates periodontitis, resulting in expedited resorption of periodontal bone. However, methods such as mechanical debridement, anti-inflammatory medications, and surgical approaches often fail to eradicate local infections and inflammation, complicating the reconstruction of periodontal tissue structures. Consequently, there is an urgent need to devise a novel strategy for managing diabetic periodontal conditions. Here, a multifunctional controlled-release drug delivery system (GOE1) is developed by encapsulating self-assembled nanoparticles (consisting of chlorhexidine acetate and epigallocatechin-3-gallate) into a hydrogel matrix composed of gelatin methacryloyl and oxidized hyaluronic acid. In vitro experiments demonstrate that the GOE1 hydrogel possesses good antimicrobial, antioxidant and anti-inflammatory properties, and transgenic sequence genomics further illustrates that IL-17-producing RAW 264.7 macrophages are critical for mediating M1/M2 macrophage transition and provide favorable immune microenvironment. In addition, in vivo experiments reveal that GOE1 significantly ameliorates periodontal tissue inflammation and reduces the loss of alveolar bone by reducing inflammatory infiltration and collagen destruction. Overall, the GOE1 hydrogel offers a promising therapeutic option for managing diabetic periodontitis.

The role of interleukin-20 on inflammatory stress and periodontal tissue destruction in patients with metabolic syndrome and periodontitis

BackgroundThere is an increasing occurrence of periodontitis and metabolic syndrome (MetS), which is resulting in a decline in the overall quality of life. Both disorders can occur together since they are both linked to insulin resistance and systemic inflammation. However, evidence for a role of interleukin (IL)-20 in this comorbidity is very limited. This cross-sectional study aimed to comprehensively investigate, for the first time, the levels of RANKL/OPG, MMP-8 and OSI as well as the role of IL-20 in patients with MetS and periodontitis.MethodsThe study included a total of 80 individuals, divided into four groups: 20 individuals who were healthy both systemically and periodontally, 20 individuals who were systemically healthy but had periodontitis, 20 individuals who had MetS but were periodontally healthy, and 20 individuals who had both MetS and periodontitis. Periodontal clinical parameters (plaque index, gingival index, bleeding on probing, clinical attachment loss, probing pocket depth) were evaluated. Gingival crevicular fluid (GGF) and serum samples were collected and used for biochemical assays. Enzyme-linked immunosorbent assay was used to determine the levels of IL-20, receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG), matrix metalloproteinase-8 (MMP-8) and oxidative stress index (OSI).ResultsIL-20 levels measured in serum and GCF were statistically significantly highest in patients with MetS and periodontitis (p = 0.001). Significant positive correlation was observed between serum and GCF IL-20 values and periodontal parameters (p < 0.05). There was a positive correlation between RANKL and RANKL/OPG levels and IL-20 and clinical parameters (p < 0.05). OSI values were found to be increased in the presence of both periodontitis and MetS (p = 0.001) and were positively correlated with serum and GCF IL-20 (p < 0.05).ConclusionsThese data from the study suggest a correlation between IL-20 and both MetS and periodontitis. IL-20 may potentially worsen the condition of periodontal tissue by increasing both the oxidative stress levels, periodontal collagen degredation and the ratio of RANKL to OPG.Trial registrationThis study was registered on ClinicTrials.gov (NCT06092853), 2023-10-10, retrospectively registered.

Periodontal diseases in Africa.

Periodontal diseases, a group of complex conditions marked by an excessive immune response and periodontal tissue destruction, are a global health concern. Since 1990, the incidence of these diseases has doubled, with Western sub-Saharan Africa experiencing the highest burden. Accurate diagnosis and case identification are crucial for understanding the etiology, features of disease, research, treatment and prevention. Modern perspectives on periodontal disease classification are based on commonality among those affected. However, current literature is often plagued by methodological inconsistencies and focused on disease mechanisms in European populations. Health inequalities in low- and middle-income countries (LMICs) are exacerbated by these challenges, with sub-Saharan Africa, and Nigeria specifically, facing unique difficulties such as clinical personnel shortages and limited research infrastructure. This review explored disparities in periodontal disease research, care and outcomes in African populations. We highlighted these disparities and identified the factors contributing to inequities in periodontal health outcomes. We further demonstrated the critical need for inclusive and equitable healthcare and research practices tailored to the unique challenges faced by diverse populations and regions with limited resources. Addressing these disparities is essential for ensuring that advancements in healthcare are accessible to all, thereby improving global oral health and general health.

COMPARISON OF THE EFFECTIVENESS OF CONSERVATIVE AND SURGIRAL TREATMENT OF GENERALIZED PERIODONTITIS

In the complex treatment of generalized periodontitis, special attention is paid to the correct combination of conservative and surgical methods of treatment, which reduce the activity of destructive processes in periodontal tissues and restore the lost anatomy [1-9]. However, despite various additions and modifications, conservative and surgical interventions on the periodontal itself do not create sufficient conditions for effective relief of pathological processes and restoration of periodontal tissues [10-18]. In some cases, the use of new technologies, including the use of occupational hygiene, dental splints and other conservative methods of treatment, does not lead to the stabilization of destructive processes in the alveolar process, and in some cases contributes to the further destruction of periodontal tissues and surrounding bone tissue with the formation of defects of various sizes. The problem of dental preservation in patients with generalized periodontitis of II-III severity is still relevant. The organizational inconsistency of dentists of different specialties, the lack of a real medical examination of patients with periodontal disease create prerequisites for the interruption of treatment at the level of conservative therapeutic agents and the active course of destruction of bone tissue of alveolar processes.

Advances of Oxidative Stress Impact in Periodontitis: Biomarkers and Effective Targeting Options.

Periodontitis is the most common inflammatory oral disease that affects around 15% of adults and contributes to severe periodontal tissue destruction with subsequent tooth loosening and loss. Among the main pathogenic mechanisms underlying periodontitis, excessive reactive oxygen species production and oxidative stress play a predominant role in inducing both local and systemic damage. Current therapeutic approaches have expanded the conventional methods combined with herbal antioxidant compounds to free radical-scavenging nanomaterials and infrared laser therapy, offering promising pre-clinical evidence in periodontitis management. Herein, we review the pathogenic mechanisms of reactive oxygen species tissue damage, along with recent advances in oxidative stress biomarkers and novel targeting options.

Neutrophils suppress osteogenic differentiation of Gli1+ stem cells via neutrophil extracellular traps and contribute to bone loss in periodontitis

Periodontitis is a severe and chronic oral inflammatory disease that leads to the progressive and irreversible destruction of periodontal tissues, ultimately resulting in tooth loss. Among the immune cell subtypes involved, neutrophils play a crucial role in the initiation and progression of periodontitis. Mesenchymal stem cells (MSCs) are essential components of periodontal tissue, contributing to tissue development, homeostasis, and regeneration. Recent studies have demonstrated that neutrophils significantly affect the function of MSCs by changing the inflammatory environment. However, the specific effects of neutrophils on periodontal MSCs during periodontitis remain unclear, highlighting a gap in our understanding of the disease mechanisms. In this study, we utilized the Gli1-CreERT2;mT/mG transgenic mouse model to specifically mark Gli1+ cells, a critical and representative subset of MSCs in the periodontal tissues responsible for maintaining tissue homeostasis. We reveal that neutrophils inhibit the osteogenic differentiation of Gli1+ cells and exacerbate alveolar bone destruction by secreting neutrophil extracellular traps (NETs), which induce endoplasmic reticulum stress in Gli1+ cells. These findings highlight the pivotal impact of neutrophils on distinct subpopulations of periodontal MSCs in the pathogenesis of periodontitis, offering valuable insights into the underlying mechanisms of the disease and suggesting potential future therapeutic strategies aimed at modulating the interactions between neutrophils and MSCs.

Hierarchically structured nanofibrous scaffolds spatiotemporally mediate the osteoimmune micro-environment and promote osteogenesis for periodontitis-related alveolar bone regeneration

Periodontitis suffer from inflammation-induced destruction of periodontal tissues, resulting in the serious loss of alveolar bone. Controlling inflammation and promoting bone regeneration are two crucial aspects for periodontitis-related alveolar bone defect treatment. Herein, we developed a hierarchically structured nanofibrous scaffold with a nano-embossed sheath and a bone morphogenetic protein 2-loaded core to match the periodontitis-specific features that spatiotemporally modulated the osteoimmune environment and promoted periodontal bone regeneration. We investigated the potential of this unique scaffold to treat periodontitis-related alveolar bone defects in vivo and in vitro. The results demonstrated that the hierarchically structured scaffold effectively reduced the inflammatory levels in macrophages and enhanced the osteogenic potential of bone mesenchymal stem cells in an inflammatory microenvironment. Moreover, in vivo experiments revealed that the hierarchically structured scaffold significantly ameliorated inflammation in the periodontium and inhibited alveolar bone resorption. Notably, the hierarchically structured scaffold also exhibited a prolonged effect on promoting alveolar bone regeneration. These findings highlight the significant therapeutic potential of hierarchically structured nanofibrous scaffolds for the treatment of periodontitis, and their promising role in the field of periodontal tissue regeneration. Statement of significanceWe present a novel hierarchically structured nanofibrous scaffold of coupling topological and biomolecular signals for precise spatiotemporal modulation of the osteoimmune micro-environment. Specifically, the scaffold was engineered via coaxial electrospinning of the poly(ε-caprolactone) sheath and a BMP-2/polyvinyl alcohol core, followed by surface-directed epitaxial crystallization to generate cyclic nano-lamellar embossment on the sheath. With this unique hierarchical structure, the cyclic nano-lamellar sheath provided a direct nano-topographical cue to alleviate the osteoimmune environment, and the stepwise release of BMP-2 from the core provided a biological cue for bone regeneration. This research underscores the potential of hierarchically structured nanofibrous scaffolds as a promising therapeutic approach for periodontal tissue regeneration and highlights their role in advancing periodontal tissue engineering.

Periodontitis Treatment by Scaling and Root Planing with Antimicrobial and Anti-Inflammatory Solutions in a Patient with Systemic Lupus Erythematosus

Introduction: Systemic Lupus Erythematosus is a chronic autoimmune disease of unknown cause in which patients regularly consume immunosuppressants, causing a decrease in body fluids of proteins such as mucins, immunoglobulin A and G antibodies, which causes destruction of periodontal tissue. Objective: To report a clinical case on the benefits of scaling and root planing (srp) with solutions based on hypochlorous acid (HOCl) and modified diallyl disulfide oxide (mddo) in the periodontal inflammatory process in a patient with systemic lupus erythematosus patient, tubulointerstitial nephritis and periodontitis. Case presentation: A 32-year-old woman, with systemic lupus erythematosus, tubulointerstitial nephritis and, according to the 2017 global workshop on the classification of periodontal diseases and conditions, was diagnosed with Stage 2 and Grade B periodontitis. Periodontal assessment revealed a high overall dental plaque index, with high-risk plaque being the most prevalent. srp treatment was carried out by quadrants, applying a HOCl solution during periodontal debridement and periodontal pockets were irrigated with mddo solution to disinfect them. Conclusions: The antimicrobial and anti-inflammatory solutions used as adjuvants to srp in this novel periodontal irrigation therapy helped to reduce gingival inflammation and high-risk plaque, which favoured healing of periodontal tissues in a patient with systemic lupus erythematosus.

Prediabetes Associates with Matrix Metalloproteinase-8 Activation and Contributes to the Rapid Destruction of Periodontal Tissues.

The aim of this cross-sectional study was to investigate the relationship between periodontitis, potential periodontitis oral fluid biomarkers, and prediabetes. This study included 150 Greek adults aged 25 to 78 years who were tested with an Hemoglobin A1C (HBA1c) diagnostic system, an active-matrix metalloproteinase-8 (aMMP-8) point-of-care (PoC) test, and several salivary biomarkers enzyme-linked immunosorbent assay tests and gelatin zymography. A full-mouth clinical examination was performed to assess their periodontal and oral health status. The Kruskal-Wallis test was used to determine the statistically significant difference in the levels of periodontal oral fluid biomarkers between the different periodontitis stages, periodontitis grades, and the stages and grades of periodontitis combined. Spearman's rank correlation was performed to assess the strength and direction of the association between aMMP-8 and HbA1c levels (<5.7 and ≥5.7%) and with the other oral fluid biomarkers among patients with severe periodontitis. A two-sided p-value below 0.05 was considered statistically significant in this study. aMMP-8, but not total MMP-8 or other biomarkers, associated significantly with the stage and grade of periodontitis combined (p < 0.001, Kruskal-Wallis test). Among stage III grade C periodontitis patients, aMMP-8 levels were significantly positively correlated with prediabetes (Spearman's rho = 0.646, p = 0.044), total MMP-8 (rho = 0.636, p = 0.048), PMN Elastase (rho = 0.729, p = 0.017), total MMP-9 (rho = 0.721, p = 0.019), and total MMP-8/TIMP-1 molar ratio (rho = 0.879, p < 0.001). Prediabetic disease development can upregulate MMP-8 expression (total MMP-8) in rapidly progressing, severe periodontitis, where MMP-8 latent species are further activated into their active forms (aMMP-8). Simultaneously, several proinflammatory biomarker levels are elevated in this tissue-destructive biomarker cascade. This development is easily detectable online/in real-time within 5 minutes by aMMP-8 PoC testing at the dentist's office.

Allyl isothiocyanate suppressed periodontal tissue destruction in mice via bacteriostatic and anti-inflammatory activities against Porphyromonas gingivalis

ObjectivesAllyl isothiocyanate (AITC) is a phytochemical that is abundantly present in cruciferous vegetables, such as wasabi and mustard. Among its pharmacological properties, it demonstrates anticancer, antifungal, and anti-inflammatory activities. This study aimed to investigate the functions of AITC against periodontopathic bacteria and its effects on a mouse model of periodontitis. DesignThe antimicrobial and antibiofilm functions of AITC were assessed against Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mitis. To clarify its anti-inflammatory effects, macrophage-like cells from THP-1 were stimulated with P. gingivalis lipopolysaccharide (LPS), and the release of inflammatory cytokines was analyzed by ELISA. Experimental periodontitis was induced in 9-week-old mice by ligation and oral infection of P. gingivalis, and AITC was injected into the gingiva once daily for 8 days. Alveolar bone resorption was evaluated by measuring the exposed root area. Gene expressions in the periodontal tissue were analyzed via qPCR. ResultsAITC exerted weak bacteriostatic effects against P. gingivalis, inhibiting biofilm formation. AITC also impeded the production of interleukin-6 and tumor necrosis factor-α induced by P. gingivalis LPS. Additionally, transient receptor potential ankyrin 1(TRPA1) channel agonist inhibited the anti-inflammatory effects of AITC. In vivo, AITC inhibited alveolar bone destruction and decreased the gene transcription of Il6 in the periodontal tissue. ConclusionAITC exerted weak bacteriostatic and anti-inflammatory effects against P. gingivalis, reducing alveolar bone destruction and suppressing the inflammatory response in experimental periodontitis. Therefore, AITC may serve as a valuable adjunct in controlling periodontal disease.

Inflammation indices in association with periodontitis and cancer.

Inflammation is a complex physiological process that plays a pivotal role in many if not all pathological conditions, including infectious as well as inflammatory diseases, like periodontitis and autoimmune disorders. Inflammatory response to periodontal biofilms and tissue destruction in periodontitis is associated with the release of inflammatory mediators. Chronic inflammation can promote the development of cancer. Persistence of inflammatory mediators plays a crucial role in this process. Quantification and monitoring of the severity of inflammation in relation to cancer is essential. Periodontitis is mainly quantified based on the severity and extent of attachment loss and/or pocket probing depth, in addition with bleeding on probing. In recent years, studies started to investigate inflammation indices in association with periodontal diseases. To date, only few reviews have been published focusing on the relationship between blood cell count, inflammation indices, and periodontitis. This review presents a comprehensive overview of different systemic inflammation indices, their methods of measurement, and the clinical applications in relation to periodontitis and cancer. This review outlines the physiological basis of inflammation and the underlying cellular and molecular mechanisms of the parameters described. Key inflammation indices are commonly utilized in periodontology such as the neutrophil to lymphocyte ratio. Inflammation indices like the platelet to lymphocyte ratio, platelet distribution width, plateletcrit, red blood cell distribution width, lymphocyte to monocyte ratio, delta neutrophil index, and the systemic immune inflammation index are also used in hospital settings and will be discussed. The clinical roles and limitations, relationship to systemic diseases as well as their association to periodontitis and treatment response are described.

Bmi‐1 alleviates alveolar bone resorption through the regulation of autophagy

AbstractBackgroundB‐cell‑specific Moloney MLV insertion site‐1(Bmi‐1)is a crucial osteopenic target molecule. The aim of this study is to explore the effects of Bmi‐1 on alveolar bone resorption and the underlying mechanisms in vitro and vivo.MethodsA Bmi‐1‐knockout (Bmi‐1−/−) mouse model was used to investigate the effect of Bmi‐1 on alveolar bone metabolism, with micro‐computed tomography imaging, histology, and immunohistochemistry staining. Furthermore, we utilized a ligature‐induced experimental periodontitis model to examine the impact of Bmi‐1‐knockdown (Bmi‐1±) on inflammatory alveolar bone resorption. Finally, we stimulated human periodontal ligament stem cells (hPDLSCs) with lipopolysaccharide (LPS) to explore the potential mechanism of Bmi‐1 overexpression in the process of osteogenesis.ResultsCompared with wild‐type mice, Bmi‐1−/− mice demonstrated more alveolar bone resorption by inhibiting osteogenesis, which was characterized by decreases in Runt‐related transcription factor 2 and type 1 collagen formation. In addition, Bmi‐1−/− mice had lower levels of autophagy markers such as Parkin and LC3, but higher levels of inflammation‐related factors such as interleukin (IL)‐6 and IL‐1β in periodontal tissues. In addition, Bmi‐1‐knockdown aggravated ligature‐induced alveolar bone loss. Under in vitro inflammatory conditions, Bmi‐1 overexpression stimulated osteoblast differentiation and inhibited the production of inflammatory factors, as well as the autophagy and apoptosis in hPDLSCs stimulated with LPS. When 3‐methyladenine (3‐MA), an autophagy inhibitor, was added, the osteogenic effect of Bmi‐1 was further enhanced.ConclusionsBmi‐1 alleviates alveolar bone resorption by regulating autophagy, indicating that it could be a potential target for periodontitis prevention and treatment.Plain Language SummaryPeriodontitis is a chronic inflammatory disease, which leads to progressive destruction of periodontal tissues, manifested as periodontal pocket formation, loss of periodontal attachment and alveolar bone resorption. Currently, there is a lack of effective treatments to regenerate damaged periodontal tissues. Therefore, it is of great clinical significance to explore new mechanisms of periodontitis and effective intervention targets. B‐cell‑specific Moloney MLV insertion site‐1 (Bmi‐1) is involved in the regulation of the cell cycle, DNA damage repair, autophagy, bone metabolism, tumor, and other physiopathological processes. Autophagy, as an important mechanism of intracellular self‐regulation, plays an indispensable role in the destruction and repair of periodontal tissues. The aim of this study was to investigate the role of Bmi‐1 on periodontal tissues and its intrinsic mechanism. The results revealed that Bmi‐1 regulates autophagy to protect periodontal tissues, suggesting that it may be a potential target for the prevention and treatment of periodontitis.

The Clinical Effect of a Propolis and Mangosteen Extract Complex in Subjects with Gingivitis: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

This study investigated the efficacy and safety of a propolis-mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multicentered, randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on the changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. The results revealed that the PMEC group showed a significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p < 0.0001) at 8 weeks, including substantial reductions in IL-1β, PGE2, MMP-8, and MMP-9 levels compared to the baseline. While clinical parameters trended towards improvement in both groups, the intergroup differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

An NIR-propelled janus nanomotor with enhanced ROS-scavenging, immunomodulating and biofilm-eradicating capacity for periodontitis treatment

Periodontitis is an inflammatory disease caused by bacterial biofilms, which leads to the destruction of periodontal tissue. Current treatments, such as mechanical cleaning and antibiotics, struggle to effectively address the persistent biofilms, inflammation, and tissue damage. A new approach involves developing a Janus nanomotor (J-CeM@Au) by coating cerium dioxide-doped mesoporous silica (CeM) with gold nanoparticles (AuNPs). This nanomotor exhibits thermophoretic motion when exposed to near-infrared (NIR) laser light due to the temperature gradient produced by the photothermal effects of asymmetrically distributed AuNPs. The NIR laser provides the energy for propulsion and activates the nanomotor's antibacterial properties, allowing it to penetrate biofilms and kill bacteria. Additionally, the nanomotor's ability to scavenge reactive oxygen species (ROS) can modulate the immune response and create a regenerative environment, promoting the healing of periodontal tissue. Overall, this multifunctional nanomotor offers a promising new approach for treating periodontitis by simultaneously addressing biofilm management and immune modulation with autonomous movement.

Developments in Alloplastic Bone Grafts and Barrier Membrane Biomaterials for Periodontal Guided Tissue and Bone Regeneration Therapy.

Periodontitis is a serious form of oral gum inflammation with recession of gingival soft tissue, destruction of the periodontal ligament, and absorption of alveolar bone. Management of periodontal tissue and bone destruction, along with the restoration of functionality and structural integrity, is not possible with conventional clinical therapy alone. Guided bone and tissue regeneration therapy employs an occlusive biodegradable barrier membrane and graft biomaterials to guide the formation of alveolar bone and tissues for periodontal restoration and regeneration. Amongst several grafting approaches, alloplastic grafts/biomaterials, either derived from natural sources, synthesization, or a combination of both, offer a wide variety of resources tailored to multiple needs. Examining several pertinent scientific databases (Web of Science, Scopus, PubMed, MEDLINE, and Cochrane Library) provided the foundation to cover the literature on synthetic graft materials and membranes, devoted to achieving periodontal tissue and bone regeneration. This discussion proceeds by highlighting potential grafting and barrier biomaterials, their characteristics, efficiency, regenerative ability, therapy outcomes, and advancements in periodontal guided regeneration therapy. Marketed and standardized quality products made of grafts and membrane biomaterials have been documented in this work. Conclusively, this paper illustrates the challenges, risk factors, and combination of biomaterials and drug delivery systems with which to reconstruct the hierarchical periodontium.

Mitochondria-targeted drug delivery system based on tetrahedral framework nucleic acids for bone regeneration under oxidative stress

Oxidative stress is present in many diseases and severely affects tissue reconstruction and regeneration. Many traditional Chinese medicinal monomers have excellent antioxidant effects; however, most cannot target the mitochondria, where oxidative stress is produced. In this study, a mitochondria-targeted antioxidant delivery system based on tetrahedral framework nucleic acids (tFNAs) is developed to combat oxidative stress. Antioxidant quercetin cargoes can be effectively loaded into the tFNA “trucks”, and the trucks are modified with mitochondria-targeting molecules to act as “headlights” to efficiently transport the cargo to the mitochondria. These results confirm that the delivery system can be efficiently loaded with quercetin and target the mitochondria. Both in vitro and in vivo studies confirm that the delivery system resists oxidative stress and inflammatory responses in a diabetic periodontitis model, which suffers from severe oxidative stress. The constructed delivery system delays the destruction of periodontal tissues, and promotes periodontal tissue regeneration. This study provides a new strategy for the efficient and targeted delivery of antioxidants, which is of great significance for the therapy of oxidative stress-related diseases and tissue regeneration.

Impact of Periodontitis on Endothelial Risk Dysfunction and Oxidative Stress Improvement in Patients with Cardiovascular Disease.

Periodontitis is a multifactorial chronic inflammatory disease that affects the periodontium and overall oral health and is primarily caused by a dysbiotic gingival biofilm, which includes, among others, Gram-negative bacteria such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Tannerella forsythensis that colonize gingival tissues and that can lead, if not properly treated, to periodontal tissue destruction and tooth loss. In the last few decades, several large-scale epidemiological studies have evidenced that mild and severe forms of periodontitis are strictly bilaterally associated with several cardiovascular diseases (CVDs), stroke, and endothelial dysfunction. Specifically, it is hypothesized that patients with severe periodontitis would have compromised endothelial function, a crucial step in the pathophysiology of atherosclerosis and several CVD forms. In this regard, it was postulated that periodontal treatment would ameliorate endothelial dysfunction, hence bolstering the notion that therapeutic approaches targeted at diminishing cardiovascular risk factors and different forms of periodontal treatment could improve several CVD biomarker outcomes in the short- and long-term in CVD patients. The aim of this review is to update and analyze the link between periodontitis and CVD, focusing on the inflammatory nature of periodontitis and its correlation with CVD, the effects of periodontal therapy on endothelial dysfunction and oxidative stress, and the impact of such therapy on CVD biomarkers and outcomes. The article also discusses future research directions in this field.

Neural epidermal growth factor-like 1 protein (Nell-1) alleviates periodontal tissue destruction in periodontitis by regulating the ratio of M2/M1 macrophage phenotypes

BackgroundPeriodontitis is a common oral disease with high prevalence worldwide. Neural epidermal growth factor-like 1 protein (Nell-1) has recently been reported to have anti-inflammation effects and may be a drug candidate for osteoarthritis. However, its immunotherapeutic effects in periodontitis remain unknown. Therefore, this study aimed to investigate the effects of Nell-1 on periodontitis in terms of macrophage polarization and analyze its possible underlying mechanism. MethodsA rat ligation-induced experimental periodontitis model was established and locally injected with Nell-1 (n = 6/group). Periodontal tissue destruction and macrophage polarization in vivo were analyzed using micro-CT, histology analysis, and western blot. Enzyme-linked immunosorbent assay was used to evaluate serum inflammatory cytokines. Then, the RAW 264.7 macrophage cells were treated with lipopolysaccharide (LPS), Nell-1, and the c-Jun N-terminal kinases (JNK) inhibitor (SP600125). RT-PCR, western blot, and flow cytometry were performed to further analyze the effect of Nell-1 on macrophage polarization and the underlying mechanism in vitro. ResultsLocal treatment with Nell-1 significantly alleviated the destruction of alveolar bone and fibers in periodontitis, and upregulated the ratio of M2/M1 macrophages in periodontal tissues (P < 0.05). In vitro, Nell-1 at the concentrations of 200 and 500 ng/mL could significantly inhibit the expression of M1-related inflammatory factors in LPS-stimulated macrophages, and increase the expression of M2-related markers, regulating the macrophage phenotype switch into M2 (P < 0.05). The mRNA of JNK and relative protein level of phospho-JNK/JNK were also upregulated by Nell-1 (P < 0.05). Additionally, the JNK inhibitor (SP600125) could reverse the effect of Nell-1 on macrophage polarization (P < 0.05). ConclusionsNell-1 could modulate the ratio of M2/M1 macrophages possibly through the JNK/MAPK signaling pathway, subsequently attenuating the inflammation and destruction of periodontal tissues caused by periodontitis.

Toll-like receptor 4 deficiency affects the balance of osteoclastogenesis and osteoblastogenesis in periodontitis

Toll-like receptor 4 (TLR4) acts as a double-edged sword in the occurrence and development of periodontitis. While the activation of TLR4 in macrophages aids in clearing local pathogens, it can also disrupt innate immune responses, upsetting microecological balance and accelerating the destruction of periodontal bone tissues. To date, the effects of TLR4 on osteogenesis and osteoclastogenesis in periodontitis have not been comprehensively studied.In this study, we investigated the development of periodontitis in the Tlr4−/− mice by ligating their second molars with silk threads. Compared to wild-type (WT) mice, Tlr4−/− mice demonstrated increased resistance to periodontitis-associated bone destruction, as evidenced by decreased bone resorption and enhanced bone regeneration. Mechanistically, the deletion of Tlr4 not only inhibited osteoclast formation by reducing the expression of NFATc1, CTSK and TRAP, but also enhanced osteogenic abilities through increased expression of OCN, OPN and RUNX2. In conclusion, TLR4 tips the balance of osteoclastogenesis and osteogenesis, thereby promoting periodontal bone destruction in periodontitis.