Browsing by Subject "Periodontitis"
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Item A Highly Ordered, Nanostructured Fluorinated CaP-Coated Melt Electrowritten Scaffold for Periodontal Tissue Regeneration(Wiley, 2021) Daghrery, Arwa; Ferreira, Jessica A.; de Souza Araújo, Isaac J.; Clarkson, Brian H.; Eckert, George J.; Bhaduri, Sarit B.; Malda, Jos; Bottino, Marco C.; Biostatistics, School of Public HealthPeriodontitis is a chronic inflammatory, bacteria-triggered disorder affecting nearly half of American adults. Although some level of tissue regeneration is realized, its low success in complex cases demands superior strategies to amplify regenerative capacity. Herein, highly ordered scaffolds are engineered via Melt ElectroWriting (MEW), and the effects of strand spacing, as well as the presence of a nanostructured fluorinated calcium phosphate (F/CaP) coating on the adhesion/proliferation, and osteogenic differentiation of human-derived periodontal ligament stem cells, are investigated. Upon initial cell-scaffold interaction screening aimed at defining the most suitable design, MEW poly(𝝐-caprolactone) scaffolds with 500 µm strand spacing are chosen. Following an alkali treatment, scaffolds are immersed in a pre-established solution to allow for coating formation. The presence of a nanostructured F/CaP coating leads to a marked upregulation of osteogenic genes and attenuated bacterial growth. In vivo findings confirm that the F/CaP-coated scaffolds are biocompatible and lead to periodontal regeneration when implanted in a rat mandibular periodontal fenestration defect model. In aggregate, it is considered that this work can contribute to the development of personalized scaffolds capable of enabling tissue-specific differentiation of progenitor cells, and thus guide simultaneous and coordinated regeneration of soft and hard periodontal tissues, while providing antimicrobial protection.Item Advanced biomaterials for periodontal tissue regeneration(Wiley, 2022) Daghrery, Arwa; Bottino, Marco C.; Biomedical and Applied Sciences, School of DentistryThe periodontium is a suitable target for regenerative intervention, since it does not functionally restore itself after disease. Importantly, the limited regeneration capacity of the periodontium could be improved with the development of novel biomaterials and therapeutic strategies. Of note, the regenerative potential of the periodontium depends not only on its tissue‐specific architecture and function, but also on its ability to reconstruct distinct tissues and tissue interfaces, suggesting that the advancement of tissue engineering approaches can ultimately offer new perspectives to promote the organized reconstruction of soft and hard periodontal tissues. Here, we discuss material‐based, biologically active cues, and the application of innovative biofabrication technologies to regenerate the multiple tissues that comprise the periodontium.Item Advanced Scaffolds for Dental Pulp and Periodontal Regeneration(Elsevier, 2017-10) Bottino, Marco C.; Pankajakshan, Divya; Nör, Jacques E.; Biomedical Sciences and Comprehensive Care, School of DentistryNo current therapy promotes root canal disinfection and regeneration of the pulp-dentin complex in cases of pulp necrosis. Antibiotic pastes used to eradicate canal infection negatively affect stem cell survival. Three-dimensional easy-to-fit antibiotic-eluting nanofibers, combined with injectable scaffolds, enriched or not with stem cells and/or growth factors, may increase the likelihood of achieving predictable dental pulp regeneration. Periodontitis is an aggressive disease that impairs the integrity of tooth-supporting structures and may lead to tooth loss. The latest advances in membrane biomodification to endow needed functionalities and technologies to engineer patient-specific membranes/constructs to amplify periodontal regeneration are presented.Item Alveolar bone protection by targeting the SH3BP2-SYK axis in osteoclasts(Wiley, 2020-02) Kittaka, Mizuho; Yoshimoto, Tetsuya; Schlosser, Collin; Rottapel, Robert; Kajiya, Mikihito; Kurihara, Hidemi; Reichenberger, Ernst J.; Ueki, Yasuyoshi; Biomedical Sciences and Comprehensive Care, School of DentistryPeriodontitis is a bacterially induced chronic inflammatory condition of the oral cavity where tooth-supporting tissues including alveolar bone are destructed. Previously, we have shown that the adaptor protein SH3-domain binding protein 2 (SH3BP2) plays a critical role in inflammatory response and osteoclastogenesis of myeloid lineage cells through spleen tyrosine kinase (SYK). In this study, we show that SH3BP2 is a novel regulator for alveolar bone resorption in periodontitis. Micro-CT analysis of SH3BP2-deficient (Sh3bp2 -/- ) mice challenged with ligature-induced periodontitis revealed that Sh3bp2 -/- mice develop decreased alveolar bone loss (male 14.9% ± 10.2%; female 19.0% ± 6.0%) compared with wild-type control mice (male 25.3% ± 5.8%; female 30.8% ± 5.8%). Lack of SH3BP2 did not change the inflammatory cytokine expression and osteoclast induction. Conditional knockout of SH3BP2 and SYK in myeloid lineage cells with LysM-Cre mice recapitulated the reduced bone loss without affecting both inflammatory cytokine expression and osteoclast induction, suggesting that the SH3BP2-SYK axis plays a key role in regulating alveolar bone loss by mechanisms that regulate the bone-resorbing function of osteoclasts rather than differentiation. Administration of a new SYK inhibitor GS-9973 before or after periodontitis induction reduced bone resorption without affecting inflammatory reaction in gingival tissues. In vitro, GS-9973 treatment of bone marrow-derived M-CSF-dependent macrophages suppressed tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation with decreased mineral resorption capacity even when GS-9973 was added after RANKL stimulation. Thus, the data suggest that SH3BP2-SYK is a novel signaling axis for regulating alveolar bone loss in periodontitis and that SYK can be a potential therapeutic target to suppress alveolar bone resorption in periodontal diseases.Item Are Adults Over 18 Years of Age with Anaemia More Likely to Develop Chronic Periodontitis Than Adults Without Anaemia? - A Systematic Review and Meta-Analysis(Wolters Kluwer, 2023-08-30) Roberts, Madison; Jimson, Sudha; Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of DentistryAims and objectives: Periodontitis is a chronic disease affecting the supporting tissues of the teeth and exhibits bidirectional relation with systemic diseases. This study aims to determine the association between chronic periodontitis and erythrocyte functional measures: total red blood cells (RBCs), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC) by systematic review and meta-analysis. Materials and methods: A systematic search of the electronic databases PUBMED, OVID, Embase, Web on Science, and Google Scholar was undertaken from inception to July 2022. English language studies that evaluated the erythrocyte functional measures in periodontitis and health were selected. Other review reports, letters/opinion articles, studies without a definition of periodontitis, and the concomitant presence of systemic conditions (diabetes, kidney disease, cancer) were excluded. Two reviewers determined full-text eligibility in a blinded process. Meta-Essentials software was used to generate forest plots and to determine heterogeneity and publication bias. Results: Twenty-six studies involving 1082 patients with chronic periodontitis and 980 healthy controls were analyzed. Pooled results showed lower Hb concentration (Hedges' g = -1.16; 95% confidence intervals [CI], -1.7 to -0.62), RBC counts (Hedges' g = -0.85; 95% CI, -1.31 to -0.38) and packed cell volume (-0.56; 95% CI, -1.02 to -0.11) in patients with chronic periodontitis. Conclusion: This meta-analysis showed a decreasing trend in the hematological parameters, including hemoglobin concentration, number of erythrocytes, and hematocrit in patients with chronic periodontitis compared to healthy controls.Item Associations between Oral Health and Cannabis Use among Adolescents and Young Adults: Implications for Orthodontists(MDPI, 2022-11-18) Le, Austin; Khoo, Edmund; Palamar, Joseph J.; Orthodontics and Oral Facial Genetics, School of DentistryCannabis use is prevalent among adolescents and young adults in the US. Virtually all modes of cannabis consumption involve the oral cavity, and previous studies have linked cannabis use with poorer oral health. We sought to identify associations between cannabis use and various oral health outcomes and behaviors among individuals 12–25 years of age, and to discuss implications for orthodontists who largely interact with this age group over an extended period of treatment time. We examined data from patient electronic health records (N = 14,657) obtained between 2015 and 2021. Associations between lifetime and current self-reported cannabis use and several oral health outcomes or related behaviors that reflect periodontal health, caries status, oral lesions, and physical integrity of tooth structure and restorations were examined in a bivariable and multivariable manner, controlling for patient age, sex, and self-reported tobacco and alcohol use. Reporting lifetime cannabis use was associated with higher risk for having oral lesions (aPR = 1.41, 95% CI: 1.07–1.85), bruxism (aPR = 1.31, 95% CI: 1.09–1.58), and frequent consumption of sugary beverages and snacks (aPR = 1.27, 95% CI: 1.12–1.41). Reporting current cannabis use was associated with higher risk for oral lesions (aPR = 1.45, 95% CI: 1.03–2.06) and frequent consumption of sugary beverages and snacks (aPR = 1.26, 95% CI: 1.07–1.48). Cannabis users aged 12–25 are at increased risk for bruxism, oral lesions, and frequent consumption of sugary beverages and snacks. Orthodontists and other dental professionals should probe for drug use and be cognizant of increased risk for oral health problems in patients that report actively using cannabis.Item Biodegradable nanofibrous drug delivery systems: effects of metronidazole and ciprofloxacin on periodontopathogens and commensal oral bacteria(Springer-Verlag, 2014-12) Bottino, Marco C.; Arthur, Rodrigo A.; Waeiss, R. Aaron; Kamocki, Krzysztof; Gregson, Karen S.; Gregory, Richard L.; Department of Restorative Dentistry, IU School of DentistryOBJECTIVES: The purposes of this study were to fabricate biodegradable polydioxanone (PDS II®) electrospun periodontal drug delivery systems (hereafter referred to as matrices) containing either metronidazole (MET) or ciprofloxacin (CIP) and to investigate the effects of antibiotic incorporation on both periodontopathogens and commensal oral bacteria. MATERIALS AND METHODS: Fibrous matrices were processed from PDS polymer solution by electrospinning. Antibiotic-containing PDS solutions were prepared to obtain four distinct groups: 5 wt.% MET, 25 wt.% MET, 5 wt.% CIP, and 25 wt.% CIP. Pure PDS was used as a control. High-performance liquid chromatography (HPLC) was done to evaluate MET and CIP release. Dual-species biofilms formed by Lactobacillus casei (Lc) and Streptococcus salivarius (Ss) were grown on the surface of all electrospun matrices. After 4 days of biofilm growth, the viability of bacteria on biofilms was assessed. Additionally, antimicrobial properties were evaluated against periodontopathogens Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa) using agar diffusion assay. RESULTS: A three-dimensional interconnected porous network was observed in the different fabricated matrices. Pure PDS showed the highest fiber diameter mean (1,158 ± 402 nm) followed in a descending order by groups 5 wt.% MET (1,108 ± 383 nm), 25 wt.% MET (944 ± 392 nm), 5 wt.% CIP (871 ± 309 nm), and 25 wt.% CIP (765 ± 288 nm). HPLC demonstrated that groups containing higher amounts (25 wt.%) of incorporated drugs released more over time, while those with lower levels (5 wt.%) the least. No inhibitory effect of the tested antibiotics was detected on biofilm formation by the tested commensal oral bacteria. Meanwhile, CIP-containing matrices inhibited growth of Fn and Aa. CONCLUSION: CIP-containing matrices led to a significant inhibition of periodontopathogens without negatively impairing the growth of periodontal beneficial bacteria. CLINICAL RELEVANCE: Based on the proven in vitro inhibition of periodontitis-related bacteria, future in vivo research using relevant animal models is needed to confirm the effectiveness of these drug delivery systems.Item Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss(Elsevier, 2024) Wang, Hui; Divaris, Kimon; Pan, Bohu; Li, Xiaofei; Lim, Jong-Hyung; Saha, Gundappa; Barovic, Marko; Giannakou, Danai; Korostoff, Jonathan M.; Bing, Yu; Sen, Souvik; Moss, Kevin; Wu, Di; Beck, James D.; Ballantyne, Christie M.; Natarajan, Pradeep; North, Kari E.; Netea, Mihai G.; Chavakis, Triantafyllos; Hajishengallis, George; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthClonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3aR878H/+ bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss.Item Contribution of Porphyromonas gingivalis lipopolysaccharide to experimental periodontitis in relation to aging(Springer, 2021) Akkaoui, Juliet; Yamada, Chiaki; Duarte, Carolina; Ho, Anny; Vardar-Sengul, Saynur; Kawai, Toshihisa; Movila, Alexandru; Biomedical and Applied Sciences, School of DentistryAging is associated with increased prevalence and severity of pathogenic outcomes of periodontal disease, including soft tissue degeneration and bone loss around the teeth. Although lipopolysaccharide (LPS) derived from the key periodontal pathogen Porphyromonas gingivalis (Pg) plays an important role in the promotion of inflammation and osteoclastogenesis via toll-like receptor (TLR)4 signaling, its pathophysiological role in age-associated periodontitis remains unclear. This study investigated the possible effects of Pg-LPS on RANKL-primed osteoclastogenesis and ligature-induced periodontitis in relation to aging using young (2 months old) and aged (24 months old) mice. To the best of our knowledge, our results indicated that expression of TLR4 was significantly diminished on the surface of osteoclast precursors isolated from aged mice compared with that of young mice. Furthermore, our data demonstrated that the TLR4 antagonist (TAK242) dramatically decreased the numbers of tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts differentiated from RANKL-primed young osteoclast precursors (OCPs) compared with those isolated from aged mice in response to Pg-LPS. In addition, using a ligature-induced periodontitis mouse model, we demonstrated that Pg-LPS elevated (1) secretion of senescence-associated secretory phenotype (SASP) markers, including the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, as well as osteoclastogenic RANKL, and (2) the number of OCPs and TRAP+ osteoclasts in the periodontal lesion induced in young mice. In contrast, Pg-LPS had little, or no, effect on the promotion of periodontitis inflammation induced in aged mice. Altogether, these results indicated that periodontal disease in older mice occurs in a manner independent of canonical signaling elicited by the Pg-LPS/TLR4 axis.Item Development and characterization of novel ZnO-loaded electrospun membranes for periodontal regeneration(Elsevier, 2015-09) Münchow, Eliseu A.; Albuquerque, Maria Tereza P.; Zero, Bianca; Kamocki, Krzysztof; Piva, Evandro; Gregory, Richard L.; Bottino, Marco C.; Department of Restorative Dentistry, IU School of DentistryOBJECTIVES: This study reports on the synthesis, materials characterization, antimicrobial capacity, and cytocompatibility of novel ZnO-loaded membranes for guided tissue/bone regeneration (GTR/GBR). METHODS: Poly(ɛ-caprolactone) (PCL) and PCL/gelatin (PCL/GEL) were dissolved in hexafluoropropanol and loaded with ZnO at distinct concentrations: 0 (control), 5, 15, and 30wt.%. Electrospinning was performed using optimized parameters and the fibers were characterized via scanning and transmission electron microscopies (SEM/TEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), contact angle (CA), mechanical testing, antimicrobial activity against periodontopathogens, and cytotoxicity test using human dental pulp stem cells (hDPSCs). Data were analyzed using ANOVA and Tukey (α=5%). RESULTS: ZnO nanoparticles were successfully incorporated into the overall submicron fibers, which showed fairly good morphology and microstructure. Upon ZnO nanoparticles' incorporation, the PCL and PCL/GEL fibers became thicker and thinner, respectively. All GEL-containing membranes showed lower CA than the PCL-based membranes, which were highly hydrophobic. Overall, the mechanical properties of the membranes were reduced upon ZnO incorporation, except for PCL-based membranes containing ZnO at the 30wt.% concentration. The presence of GEL enhanced the stretching ability of membranes under wet conditions. All ZnO-containing membranes displayed antibacterial activity against the bacteria tested, which was generally more pronounced with increased ZnO content. All membranes synthesized in this study demonstrated satisfactory cytocompatibility, although the presence of 30wt.% ZnO led to decreased viability. SIGNIFICANCE: Collectively, this study suggests that PCL- and PCL/GEL-based membranes containing a low content of ZnO nanoparticles can potentially function as a biologically safe antimicrobial GTR/GBR membrane.