Estimating Periodontitis Susceptibility Cases for Epidemiological Studies with Multiple Imputation.

KNOWLEDGE TRANSFER STATEMENT: Our proposed estimate of periodontitis susceptibility cases addresses the issue of missing teeth, offering an innovative solution through a generative missing data imputation model. The implications of our findings extend to fostering more robust investigations into the relationships between periodontal health and systemic diseases, thereby offering valuable insights to clinicians for informed decision-making. Moreover, the study's capacity to shape clinical practices and interventions in public health will further fortify health policy strategies.

Human Histologic Analysis of Implant Osseointegration in a Healed Site Grafted with Nondemineralized Autologous Tooth-Derived Graft Material.

Autologous tooth-derived grafts (ATDGs) have gained popularity as bone substitute biomaterials, owing to their promising healing dynamics in vivo and to patient preference for repurposing hopeless teeth. Nonetheless, concerns exist regarding the biologic response of these ATDGs in preparation for implant placement and subsequent osseointegration. After 12 weeks of extraction socket healing, an implant with an acid-etched surface was placed using osseodensification osteotomy preparation and was retrieved after 16 weeks of integration. Histologic analysis revealed ≥ 64% of direct bone-to-implant contact at multiple regions of interest along the implant surface. Residual dentin particles were scarce and were never found in contact with the implant, suggesting that the ATDG did not interfere with implant osseointegration. Despite the overall trabecular structure of the adjacent maxillary bone with large marrow spaces, the implant surface was delineated with a continuous dense mineralized zone (thickness of 2 to 5 cell layers) with vital osteoblasts in the lacunae. These results suggest that the healing dynamics of ATDG are well aligned with implant osseointegration dynamics.

Osteoimmune regulation underlies oral implant osseointegration and its perturbation.

In the field of biomaterials, an endosseous implant is now recognized as an osteoimmunomodulatory but not bioinert biomaterial. Scientific advances in bone cell biology and in immunology have revealed a close relationship between the bone and immune systems resulting in a field of science called osteoimmunology. These discoveries have allowed for a novel interpretation of osseointegration as representing an osteoimmune reaction rather than a classic bone healing response, in which the activation state of macrophages ((M1-M2 polarization) appears to play a critical role. Through this viewpoint, the immune system is responsible for isolating the implant biomaterial foreign body by forming bone around the oral implant effectively shielding off the implant from the host bone system, i.e. osseointegration becomes a continuous and dynamic host defense reaction. At the same time, this has led to the proposal of a new model of osseointegration, the foreign body equilibrium (FBE). In addition, as an oral wound, the soft tissues are involved with all their innate immune characteristics. When implant integration is viewed as an osteoimmune reaction, this has implications for how marginal bone is regulated. For example, while bacteria are constitutive components of the soft tissue sulcus, if the inflammatory front and immune reaction is at some distance from the marginal bone, an equilibrium is established. If however, this inflammation approaches the marginal bone, an immune osteoclastic reaction occurs and marginal bone is removed. A number of clinical scenarios can be envisioned whereby the osteoimmune equilibrium is disturbed and marginal bone loss occurs, such as complications of aseptic nature and the synergistic activation of pro-inflammatory pathways (implant/wear debris, DAMPs, and PAMPs). Understanding that an implant is a foreign body and that the host reacts osteoimmunologically to shield off the implant allows for a distinction to be drawn between osteoimmunological conditions and peri-implant bone loss. This review will examine dental implant placement as an osteoimmune reaction and its implications for marginal bone loss.

Transcriptome-wide Gene Expression Analysis in Peri-implantitis Reveals Candidate Cellular Pathways.

OBJECTIVE: Peri-implantitis is a condition resulting in destructive inflammation in the peri-implant soft tissue barrier. Clinically, it demonstrates vast clinical differences to periodontitis that suggest distinct inflammatory mechanisms. Implant-derived titanium particles (i-TiPs) frequently found around diseased implants appear to alter the microenvironment and confer resistance to antibiotic treatments. Studies in orthopedic implants have demonstrated potent inflammatory responses to i-TiPs involving a variety of cell types in aseptic conditions. Nonetheless, the genetic programs of cells surveilling and supporting the peri-implant soft tissue barrier in response to the combined challenges of biomaterial degradation products and oral bacteria are poorly defined. Thus, we studied gene expression specific to oral peri-implant inflammatory disease. METHODS: Peri-implant tissues were collected from healthy or diseased implants (N = 10) according to the 2018 classification criteria. Following RNA extraction and purification, a gene-level view of the transcriptome was obtained via a next-generation transcriptome-wide microarray profiling workflow (Clariom S; Applied Biosystems) that covers >20,000 well-annotated genes. A discovery analysis assessed global differential expression of genes and identified pathways in peri-implant health versus disease. RESULTS: Genes involved in the endosomal-lysosomal pathway, such as actin polymerization, were strongly upregulated in diseased tissues (P < .05), proposing increased intracellular activities in response to bacteria and i-TiPs. Cellular respiration pathways involved in oxidative stress were highly transcribed in all peri-implant samples, suggesting that implant-specific factors may trigger a constant state of oxidative stress. CONCLUSION: Within the limitations of this discovery study, expressive upregulation of genes in the endosomal-lysosomal and oxidative stress pathway suggests that inflammation related to receptor-driven responses to extracellular signals, such as i-TiPs and pathogens, may have a crucial role in peri-implantitis. Results warrant external replication in validation cohorts. KNOWLEDGE TRANSFER STATEMENT: Our findings regarding physiologic processes affected by peri-implantitis could advance knowledge of the mechanisms and consequences of the disease. Understanding the cellular programs that partake in peri-implant inflammation has the potential to translate to novel treatment strategies for patients with peri-implantitis.

Association of Global DNA Methylation to Titanium and Peri-Implantitis: A Case-Control Study.

INTRODUCTION: Epigenetic changes are associated with various inflammatory diseases and are influenced by environmental factors. Recent data support an association between titanium dissolution products and peri-implantitis. We hypothesize that site-specific changes in gene methylation, a form of epigenetic regulation, around dental implants may be influenced by local environmental factors, such as titanium dissolution particles. OBJECTIVES: The primary purpose of this study was to assess global methylation patterns related to the disease status of dental implants and the concentration of titanium particles. METHODS: We assessed peri-implantitis cases defined according to established definitions from a cross-sectional study that had implants in function for at least 2 y. Controls were sampled from the same population and had healthy implants. Peri-implant crevicular fluid samples were collected and prepared for immunohistochemical analysis of 5-methylcytosine (5mC), and submucosal plaque samples were collected and subjected to inductively coupled plasma mass spectrometry (ICP-MS) for measuring titanium. Data were analyzed via generalized estimating equation models to account for multiple implants per participant. RESULTS: Forty participants were included; 21 implants with peri-implantitis and 24 healthy implants were included in the analysis. Epigenetic alterations in global gene methylation were significantly more pronounced in peri-implantitis cases as compared to controls (P = 0.002). Adjustment for smoking status further strengthened the association (P = 0.0079). Higher adjusted titanium quantities had significantly higher 5mC (P < 0.001). CONCLUSIONS: Peri-implantitis cases exhibited increased levels of methylated DNA cytosine (5mC) as compared to controls, suggesting that peri-implantitis is associated with epigenetic alterations in the peri-implant tissues. In addition, the finding that titanium concentrations were associated with global methylation levels independent of peri-implantitis status suggests that methylation may be affected by titanium dissolution products. Collectively, these results support further investigations to determine if these associations are causal or ecological in nature. KNOWLEDGE TRANSFER STATEMENT: These are the first human data to elucidate the epigenetic regulation of gene transcription via hypermethylation as a potential mechanism involved in peri-implantitis. Furthermore, they identify titanium dissolution products as a potential environmental factor associated with this hypermethylation, which provides cues for novel therapeutic targets for peri-implantitis.

The survival of indirect composite resin onlays for the restoration of root filled teeth: a retrospective medium-term study.

AIM: To investigate the outcomes of root filled posterior teeth restored with indirect composite resin onlays using tooth and restoration survival as well as the quality of restoration as outcome measures. METHODOLOGY: All patients were treated by the same clinician with indirect composite onlays for the restoration of root filled posterior teeth between January 2008 and February 2010 in a single clinic setting. Primary root canal treatment was performed and onlays fabricated with the indirect method using indirect composite resin. Patients were seen every 4-6 months for maintenance visits according to standard clinic protocols and each patient's individualized maintenance schedule. Tooth and restoration survival were calculated, and the onlays were evaluated in accordance with the modified US Public Health Service (USPHS) criteria. RESULTS: Thirty-one premolars and one hundred and fifty-eight molars (n = 189) of 153 patients were included. The observation period ranged from 24 to 52 months with a median follow-up time of 37 months. Tooth survival was found to be 100%, whilst the restoration survival was 96.8% and the functional restoration survival 98.9% at the end of the follow-up period. According to modified USPHS criteria, the A rating had a range of 83.1-100% for all evaluation criteria. CONCLUSIONS: Onlay restorations fabricated with indirect resin can be a viable option for the restoration of root filled teeth.