Yung‐Ting Hsu

Background: This scoping review evaluates the recovery pattern of host responses, in terms of immune regulation and tissue remodeling, in gingival crevicular fluid (GCF) during experimental gingivitis (EG) resolution phase. Methods: Electronic database and hand searches were conducted to screen the literature published from January 1960 to December 2024. The selected studies were randomized and non‐randomized controlled trials evaluating the changes of clinical parameters and host responses in GCF mediators during EG, focusing on the baseline and the resolution phase. Due to the heterogeneity of the included studies, a meta‐analysis was not conducted. Evidence quality and risk of bias were assessed. Results: A total of 17 studies with 303 volunteers met the inclusion criteria, analyzing four clinical parameters and 58 biomarkers in GCF samples. Pro‐inflammatory cytokines and mediators associated with tissue remodeling, such as IL‐1α, IL‐1β, MMP‐8, and ALP increased during EG induction and decreased during EG resolution, similar to the trends in the clinical parameters. In contrast, the levels of MIP‐1β and IL‐10 were reduced during EG induction and elevated during EG resolution. In addition, the levels of IL‐1β and ALP were able to return to baseline level at the end of the resolution phase. Conclusions: This scoping review showed that, following an average EG resolution period of 7 to 21 days, clinical signs of inflammation improved or restored. Notably, IL‐1β and ALP exhibited a return of levels to their pre‐disease (baseline) state, suggesting their potential as indicators for monitoring dynamic changes in inflammatory status at the molecular level during EG resolution.

Background: This review aims to evaluate dimensional changes in the alveolar ridge and complications following ridge augmentation using tunnelling techniques. Methods: An electronic search was conducted in PubMed , Embase , and Web of Science to identify randomized and non-randomized prospective studies and retrospective human case-control or cohort studies comparing the efficacy of ridge augmentation using tunneling techniques during 1st January 1980 to 31st December, 2025. Two calibrated independent reviewers assessed the selected studies. The main outcome measured was the horizontal bone gain (HBG) and vertical bone gain (VBG) evaluated from the initial baseline visit to the final follow-up. Meta-analysis was performed to analyze HBG and VBG and their differences between the test group (undergoing tunneling ridge augmentation) and controls (ridge augmentation via flapped approaches). Meta-regression was performed to investigate the contributing factors of these outcomes. Results: Eleven studies enrolling 491 patients were selected in this review. The pooled HBG and VBG were 4.58 mm (95% Confidence Interval (CI) [2.61,6.54], p < 0.01) and 4.86 mm (CI [3.53,6.20], p < 0.01), respectively. Compared to the control group, the HBG was not significantly different between the two groups (0.65 mm, CI [-0.01,1.31], p = 0.05). In contrast, the test group had significantly greater VBG than the control group (0.70 mm, CI [0.26,1.14], p < 0.01). Most of the reported complications were temporary and mild. However, a few cases involved serious complications, such as nerve injury and graft failure. Conclusion: Tunneling techniques appear to be a feasible approach for horizontal and vertical ridge augmentation. Evidence remains insufficient to determine whether tunneling techniques increase bone gain or reduce complications compared with conventional flapped approaches.

Aim: This study compared host responses against natural gingivitis in the gingival crevicular fluid (GCF) in young and aged periodontium. Materials and methods: This cross-sectional study recruited two patient populations with natural gingivitis in young (18–35 years old) and elder cohorts (36–75 years old). GCF samples were analyzed for 39 inflammatory and tissue remodeling mediators using bead-based multiplex immunoassays. Independent t-tests with false discovery rate adjustments were used to compare mediator expressions between groups. Results: Forty patients were enrolled in these comparisons, including young patients (n=22) and elder patients (n=18). In comparison with the young group, the elder group had greater clinical attachment loss and higher expression of MPO (p<0.001), IL-1β (p<0.05), IL-6 (p<0.05), and IL-8 (p0.05), the young group had greater ratio of MMP-9/TIMP-1 than old group (p<0.01). Conclusion: The current findings reveal that the inflammatory profiles of young and elder cohorts with natural gingivitis are distinct. The young cohort with natural gingivitis demonstrated lower disease susceptibility and more robust tissue turnover, whereas the aged periodontium was characterized by higher susceptibility to disease and diminished healing capacity.

Introduction: Individual variability determines host responses and disease progression. Inflammatory clusters (ICs) have been shown to influence host responses against bacterial challenges during the induction of human experimental gingivitis. Objectives: This study aimed to evaluate the role of ICs in naturally occurring gingivitis and periodontitis. Methods: Using a cross-sectional and split-mouth design, this study evaluated the immune regulation and tissue-remolding responses in sites with different disease severity of periodontal diseases to provide a comprehensive assessment of disease features on the basis of analyzing gingival crevicular fluids. Cluster analysis was performed based on the clinical indices, including gingival index, plaque index, and probing depth. Further comparisons of the host mediators and clinical indices among clusters based on the disease severity were also performed. Results: A total of 48 patients were recruited in this study, including 24 patients with gingivitis only and 24 patients with stage III grade B generalized periodontitis. Our results demonstrate that 2 distinct ICs were found in the sites with naturally occurring gingivitis: low-ICs had less expression of myeloperoxidase, intercellular adhesion molecule–1, and interleukin-12 as well as greater expression of angiopoietin-1 than high-ICs did. At the sites with generalized severe periodontitis, however, low-ICs had significantly elevated expression of angiopoietin-1, fractalkine, granulocyte-macrophage colony-stimulating factor, matrix metalloproteinase-2, osteopontin, and vascular endothelial growth factor versus high-ICs. Our results for the first time confirmed the influence of ICs in naturally occurring gingivitis, showing that low-ICs displayed minimal inflammation and less neutrophil involvement compared with high-ICs. The influence of ICs in periodontitis was site specific rather than patient specific. Conclusion: Our collective findings highlight the importance of ICs in disease progression, benefiting the modulation of immune responses and preventing further periodontal tissue destruction. By identifying specific ICs, clinicians can better predict disease progression and recurrence, ultimately improving patient outcomes through targeted interventions. Knowledge Transfer Statement: The present study discovered the role of inflammatory clusters (ICs) on the host responses in a cross-sectional setting, including immune regulation and tissue remodeling, during naturally occurring gingivitis, whereas the disease progression to periodontitis seems to be site specific. Low-ICs were more prevalent in the gingivitis-only group compared with the periodontitis group, suggesting that gingivitis sites in periodontitis patients may be at increased risk for disease progression compared with gingivitis sites in gingivitis-only patients

Aim: This study aims to validate an existing risk assessment (RA) tool for predicting sinus membrane perforation (SMP) during the lateral‐window sinus floor elevation (LSFE). Materials and Methods: A multiple‐center study was conducted in a hospital and university setting. Cone‐beam computed tomography (CBCT) images and health records of patients who received LSFE from 2005 to 2021 were assessed. The effectiveness of the RA tool was evaluated on our dataset and additional analyses were performed to identify the key risk factors using logistic regression and the classification and regression trees (CART) methods. Results: A total of 126 sinuses in 113 patients were assessed, including 49 females and 64 males (60.1 ± 11.65 y/o). There were 24 SMP events in the study population. Patient‐level and sinus‐level analyses were consistent. The reduced logistic regression model suggested that the odds ratio (OR) of having an SMP event decreases by 23.7% with a 1 mm increase in residual bone height (RBH). Using a 3‐mm RBH as the cut‐off between “low risk” and “high risk,” rather than 4 mm as suggested in the original RA tool, provided better separation of SMP rates. CART analysis revealed that age may also be related to SMP risk. Conclusion: In this exploratory study, RBH was the factor most correlated with SMP risk during LSFE, followed by age at the time of surgery. The critical thresholds for predicting SMP events were identified as 3.02 mm for RBH and 55.5 years of age. Within the inherent limitations, the current risk assessment tool could not be fully validated.

Background: This systematic review summarized the features of human experimental gingivitis (EG) in terms of immune responses and tissue remodeling in the gingival crevicular fluid (GCF). Methods: Systematic searches were conducted to screen the literature published from January 1960 to June 2024 from MEDLINE (PubMed), EMBASE, and Web of Science. The selected studies were prospective trials evaluating the immune responses and tissue remodeling mediators in GCF before and after EG via oral hygiene refrain. Evidence quality and risk of bias were assessed. Results: Thirty studies with 594 volunteers met the inclusion criteria, analyzing 74 clinical parameters and biomarkers in GCF samples. Consistent with EG induction, the EG sites showed an increase in plaque index (PI), gingival index (GI), and myeloperoxidase (MPO) (an indicator of neutrophil migration). In addition, the expression levels of interleukin (IL)‐1α and IL‐1β were increased, also consistent with the previous literature investigating active lesions of periodontal inflammation during gingivitis. However, the expression of macrophage inflammatory protein (MIP)‐1 β, monocyte chemoattractant protein (MCP)‐1, CCL2, and fractalkine/CX3CL1 decreased among EG in multiple studies demonstrating an EG effect on recruitment and cellular communication of mononuclear cells. In contrast, the levels of fibroblast growth factors (FGFs), vascular endothelial growth factor (VEGF), and anti‐inflammatory cytokines showed insignificant changes during EG induction. Aging, stress level, and the diabetes status of the volunteer populations affected the outcomes. Conclusions: The features of acute inflammatory lesions of EG with limited tissue destruction showcase that it is a valuable tool to investigate the initial immune responses on gingival tissue against bacterial challenges. Plain Language Summary: This review examined how human experimental gingivitis (EG) affects immune responses and tissue changes in the fluid around the gums. Researchers analyzed studies published from 1960 to 2024, focusing on those that looked at immune responses and tissue changes in gum fluid before and after participants stopped brushing their teeth to induce EG. The review included 30 studies with 594 participants, exploring various health markers in gum fluid. When EG was induced, areas of the gums showed increased plaque and markers of inflammation, indicating an inflammatory response. Specifically, two inflammatory proteins (interleukin [IL]‐1α and IL‐1β) were found in greater expression, which aligns with what previous research has shown in gum disease. However, levels of certain proteins that help attract monocytes and macrophages decreased, suggesting changes in how these cells communicate during EG. Additionally, the levels of growth factors and anti‐inflammatory substances did not change significantly. Factors such as age, stress, and diabetes also influenced the outcomes. These findings help us understand early immune responses in gum disease, which is crucial for developing prevention strategies and improving oral health overall.

Background: The aim of this study is to evaluate the immune regulation and tissue remodeling responses during experimental gingivitis (EG) and naturally occurring gingivitis (NG) to provide a comprehensive analysis of host responses. Gingival crevicular fluid (GCF) was obtained from 2 human studies conducted in university settings.Methods: The EG study enrolling 26 volunteers provided controls for the baseline (Day 0) from healthy disease‐free participants, while Day 21 (the end of EG induction of the same group) was used to represent EG. Twenty‐six NG participants age‐matched with those of the EG group were recruited. GCF samples were analyzed for 39 mediators of inflammatory/immune responses and tissue remodeling using commercially available bead‐based multiplex immunoassays. The differences in GI and mediator expression among groups were determined at a 95% confidence level (p ≤ 0.05) by a 2‐way analysis of variance (ANOVA) with a post‐hoc Tukey's test.Results: Our findings showed that EG had a greater gingival index than NG and was healthy (p < 0.01 of all comparisons). Furthermore, EG showed significantly higher levels of MPO (p < 0.001), CCL3 (p < 0.05), and IL‐1B (p < 0.001) than NG. In contrast, NG had increased levels of MIF (p < 0.05), Fractalkine (p < 0.001), angiogenin (p < 0.05), C3a (p < 0.001), BMP‐2 (p < 0.001), OPN (p < 0.05), RANKL (p < 0.001), and MMP‐13 (p < 0.001) than EG.Conclusions: Consistent with the findings from chronic (NG) versus acute (EG) inflammatory lesions, these data reveal that NG displays greater immune regulation, angiogenesis, and bone remodeling compared to EG.

INPLASY2023120050 Immune regulation and tissue remodeling mediators of EG: systematic review Keywords: experimental gingivitis, tissue remodeling, immune regulation. Download PDF – 2023120050…