OBJECTIVE: Peri-implant diseases, being the most common implant-related complications, significantly impact the normal functioning and longevity of implants. Experimental models play a crucial role in discovering potential therapeutic approaches and elucidating the mechanisms of disease progression in peri-implant diseases. This narrative review comprehensively examines animal models and common modeling methods employed in peri-implant disease research and innovatively summarizes the in vitro models of peri-implant diseases.
METHODS: Articles published between 2015 and 2023 were retrieved from PubMed/Medline, Web of Science, and Embase. All studies focusing on experimental models of peri-implant diseases were included and carefully evaluated.
RESULTS: Various experimental models of peri-implantitis have different applications and advantages. The dog model is currently the most widely utilized animal model in peri-implant disease research, while rodent models have unique advantages in gene knockout and systemic disease induction. In vitro models of peri-implant diseases are also continuously evolving to meet different experimental purposes.
CONCLUSIONS: The utilization of experimental models helps simplify experiments, save time and resources, and promote advances in peri-implant disease research. Animal models have been proven valuable in the early stages of drug development, while technological advancements have brought about more predictive and relevant in vitro models.
CONCLUSIONS: This review provides clear and comprehensive model selection strategies for researchers in the field of peri-implant diseases, thereby enhancing understanding of disease pathogenesis and providing possibilities for developing new treatment strategies.

OBJECTIVE: To evaluate the efficacy of minocycline hydrochloride combined with metronidazole versus metronidazole alone in treating peri-implantitis and their impact on specific inflammatory markers.
METHODS: A retrospective review was undertaken of 107 patients with peri-implantitis from January 2018 to January 2021. Patients were treated either with metronidazole alone (Con group, n = 57) or with additional minocycline hydrochloride (Exp group, n = 50). Inflammatory markers, including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and matrix metalloproteinase-8 (MMP-8) were determined before and after treatment. Clinical outcomes were determined using the plaque index (PLI), gingival sulcus bleeding index (SBI), and periodontal probing depth (PD). Furthermore, receiver operator characteristic (ROC) curves analyzed the clinical relevance of the markers. Logistic regression was conducted to analyze the risk factors affecting efficacy in patients.
RESULTS: The Exp group exhibited more favorable clinical outcomes and showed lower levels of IL-6, IL-1β, TNF-α, and MMP-8 than the Con group. IL-1β, TNF-α, and MMP-8 levels were significantly correlated with treatment success (P < 0.05), but IL-6 was not (P > 0.05). The ROC curves for IL-1β and TNF-α significantly outperformed those for IL-6 and MMP-8 (P < 0.05). Logistic regression analysis showed that only IL-1β and TNF-α were independent risk factors affecting efficacy in patients.
CONCLUSIONS: Combining minocycline hydrochloride with metronidazole yields better outcomes for peri-implantitis compared to metronidazole alone. Of the factors analyzed, only IL-1β and TNF-α emerged as dependable independent efficacy indicators.

UNASSIGNED: Dental implants have become an increasingly popular option for replacing missing teeth, and the prevalence of peri-implantitis has also increased, which is expected to become a public health problem worldwide and cause high economic and health burdens. This scenario highlights the need for new therapeutic options to treat peri-implantitis.
UNASSIGNED: In this study, we proposed a novel sono-responsive antibacterial nanosystem co-loaded with metformin (Met) and bone morphogenetic protein-2 (BMP-2) to promote efficacy in treating peri-implantitis. We introduced the zeolitic imidazolate framework-8 (ZIF-8) as a carrier for hematoporphyrin monomethyl ether (HMME) to enhance the antibacterial effect of sonodynamic antibacterial therapy and tested its reactive oxygen species (ROS) production efficiency and bactericidal effect in vitro. Afterward, HMME-loaded ZIF-8, BMP-2-loaded polylactic acid-glycolic acid (PLGA), and Met were incorporated into gelatin methacryloyl (GelMA) hydrogels to form HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels, and the biocompatibility of which was determined in vitro and in vivo. A bacterial-induced peri-implantitis model in the maxilla of rats was established to detect the effects of the composite hydrogels with adjunctive use of ultrasound on regulating inflammation and promoting bone tissue repair in vivo.
UNASSIGNED: The results indicated that HMME@ZIF-8 with ultrasound stimulation demonstrated more better ROS production efficiency and antimicrobial efficacy. The composite hydrogels had good biocompatibility. Ultrasound-assisted application of the composite hydrogels reduced the release of the inflammatory factors IL-6 and TNF-α and reduced bone loss around the implant in rats with bacterial-induced peri-implantitis.
UNASSIGNED: Our observations suggest that HMME@ZIF-8 may be a new good sonosensitizer material for sonodynamic antibacterial therapy. The use of HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels in combination with ultrasound can provide a novel option for treating peri-implantitis in the future.

暂无摘要。

BACKGROUND: Peri-implantitis and periodontitis have similar immunological bioprocesses and inflammatory phenotypes. In the inflammatory process, the adaptive immune cells can drive the development of disease. This research investigated the differences and diagnostic significance of peri-implantitis and periodontitis in adaptive immune responses.
METHODS: We acquired four GEO datasets of gene expressions in surrounding tissues in healthy person, healthy implant, periodontitis, and peri-implantitis patients. The structural characteristics and enrichment analyses of differential expression genes were examined. The adaptive immune landscapes in peri-implantitis and periodontitis were then evaluated using single sample gene set enrichment analysis. The STRING database and Cytoscape were used to identify adaptive hub genes, and the ROC curve was used to verify them. Finally, qRT-PCR method was used to verify the expression level of Hub gene in activated T cells on the titanium-containing or titanium-free culture plates.
RESULTS: At the transcriptome level, the data of healthy implant, peri-implantitis and periodontitis were highly dissimilar. The peri-implantitis and periodontitis both exhibited adaptive immune response. Except for the activated CD4+T cells, there was no significant difference in other adaptive immune cells between peri-implantitis and periodontitis. In addition, correlation analysis showed that CD53, CYBB, and PLEK were significantly positively linked with activated CD4+T cells in the immune microenvironment of peri-implantitis, making them effective biomarkers to differentiate it from periodontitis.
CONCLUSIONS: Peri-implantitis has a uniquely immunogenomic landscape that differs from periodontitis. This study provides new insights and ideas into the activated CD4+T cells and hub genes that underpin the immunological bioprocess of peri-implantitis.

The purpose of the study is to investigate the relationship of peri-implantitis (PI) with FCGR2A and FCGR3A gene polymorphisms. One hundred and forty-four patients with PI and 136 patients without PI infection were selected. Gingival crevicular fluid samples were collected from the two groups. The FCGR2A and FCGR3A polymorphism in the two groups were measured. All volunteers were evaluated for periodontal status. The effect of polymorphisms on PI susceptibility was investigated by chi-square analysis and logistic regression. The frequency of FCGR2A rs1801274 GG genotype of PI group was higher than that of the control group, while the GA and AA genotype carriers were less in PI group. After adjusting for other clinical indicators, rs1801274 GA genotype, AA genotype, and the A allele were still negatively correlated with the onset of PI. FCGR3A rs396991 polymorphism was not associated with PI. FCGR2A rs1801274 polymorphism was significantly associated with PI in the Chinese Han population, and GG genotype might be a genetic risk factor for PI.

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.

To analyze the role of oxidative stress (OS) biomarkers in peri‑implant diseases using a systematic review and meta-analysis approach. DATE: The review incorporated cross-sectional studies, randomized controlled trials, and case-control trials to evaluate the differences in OS biomarkers of peri‑implant disease.
A comprehensive literature search was conducted in electronic databases such as PubMed, Scopus, Embase, Web of Science, and CNKI, and no restrictions were applied during the search process.
A total of 452 studies were identified, of which 18 were eligible for inclusion. Risk of bias and sensitivity analysis were assessed using Egger\'s test and funnel plots.
We found that the levels of glutathione peroxidase (GSH-Px) in the peri‑implant sulcus fluid (PISF) of patients with peri‑implant diseases were significantly reduced (SMD = -1.40; 95 % CI = 1.70, -1.11; p < 0.001), while the levels of total myeloperoxidase (MPO) and malondialdehyde (MDA) were significantly increased (SMD = 0.46; 95 % CI = 0.12, 0.80; p = 0.008; SMD = 0.28; 95 % CI = 0.01, 0.56; p = 0.043). However, there were no significant differences of MPO concentration (SMD = 0.38; 95 % CI = -0.39, 1.15; p = 0.331) and superoxide dismutase (SOD)(SMD = -0.43; 95 % CI = -1.94, 1.07; p = 0.572) in PISF between peri‑implant disease group and control group. Similarly, salivary MPO did not show significant differences (SMD = 1.62; 95 % CI = -1.01, 4.24; p = 0.227).
Our results supported that the level of local OS biomarkers was closely related to peri‑implant diseases. GSH-Px, total MPO and MDA may be PISF biomarkers with good capability to monitor the development of peri‑implant disease.
This study found significant differences in the levels of local OS biomarkers (GSH-Px, total MPO, and MDA) between patients with peri‑implant diseases and healthy subjects, which may be ideal candidate biomarkers for predicting and diagnosing peri‑implant diseases.

Early diagnosis of peri-implantitis (PI) is crucial to understand its pathological progression and prevention. This study is committed to investigating the signature genes, relevant signaling pathways and their associations with immune cells in PI. We analyzed differentially expressed genes (DEGs) from a PI dataset in the gene expression omnibus database. Functional enrichment analysis was conducted for these DEGs. Weighted Gene Co-expression Network Analysis was used to identify specific modules. Least absolute shrinkage and selection operator and support vector machine recursive feature elimination were ultimately applied to identify the signature genes. These genes were subsequently validated in an external dataset. And the immune cells infiltration was classified using CIBERSORT. A total of 180 DEGs were screened from GSE33774. Weighted Gene Co-expression Network Analysis revealed a significant association between the MEturquoise module and PI (cor = 0.6, P < .0001). Least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms were applied to select the signature genes, containing myeloid-epithelial-reproductive tyrosine kinase, microfibrillar-associated protein 5, membrane-spanning 4A 4A, tribbles homolog 1. In the validation on the external dataset GSE106090, all these genes achieved area under curve values exceeding 0.95. GSEA analysis showed that these genes were correlated with the NOD-like receptor signaling pathway, metabolism of xenobiotics by cytochrome P450, and arachidonic acid metabolism. CIBERSORT revealed elevated levels of macrophage M2 and activated mast cells in PI. This study provides novel insights into understanding the molecular mechanisms of PI and contributes to advancements in its early diagnosis and prevention.

Objective: To evaluate the correlation between peri-implant probing depth (PPD) and radiographic bone level (rBL) in implants with peri-implantitis. Methods: From January 2019 to December 2022, 24 patients with 30 implants who suffered from peri-implantitis at the Department of Periodontology, Peking University School and Hospital of Stomatology were included in the present research. SPSS 26.0 software was used to simple random sampling select 30 healthy implants from which with electronic examination records in Department of Periodontology, Peking University School and Hospital of Stomatology from January 2007 to June 2023 as the control group. On the premise of retaining the implant prosthesis, PPD (distance between pocket bottom and peri-implant soft tissue margin) was examined using a Williams periodontal probe with a light force (about 0.2 N), and a total of 4 sites were recorded for each implant. Periapical radiography and cone beam CT were applied to measure the rBL (distance between the reference point at the neck of the implant and the apical point of the bone defect) and the width of the bone defect (DW), and the type of the bone defect was recorded. The correlation and consistency between the diagnosis of PPD and rBL were analyzed. Results: PPD was significantly correlated with rBL in a total of 60 implants in 180 sites (r=0.64, P<0.001). The chi-square test showed an 8.15-fold increase in the detection rate of PD≥6 mm at sites with rBL≥1 mm (P<0.001). Multivariate logistic regression analysis showed that rBL was still statistically associated with PPD after adjustment for jaw position and examination position of implants. Take rBL <1 mm as reference, the odds ratios (OR) of 1 mm≤rBL<2 mm, 2 mm≤rBL<3 mm and rBL≥3 mm group with PPD were 6.23 (P=0.014), 2.77 (P=0.183) and 10.87 (P=0.001), respectively. Conclusions: There is a positive correlation between PPD and rBL in implants with peri-implantitis. PPD can be used as a clinical examination index to assist in estimating the level of peri-implant bone under the premise of retaining the prosthesis.
目的： 探讨种植体周炎患者种植体周探诊深度（PPD）与影像学骨水平（rBL）的相关性。 方法： 纳入2019年1月至2022年12月于北京大学口腔医学院·口腔医院牙周科就诊的种植体周炎患者24例，涉及患病种植体30枚，另从2007 年1月至2023年6月在北京大学口腔医学院·口腔医院牙周科有电子检查记录的种植体中，使用SPSS26.0软件进行简单随机抽样选取30枚健康种植体作为对照。在保留种植修复体的前提下，使用Williams牙周探针以轻力（约0.2 N）测量PPD（种植体袋底到黏膜边缘的距离），记录各种植体颊侧、舌侧、近中及远中共4个位点的PPD。应用根尖片测量健康种植体近远中影像学骨水平（rBL，种植体颈部参考点与骨缺损最根方位点之间的距离），应用根尖片和锥形束CT分别测量种植体周炎种植体近远中及颊舌侧rBL及骨缺损宽度（DW），并记录骨缺损类型。应用χ2检验、Spearman检验和Logistic回归分析PPD与rBL的相关性及临床探诊诊断与影像学诊断的一致性。 结果： 30枚健康种植体的近中、远中共60个位点和30枚种植体周炎种植体近中、远中、颊侧、舌侧共120个位点，共计180个位点的PPD与rBL显著正相关（r=0.64，P<0.001）。χ2检验显示种植体周炎种植体中，rBL≥1 mm与PD≥6 mm显著相关［优势比（OR）=8.15，P<0.001］。多因素Logistic回归分析显示，在校正种植体颌位和检查位置后，rBL与PPD仍然存在统计学关联，以rBL<1 mm为参照，rBL≥1 mm且<2 mm组、rBL≥2 mm且<3 mm组及rBL≥3 mm组与PPD间的OR值分别为6.23（P=0.014）、2.77（P=0.183）和10.87（P=0.001）。 结论： 种植体周炎种植体的PPD与 rBL呈显著正相关，在保留修复体的前提下，PPD可作为辅助判断种植体周骨水平的临床检查指标。.