pdgfbb与vegfa与种植体黏膜炎

OBJECTIVES To clinically and histologically evaluate the efficacy of using acellular dermal matrix (ADM) for peri-implant vertical soft tissue augmentation at implant placement. MATERIALS AND METHODS Twenty patients were enrolled in this study. According to the initial thickness of vertical soft tissue, patients were assigned into the ADM group (≤2 mm) or the control group (>2 mm) prior to implant surgery + ADM grafting or implant surgery alone. Second-stage surgery was carried out 3 months later and a small piece of ridge membrane was harvested for histological and immunohistochemical evaluation. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in peri-implant crevicular fluid (PICF) were also assessed 1 week, 1 month and 5 months after second-stage surgery. Clinical parameters were recorded to evaluate peri-implant health at 1 week and 3 months after implant restoration. RESULTS All 20 implants healed uneventfully and successfully. Soft tissue thicknesses were comparable in the two groups at second-stage surgery (3.20 ± 0.42 mm vs 3.50 ± 0.58 mm). In the ADM group, the mean increase in soft tissue thickness was 1.85 ± 0.34 mm. Histological and immunohistochemical outcomes showed no differences between the two groups. VEGF and PDGF-BB levels in PICF were significantly lower in the ADM group 1 week after second-stage surgery (p < 0.01), yet they decreased in both groups later. The difference between the groups had disappeared by 5 months after second-stage surgery. The clinical peri-implant parameters were good and stable by the end of the study (3 months after restoration). CONCLUSIONS Our results suggested that using ADM at implant placement was effective in increasing the thickness of peri-implant vertical soft tissue and achieved comparable clinical and histological performance to the control group. However, the incremental soft tissue showed inferior angiogenic ability in the early stage of wound healing.

Dental implants are very successful medical devices, yet implant failures do occur due to biological and mechanical complications. Peri‐implantitis is one such biological complication that is primarily caused by bacteria and their products at the implant soft tissue interface. Bacterial infiltration can be prevented by the formation of a reliable soft tissue seal encircling dental implants. Platelet‐derived growth factor‐BB (PDGF‐BB) has significant chemotactic and proliferative effects on various mesenchymal cell types, including fibroblasts, and therefore can be an effective molecule to enhance the peri‐implant soft tissue seal. To overcome the limitations of the recombinant protein form of PDGF‐BB, such as cost and the need for supraphysiological doses, we have developed and characterized a titanium surface that is rendered bioactive by coating it with polyethylenimine‐plasmid DNA (pDNA) nanoplexes in the presence of sucrose. Human embryonic kidney 293T (HEK293T) cells and human primary gingival fibroblasts (GFs) were successfully transfected in culture with enhanced green fluorescent protein (EGFP)‐encoding pDNA or platelet‐derived growth factor subunit B (PDGFB)‐encoding pDNA loaded into nanoplexes and coated onto titanium disks in a dose‐dependent manner. GFs were shown to secrete PDGF‐BB for at least 7 days after transfection and displayed both minimal viability loss and increased integrin‐α2 expression 4 days posttransfection.

Abstract Aim The aim of this study is to assess early wound healing expression of local angiogenic biomarkers following connective tissue graft (CTG) at dental implant sites. Methods Twenty‐eight subjects with single dental implants exhibiting a soft tissue dehiscence were included and randomly treated with CTG, either with coronally advanced flap (CAF) or with tunnel technique (TUN). Peri‐implant crevicular fluid (PICF) was collected at the midfacial and midlingual aspect of the implant sites at baseline and at 3, 7, 14, 30, and 90 days after the surgical intervention. The expression of angiogenin (ANG), fibroblast growth factor‐2 (FGF‐2), platelet‐derived growth factor (PDGF), tissue inhibitor of metalloproteinases‐2 (TIMP‐2), and vascular endothelial growth factor (VEGF) was investigated over a period of 3 months. Patient‐reported outcomes, clinical measurements, and ultrasonography scans at multiple time points were also evaluated. Results The longitudinal regression revealed a significant difference in the expression of VEGF and TIMP‐2 between CAF‐ and TUN‐treated sites over 3 months (p = .033 and p = .004, respectively), whereas no significant differences were observed for ANG, FGF‐2 and PDGF between the two groups. At 7 days, a direct correlation was observed between ANG levels and ultrasonographic color velocity in the CAF group (p < .001) and between ANG levels and ultrasonographic color power in the TUN group (p = .028). VEGF levels and ultrasonographic mean perfused area of the CTG were significantly correlated at the 7‐day time point (p < .001 for both CAF and TUN). The expression of VEGF at 7 days was directly associated with mucosal thickness gain at 1 year (p < .001 for both groups). Early TIMP‐2 expression showed an inverse correlation with time to recovery (p = .002). TIMP‐2 levels at 3 months exhibited inverse correlations with mean dehiscence coverage (p = .004) and the rate of complete dehiscence coverage (p = .012). Conclusion PICF biomarkers can be used to monitor early wound healing events following soft tissue grafting at implant sites. VEGF and TIMP‐2 showed correlations with the 1‐year clinical and volumetric outcomes, as well as with post‐operative patient‐reported outcomes and Doppler Ultrasonographic tissue perfusion‐related parameters.

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BACKGROUND Peri-implant mucositis (PIM) is a pathological precursor of peri-implantitis, but its pattern of conversion to peri-implantitis is unclear and complicated to diagnose clinically, while none of the available protocols yield complete disease resolution. The aim of this study was the evaluation of PIM responsiveness to standard anti-infective mechanical treatment (AIMT) at clinical and biomarker levels, and estimation of the diagnostic capacity of bone markers as surrogate endpoints and predictors. METHODS Systemically healthy outpatients presenting one implant exhibiting clinical signs of inflammation confined within the soft tissue (PIM) and one healthy control (HC) implant at a non-adjacent position were included. Clinical parameters and peri-implant crevicular fluid samples were collected baseline and 6 months following mechanical therapy, to assess the levels of RANKL, OPG, and IGFBP2. PIM clustering was performed using machine learning algorithms. RESULTS Overall, 38 patients met the inclusion criteria. Therapy resulted in the reduction of all clinical and biological indicators, but respective values remained significantly higher compared to HC. Clinical examination noted 30% disease resolution at the 6-month follow-up, while 43% showed no active bone resorption. OPG showed positive prognostic value for treatment outcome, while the clustering based on active bone resorption did not differ in terms of therapeutic effectiveness. CONCLUSION AIMT is effective in reducing the clinical and biological indicators of PIM, but complete clinical resolution was achieved in only 30% of the cases. Around one third of PIM patients exhibited active bone resorption bellow clinical detectability that was not associated with disease progression and poor treatment responsiveness.

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Introduction: Modern dentistry aims to restore the comfort and health of the stomatognathic system. Dental implants have emerged as a promising option for this purpose. Concentrated growth factors (CGFs) have been suggested to enhance the healing of bone grafts and enhance the integration of implants into the bone. Growth factors are proteins which regulate the complex process of wound healing. They play an important role in cell migration, cell proliferation, and angiogenesis in the tissue regeneration phase. CGF was first developed by Sacco in 2006. It can be used as a barrier membrane to accelerate soft-tissue healing. CGF does not require any chemical or anticoagulants, and hence, it is free from viral transmission diseases. Crestal bone levels, peri-implant bone density, bleeding, probing depth, mobility, occlusion factors, restoration adequacy, radiographic images, oral hygiene, and patient health status are some of the important parameters for determining longevity of success rates in implant dentistry. This study will assess the peri-implant bone density and crestal bone levels with and without the use of CGF. Aim: To evaluate the effect of CGFs on peri-implant bone density and in the preservation of crestal bone levels around dental implants. Materials and Methods: Sampling procedure: Random selection of population (Sealed envelope method) Number of groups: Two-Control group (Group 1) and Experimental group (Group 2) Sample size: 20 For Group 2, implants were placed with CGF. For Group 1, implants were placed without CGF. The peri-implant bone density and bone levels were measured by Digora and signora software. Results: The mean crestal bone loss on the mesial aspect of implants placed in Group 2 is 0.294 mm and Group 1 is 0.345 mm, and the mean crestal bone loss on the distal aspect of implants placed in Group 2 is 0.320 mm and in Group 1 is 0.331 mm. There are no many significant differences on mesial and distal aspects around implants between the two groups Intragroup comparison of bone density values in Group 1 shows the mean difference from baseline to 1 month is 0.6, and after three and 6 months periods are 1.1 and 1.1, respectively, which indicates not much significant improvement in bone density values in Group 1. Intergroup comparison shows a significant difference between both the groups starting from as early as the 1st month. Conclusion: The results of this study indicate that CGF is significantly better in the regeneration of bone around the implants when comparing with nonCGF groups. Although CGF showed improvement in bone formation, there are no many differences in crestal bone level changes on mesial and distal sides of the implants between the two groups.

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OBJECTIVES VEGF is prototypic marker of neovascularization, repeatedly proposed as intrinsic characteristic of peri-implantitis. This study aimed to assess pattern of VEGF in peri-implantitis, its correlation with titanium particles (TPs) and capacity as respective biomarker. MATERIAL AND METHODS Pathological specificity of VEGF was assessed in peri-implant granulations using immunohistochemistry, periodontal granulations represented Ti-free positive controls. VEGF was correlated to TPs, identified using scanning electron microscopy coupled with dispersive x-ray spectrometry. Diagnostic accuracy, sensitivity and specificity of VEGF were estimated in PICF specimens from peri-implantitis, peri-implant mucositis (PIM) and healthy peri-implant tissues (HI) using machine learning algorithms. RESULTS Peri-implantitis exhibited rich neovascular network with expressed density in contact zones toward neutrophil infiltrates without specific pattern variations around TPs, identified in all peri-implantitis specimens (mean particle size 8.9 ± 24.8 µm2; Ti-mass (%) 0.380 ± 0.163). VEGF was significantly more expressed in peri-implantitis (47,065 ± 24.2) compared to periodontitis (31,14 ± 9.15), and positively correlated with its soluble concentrations in PICF (p = 0.01). VEGF was positively correlated to all clinical endpoints and significantly increased in peri-implantitis compared to both PIM and HI, but despite high specificity (96%), its overall diagnostic capacity was average. Two patient clusters were identified in peri-implantitis, one with 8-fold higher VEGF values compared to HI, and second with lower values comparable to PIM. SIGNIFICANCE VEGF accurately reflects neovascularization in peri-implantitis that was expressed in contact zones toward implant surface without specific histopathological patter variation around TPs. VEGF answered requests for biomarker of peri-implantitis but further research is necessary to decrypt its exact underlying cause.

Abstract Zirconia abutments and restorations have improved the aesthetic appeal of implant restoration, yet peri-implantitis poses a significant threat to long-term success. The soft tissue surrounding implants is a crucial biological barrier against inflammation and subsequent bone loss. Peri-implantitis, akin to periodontitis, progresses rapidly and causes extensive tissue damage. Variations in tissue structure significantly influence disease progression, particularly the lower vascular density in peri-implant connective tissue, compromising its ability to combat infection and provide essential nutrients. Blood vessels within this tissue are vital for healing, with angiogenesis playing a key role in immune defense and tissue repair. Enhancing peri-implant soft tissue angiogenesis holds promise for tissue integration and inflammation control. Microgroove surfaces have shown potential in guiding vessel growth, but using subtractive technologies to carve microgrooves on zirconia surfaces may compromise mechanical integrity. In this study, we utilized inkjet printing to prepare bioactive silk fibroin microgrooves (SFMG) coating with different sizes on zirconia surfaces. SFMG coating, particularly with 90 µm width and 10 µm depth, effectively directed human umbilical vein endothelial cells (HUVECs) along microgrooves, promoting their proliferation, migration, and tube formation. The expression of vascular endothelial growth factor A and fibroblast growth factor in HUVECs growing on SFMG coating was upregulated. Additionally, the SFMG coating activated the PI3K-AKT pathway and increased glycolytic enzyme gene expression in HUVECs. In conclusion, SFMG coating enhances HUVEC growth and angiogenesis potential by activating the PI3K-AKT pathway and glycolysis, showing promise for improving tissue integration and mitigating inflammation in zirconia abutments and restorations.

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Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading in situ. Since Mg implants and Mg2+ have been suggested to possess anti-inflammatory properties, the clinically observed soft tissue inflammation around Mg implants is enigmatic. Here, using a rat soft tissue model and a 1–28 d observation period, we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg2+ release. Compared to nondegradable titanium (Ti) implants, Mg degradation exacerbated initial inflammation. Release of Mg degradation products at the tissue-implant interface, culminating at 3 d, actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers, particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d, yet without a cytotoxic effect. Increased vascularization was demonstrated morphologically, preceded by high expression of vascular endothelial growth factor. The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg2+ concentration. Mg implants revealed a thinner fibrous encapsulation compared with Ti. The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.

BACKGROUND Hypoxia modulates inflammation and oxidative stress through hypoxia-inducible factor-1α (HIF-1α). Ferroptosis, an iron-dependent cell death process, is regulated by glutathione peroxidase-4 (GPX4) and involves lipid peroxidation markers like malondialdehyde (MDA). This study evaluates HIF-1α, GPX4, and MDA levels in peri-implant crevicular fluid (PICF) across peri-implant health, mucositis, and peri-implantitis. METHODS PICF samples were collected from 62 implants of 45 participants categorized into peri-implant health (PH), mucositis (PM), and peri-implantitis (PP) groups. Enzyme-linked immunosorbent assay (ELISA) quantified HIF-1α, GPX4, and MDA levels. Statistical analyses, including Kruskal-Wallis and Spearman correlation, assessed biomarker differences and associations. RESULTS Total MDA levels were significantly lower in PM and PP compared to PH (p = 0.014, p = 0.046). GPX4 levels were elevated in PM compared to PH (p = 0.034) but lower in PP than in PM (p < 0.001). While HIF-1α levels did not significantly differ among groups, their concentrations were notably higher in PH. A significant positive correlation was found between the total amounts of HIF-1𝛼 and GPX4 (r = 0.460, p < 0.01). CONCLUSION Our findings demonstrated increased GPX4 and decreased MDA levels in peri-implant mucositis and peri-implantitis compared to peri-implant health, suggesting that ferroptosis may be inhibited in the peri-implant environment. Moreover, the positive correlation between HIF-1α and GPX4 levels indicates a potential regulatory role of hypoxia in modulating ferroptotic pathways in peri-implant tissues. PLAIN LANGUAGE SUMMARY Bone loss around dental implants can lead to serious problems, putting the success of these implants at risk. Understanding how these issues develop is key to preventing and treating them. In the human body, cells can sometimes get damaged and die due to iron and stress caused by harmful molecules. This process, called "ferroptosis," has recently gained attention in oral health research. Our study looked at whether low oxygen levels around dental implants might affect this process. We collected fluid samples from 45 people and measured 3 important substances linked to cell health and stress. We found that in diseased areas, the levels of molecules showing cell damage were lower, while the levels of substances that help protect cells were higher. This suggests that low oxygen conditions might actually help protect tissues around dental implants by preventing cell damage. These insights could help guide better ways to prevent and treat problems related to dental implants in the future.

The presence of foreign materials in the tissues, represented in the present study by the insertion of dental implants, creates artificial structures that can sometimes cause adverse consequences, which implies the obligation to perform a complex medical assessment before inserting dental implants. This assessment appreciates the quality of the tissue, depending on which the use of a certain type of biomaterial is indicated and focuses on a certain surgical technique. We assessed the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of peri-implant soft tissue in patients who did not show mobility or imagistic signs of bone resorption, three months after implant insertion, some of them showing no inflammatory clinical signs. Immunohistochemically, on the sections of the peri-implant mucosa, we assessed the presence of mast cells, vascularization and the process of angiogenesis. Mast cells are key cells actively involved in the pathogenesis of peri-implant inflammation, having an immunomodulatory role. Vasodilation and angiogenesis, determined by the release of chemical mediators by degranulation of mast cells under the action of pathogens, induce tissue remodeling, ensuring the healing and formation of a tissue to form a barrier that effectively prevents the development of a bacterial biofilm. Thus, the control of the activity of these cells is important for the management of the local inflammatory process. The correlations between the clinical, HP and IHC behavior of the peri-implant soft tissue bring important information for the clinic, emphasizing the need to identify a therapeutic strategy to modulate mast cell activity, in order to prevent and treat peri-implant disease, to ensure osseointegration and longer survival of the dental implant.

Abstract Objectives To compare in persons aged 70 years or older the clinical and inflammatory changes occurring around implants and natural teeth during and after a phase of undisturbed plaque accumulation. Material and methods Twenty partially edentulous participants with titanium implants refrained from oral hygiene practices while being clinically monitored in weekly intervals for 21 days. Teeth and implants were then cleaned, oral hygiene resumed, and the participants were further monitored for 3 weeks. Twelve biomarkers were assessed in gingival and peri‐implant crevicular fluid (GCF, PCF). Results During 3 weeks of oral hygiene abstention, the gingival index (GI) continuously increased. On day 21, there were significantly more sites with GI >1 at implants than at teeth. After restarting oral hygiene, the GI decreased markedly in both groups. Throughout the experiment, the plaque index was significantly higher on teeth than on implants. The different biomarkers reacted variably. IL‐1β increased significantly with plaque accumulation. IL‐1β, GM‐CSF, TNF‐α, and IFN‐γ were significantly higher in GCF compared to PCF at day 21. IL‐8 decreased significantly in GCF up to day 14. MIP‐1β decreased significantly in GCF, but not in PCF. At the 3‐week follow‐up, the levels of all biomarkers assessed in GCF and PCF had returned to baseline values. Conclusions In an elderly cohort, plaque accumulation induced an inflammatory reaction around both teeth and implants. Although there was less plaque accumulation on implants, the peri‐implant mucosa showed a stronger clinical response than gingiva.

The aim of this study was to compare the expression of host-derived markers in peri-implant/gingival crevicular fluid (PCF/GCF) and clinical conditions at ceramic implants and contralateral natural teeth. As a secondary objective, we compared zirconia implants with titanium implants. One zirconia implant (ZERAMEX® Implant System) and one contralateral natural tooth were examined in 36 systemically healthy subjects (21 males, 15 females, mean age 58). The levels of Il-1β, Il-1RA, Il-6, Il-8, Il-17, b-FGF, G-CSF, GM-CSF, IFNɣ, MIP-1β, TNF-α, and VEGF were assessed in PCF/GCF using the Bio-Plex 200 Suspension Array System. The plaque index (PI), gingival index (GI), probing depth (PD), and bleeding on probing (BOP) were assessed at six sites around each implant or tooth. Titanium implants were also assessed when present (n = 9). The zirconia implants were examined after a loading period of at least 1.2 years (average 2.2 years). The mean PI was significantly lower at zirconia implants compared to teeth (p = 0.003), while the mean GI, PD, and BOP were significantly higher (p < 0.001). A correlation was found in the expression of Il-1RA, Il-8, G-CSF, MIP-1β, and TNF-α at zirconia implants and teeth. The levels of IL-1β and TNF-α were significantly higher at zirconia implants than at teeth. No significant differences were found between zirconia and titanium implants. A correlation was found between the levels of IL-1RA, IL-8, GM-CSF, and MIP-1β at zirconia and titanium implants. The correlation in the expression of five biomarkers at zirconia implants and teeth, and of four biomarkers at zirconia and titanium implants, is compatible with the existence of a patient-specific inflammatory response pattern. Higher mean GI, PD, and BOP around implants suggests that the peri-implant mucosa may be mechanically more fragile than the gingiva. Similar expression of selected biomarkers at zirconia implants and teeth and at zirconia and titanium implants reflects existence of patient-specific inflammatory response patterns.

Platelet-rich plasma (PRP) has been increasingly used in sports medicine owing to its various advantages. The purpose of our project was to standardize the parameters before performing large-scale clinical trials in the near future to precisely evaluate individual PRP quality. To examine the effects of regular exercise on PRP quality, this study focused on young female athletes, who have been relatively less studied. Blood samples were obtained from female college athletes (n = 35) and ordinary healthy adults (n = 30), which were considered as controls, and leukocyte-rich PRP (L-PRP) was prepared manually. Body composition indices were determined using a bathroom weight scale equipped with an impedance meter. Growth factors and cytokines were quantified using ELISA kits. Platelet-derived growth factor-BB (PDGF-BB) and Transforming-growth factors β1 (TGFβ1) levels (per platelet) in L-PRP were significantly lower in female athletes than in controls. In contrast, Interleukin-1β and Interleukin 1 receptor antagonist (IL-1RA) levels (per platelet and L-PRP) in L-PRP were significantly higher in athletes, and this difference was more prominent in IL-1RA. These findings suggest that L-PRP from athletes may facilitate the inflammatory phase of the healing process by regulating the pro-inflammatory and anti-inflammatory balance. These chemical compositions can be adopted as “must-check” parameters to characterize individual PRP preparations prior to clinical trials.