Experimental Model of Ligature-Induced Peri-Implantitis in Mice.

Dental implants have a high success and survival rate. However, complications such as peri-implantitis (PI) are highly challenging to treat. PI is characterized by inflammation in the tissues around dental implants with progressive loss of supporting bone. To optimize dental implants' longevity in terms of health and functionality, it is crucial to understand the peri-implantitis pathophysiology. In this regard, using mouse models in research has proven clear benefits in recreating clinical circumstances. This study aimed to describe an experimental model of ligature-induced peri-implantitis in mice and determine whether there is effectiveness in inducing this disease, given the observed bone and tissue changes. The experimental peri-implantitis induction comprehends the following steps: teeth extraction, implant placement, and ligature-inducted PI. A sample of eighteen 3-week-old C57BL/6J male mice was divided into two groups, ligature (N=9) and control non-ligature (N=9). The evaluation of clinical, radiographical, and histological factors was performed. The ligature group showed significantly higher bone loss, increased soft tissue edema, and apical epithelial migration than the non-ligature group. It was concluded that this pre-clinical model can successfully induce peri-implantitis in mice.

Ultrastructural and immunohistochemical evaluation of hyperplastic soft tissues surrounding dental implants in fibular jaws.

In reconstructive surgery, complications post-fibula free flap (FFF) reconstruction, notably peri-implant hyperplasia, are significant yet understudied. This study analyzed peri-implant hyperplastic tissue surrounding FFF, alongside peri-implantitis and foreign body granulation (FBG) tissues from patients treated at the Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital. Using light microscopy, pseudoepitheliomatous hyperplasia, anucleate and pyknotic prickle cells, and excessive collagen deposition were observed in FFF hyperplastic tissue. Ultrastructural analyses revealed abnormal structures, including hemidesmosome dilation, bacterial invasion, and endoplasmic reticulum (ER) swelling. In immunohistochemical analysis, unfolded protein-response markers ATF6, PERK, XBP1, inflammatory marker NFκB, necroptosis marker MLKL, apoptosis marker GADD153, autophagy marker LC3, epithelial-mesenchymal transition, and angiogenesis markers were expressed variably in hyperplastic tissue surrounding FFF implants, peri-implantitis, and FBG tissues. NFκB expression was higher in peri-implantitis and FBG tissues compared to hyperplastic tissue surrounding FFF implants. PERK expression exceeded XBP1 significantly in FFF hyperplastic tissue, while expression levels of PERK, XBP1, and ATF6 were not significantly different in peri-implantitis and FBG tissues. These findings provide valuable insights into the interconnected roles of ER stress, necroptosis, apoptosis, and angiogenesis in the pathogenesis of oral pathologies, offering a foundation for innovative strategies in dental implant rehabilitation management and prevention.

Sustained Release of Salicylic Acid for Halting Peri-Implantitis Progression in Healthy and Hyperglycemic Systemic Conditions: A Gottingen Minipig Model.

To develop a peri-implantitis model in a Gottingen minipig and evaluate the effect of local application of salicylic acid poly(anhydride-ester) (SAPAE) on peri-implantitis progression in healthy, metabolic syndrome (MS), and type-2 diabetes mellitus (T2DM) subjects. Eighteen animals were allocated to three groups: (i) control, (ii) MS (diet for obesity induction), and (iii) T2DM (diet plus streptozotocin for T2DM induction). Maxillary and mandible premolars and first molar were extracted. After 3 months of healing, four implants per side were placed in both jaws of each animal. After 2 months, peri-implantitis was induced by plaque formation using silk ligatures. SAPAE polymer was mixed with mineral oil (3.75 mg/µL) and topically applied biweekly for up to 60 days to halt peri-implantitis progression. Periodontal probing was used to assess pocket depth over time, followed by histomorphologic analysis of harvested samples. The adopted protocol resulted in the onset of peri-implantitis, with healthy minipigs taking twice as long to reach the same level of probing depth relative to MS and T2DM subjects (∼3.0 mm), irrespective of jaw. In a qualitative analysis, SAPAE therapy revealed decreased levels of inflammation in the normoglycemic, MS, and T2DM groups. SAPAE application around implants significantly reduced the progression of peri-implantitis after ∼15 days of therapy, with ∼30% lower probing depth for all systemic conditions and similar rates of probing depth increase per week between the control and SAPAE groups. MS and T2DM conditions presented a faster progression of the peri-implant pocket depth. SAPAE treatment reduced peri-implantitis progression in healthy, MS, and T2DM groups.

Comparative Assessment of Catalase Levels in Peri-Implant Health and Disease.

Peri-implant disease pathogenesis is similar to periodontal disease pathogenesis resulting in production of pro-inflammatory mediators. These mediators alter the redox balance leading to decrease in antioxidants, among which catalase is one of the enzymatic antioxidants. The aim of the study was to compare the levels of catalase in peri-implant health and disease. The present observational study was carried out from June 2022 to December 2022 in the Department of Implantology, Saveetha Dental College and Hospitals, Chennai, India. A total of 60 patients with peri-implant health (Group 1; n = 20), peri-implant mucositis (Group 2; n = 20) and peri-implantitis (Group 3; n = 20) were enrolled. Unstimulated salivary samples were collected and subjected to ELISA for catalase analysis. Catalase levels were then compared between the groups using ANOVA. The mean catalase level in peri-implant health, peri-implant mucositis, peri-implanti-tis were 25.07 ± 0.44 U/mL, 18.5 6 ± 0.65 U/mL, and 11.25 ± 0.76 U/mL respectively. The difference between the three groups were statistically significant (P < 0.05). Catalase level decreases with severity of peri-implant diseases. Therefore, catalase can be used as a diagnostic marker for peri-implant diseases.

Correlation of C-Reactive Protein and Severity of Peri-Implant Diseases.

Peri-implant disease pathogenesis is similar to periodontal disease pathogenesis resulting in production of pro-inflammatory mediators. These mediators are released during the inflammation phase, among which C-reactive protein (CRP) is one of the acute phase reactants. The aim of the study was to correlate the levels of CRP with the severity of peri-implant diseases. The present observational study was carried out from June 2022 to December 2022 in the Department of Implantology, Saveetha Dental College and Hospitals, Chennai, India. A total of 60 patients with peri-implant health (n = 20), peri-mucositis (n = 20) and peri-implantitis (n = 20) were enrolled. Unstimulated salivary samples were collected and subjected to latex agglutination assay for CRP analysis. CRP levels were then correlated with severity of peri-implant diseases. The mean CRP level in peri-implant health, peri-implant mucositis, peri-implantitis were 0.25 ± 0.36 mg/dl, 3.56 ± 0.85 mg/dl and 5.07 ± 0.74 mg/dl, respectively. Pearson correlation coefficient analysis revealed a strong positive correlation between CRP and peri-implant parameters suggesting that the CRP level increased as the severity of peri-implant disease increased. CRP level increases with severity of peri-implant diseases and there exists a positive correlation between CRP level and peri-implant parameters. Therefore, CRP can be used as a diagnostic marker for peri-implant diseases.

Proximal Periodontal Support Adjacent to Untreated Peri-implantitis Lesions: A Cross-Sectional Analysis.

PURPOSE: To assess site-related features of peri-implantitis occurring adjacent to teeth and its association with the proximal periodontal bone level. MATERIALS AND METHODS: Periapical radiographs were collected from partially edentulous patients exhibiting peri-implantitis adjacent to teeth. The following variables were quantified: intrabony defect width (DW), implant marginal bone loss (MBLi), tooth marginal bone loss (MBLt), implant-tooth distance (ITd), intrabony defect angulation (DA), adjacent periodontal bone peak height (ABPh), and implant-tooth angulation (ITa). A correlation matrix using the Spearman correlation coefficient was created to explore the dependence of these variables. Univariate linear regression analysis was carried out by means of generalized estimating equations (GEE), using MBLt as dependent variable. RESULTS: Overall, 61 patients and 84 implants were included in this study, consisting of a total of 105 implant sites facing adjacent teeth. This resulted in 515 linear and 194 angular measurements. A total of 11 different statistically significant associations were demonstrated between the different variables analyzed. Moreover, the univariate regression analysis revealed significant positive associations between MBLt and MBLi (P = .013) and between MBLt and periodontitis (PD) (P = .014). These associations were confirmed in the multivariate model. CONCLUSIONS: Teeth adjacent to untreated peri-implantitis lesions are associated with proximal loss of periodontal support. This finding is more remarkable in scenarios that display short implant-tooth distance.

Titanium particles in peri-implantitis: distribution, pathogenesis and prospects.

Peri-implantitis is one of the most important biological complications in the field of oral implantology. Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease's prevention and treatment. The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated. Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue. Notably, the concentration of titanium particles increases significantly at peri-implantitis sites, suggesting titanium particles as a potential risk factor for the condition. Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement. However, it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues. This review summarizes the distribution of titanium particles around the implant, the potential roles in peri-implantitis and the prevalent prevention strategies, which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.

Evaluation of IL-4, MIP-1α, and MMP-9 gene expression levels in peri-implant tissues in peri-implantitis.

This case-control study evaluated the gene expression levels of interleukin (IL)-4, macrophage inflammatory protein type 1 alpha (MIP-1α), and metalloproteinase (MMP)-9, factors involved in the formation of giant cells in healthy peri-implant tissue and peri-implantitis. Thirty-five subjects (15 healthy and 20 with peri-implantitis), who met the inclusion and exclusion criteria, were included in this study. The peri-implant tissue biopsies were subjected to total RNA extraction, DNAse treatment, and cDNA synthesis. Subsequently, the reaction of real-time PCR was performed to evaluate the gene expression levels of IL-4, MIP-1α, and MMP-9 concerning the reference gene. IL-4 gene expression showed higher (18-fold) values in the Peri-Implantitis Group of Patients when compared with the Healthy (Control) Group (p<0.0001). Although MIP- 1α and MMP-9 gene expression levels were higher in diseased implants, they showed no significant differences (p=0.06 and p=0.2337), respectively. Within the limitations of this study, the results showed that in tissues affected by peri-implantitis, only levels of Il-4 were increased when compared with tissues in the control group.

Application of Immediate Implant Placement Techniques in Peri-implantitis Modeling.

OBJECTIVES: To explore the use of immediate implant placement technique in peri-implantitis modeling, shorten the modeling period, and obtain similar effects. MATERIALS AND METHODS: Eighty rats were divided into 4 groups: immediate placement (IP), delayed placement (DP), IP-ligation (IP-L) and DP-ligation (DP-L). In the DP and DP-L groups, implants were placed 4 weeks after tooth extraction. In the IP and IP-L groups, implants were placed immediately. Four weeks later, the implants were ligated to induce peri-implantitis in the DP-L and IP-L groups. RESULTS: Nine implants were lost (3 in the IP-L and 2 each in the IP, DP, and DP-L group). The bone level decreased after ligation, and the buccal and lingual bone levels were lower in IP-L versus DP-L. The implant pullout strength was decreased after ligation. Micro-CT showed bone parameters were decreased after ligation, and the percent bone volume was higher in IP versus DP. Histology showed that the percent of CD4 + cells and IL-17 + cells was increased after ligation and higher in IP-L versus DP-L. CONCLUSIONS: We successfully introduced immediate implant placement into the modeling of peri-implantitis and observed similar bone resorption and more soft tissue inflammation in a shorter time.

AdipoAI suppresses osteoclastogenesis by activating AdipoR1/APPL1: An in vivo experimental study in diabetes-associated peri-implantitis.

AIM: Diabetics experience severe peri-implant inflammatory bone damage. We aimed to provide powerful evidence supporting the novel adiponectin receptor agonist AdipoAI in treating diabetes-associated peri-implantitis. MATERIALS AND METHODS: Twenty-four ZDF-Leprfa/Crl rats were randomly allocated to three groups (N = 8). After feeding with a high-fat diet to establish diabetic rats, experimental peri-implantitis was induced by implanting titanium rods (1.5 mm diameter and 20 mm length) contaminated with Staphylococcus aureus into the femurs. Radiographic evaluation, microCT, histological analyses and qRT-PCR were used to detect inflammatory infiltration and bone destruction. In vitro, the inhibition by AdipoAI of osteoclastogenesis, including the number and function of osteoclasts, was investigated by TRAP staining, immunofluorescence, qRT-PCR and Western blotting. Immunofluorescence, qRT-PCR and Western blotting were also utilized to explore AdipoR1, APPL1, NF-κB and Wnt5a-Ror2 signalling molecules in this process. One-way ANOVA with Tukey's post hoc test was used to compare the data. RESULTS: AdipoAI reduced inflammation and bone destruction caused by peri-implantitis in diabetic rats, which were manifested by a reduction in F4/80-positive macrophage infiltration by 72%, the number of osteoclasts by 58% and the levels of cytokines (p < .05) in disease group. In vitro, 1 µM AdipoAI decreased the number of osteoclasts to 51%, inhibited F-actin ring formation and reduced the levels of related markers (p < .05). Mechanistically, AdipoAI activated AdipoR1/APPL1 and conversely suppressed the phosphorylation of IκB-α, nuclear translocation of P65 and the Wnt5a-Ror2 signalling pathway (p < .05). CONCLUSIONS: AdipoAI suppressed osteoclastogenesis in diabetes-associated peri-implantitis by inhibiting the NF-κB and Wnt5a-Ror2 pathways via the AdipoR1/APPL1 axis.

[Comparison of three methods for establishing rat peri-implantitis model].

OBJECTIVE: To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods. METHODS: Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1ß (IL-1ß). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death. RESULTS: After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1ß in the test groups were higher than those in the control group (P < 0.05). CONCLUSION: Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

Detecting lymphadenopathy affected by peri-implantitis using diffusion-weighted magnetic resonance imaging.

PURPOSE: This study aimed to assess peri-implantitis-induced lymphadenopathy on diffusion-weighted imaging (DWI). METHODS: This retrospective study was conducted from October 2017 to March 2020 in patients with and without peri-implantitis who underwent magnetic resonance imaging (MRI). Patients in the peri-implantitis group had radiographically confirmed loss of alveolar bone > 2.0 mm and clinical findings such as bleeding on probing, suppuration of tissues surrounding the teeth, probing-pocket depth of > 4 mm, pain on implant function, and clinical implant mobility, whereas those without peri-implantitis had none of the abovementioned clinical findings. The Mann-Whitney U test was used to compare groups, using lymph node (LN) short-axis diameters and apparent diffusion coefficients (ADCs) as the criterion variables and presence or absence of peri-implantitis as the explanatory variable. Receiver operating characteristic (ROC) analysis was done to investigate the effectiveness of LN size and ADC use in detecting peri-implantitis-induced lymphadenopathy. Statistical significance was established at P < 0.05. RESULTS: There were 66 lymph nodes from 12 patients analyzed. The mean LN size and ADC were significantly higher in patients with peri-implantitis than in those without (P < 0.01). ROC curve analysis showed cut-off LN sizes of 4.78 and 4.84 mm and cut-off ADCs of 1.12 and 1.09 for lymphadenopathy affected by peri-implantitis corresponding to levels IB and II, respectively. CONCLUSIONS: Cervical lymphadenopathy may be an inflammatory finding associated with peri-implantitis.

Titanium particles in peri-implantitis: distribution, pathogenesis and prospects / 国际口腔科学杂志·英文版

Peri-implantitis is one of the most important biological complications in the field of oral implantology. Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease's prevention and treatment. The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated. Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue. Notably, the concentration of titanium particles increases significantly at peri-implantitis sites, suggesting titanium particles as a potential risk factor for the condition. Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement. However, it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues. This review summarizes the distribution of titanium particles around the implant, the potential roles in peri-implantitis and the prevalent prevention strategies, which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.

Comparison of three methods for establishing rat peri-implantitis model / 北京大学学报(医学版)

OBJECTIVE@#To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods.@*METHODS@#Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1β (IL-1β). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death.@*RESULTS@#After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1β in the test groups were higher than those in the control group (P < 0.05).@*CONCLUSION@#Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

Bone defect development in experimental canine peri-implantitis models: a systematic review.

PURPOSE: To provide a systematic overview of preclinical research regarding bone defect formation around different implant surfaces after ligature-induced peri-implantitis models in dogs. Two focused questions were formulated: 'How much bone loss can be expected after a certain time of ligature induced peri-implantitis?' and 'Do different implant types, dog breeds and study protocols differ in their extent of bone loss?' MATERIALS AND METHODS: A systematic literature search was conducted on four databases (MEDLINE, Web of Science, EMBASE and Scopus). Observations, which consisted of bone defects measured directly after ligature removal in canine models, were included and analysed. Two approaches were used to analyse the relatively heterogeneous studies that fulfilled the inclusion criteria. First, separate simple linear regressions were calculated for each study and implant surface, for which observations were available across multiple time points. Second, a linear mixed model was specified for the observations at 12 weeks after ligature initiation, and assessing the potential influencing factors on defect depth was explored using lasso regularisation. RESULTS: Thirty-six studies with a total of 1082 implants were included after. Bone loss was determined at different time points, either with clinical measurements radiographically or histologically. Different implant groups [e.g. turned, sand-blasted-acid-etched (SLA), titanium-plasma-sprayed (TPS) and other rough surfaces] were assessed and described in the studies. A mean incremental defect depth increase of 0.08 mm (SD: -0.01-0.28 mm) per week was observed. After 12 weeks, the defect depths ranged between 0.7 and 5 mm. Based on the current data set, implant surface could not be statistically identified as an essential factor in defect depth after 12 weeks of ligature-induced peri-implantitis. CONCLUSION: Expectable defect depth after a specific time of ligature-induced peri-implantitis can vary robustly. It is currently impossible to delineate apparent differences in bone loss around different implant surfaces.

The role of foreign body response in peri-implantitis: What is the evidence?

Historically, there has been broad consensus that osseointegration represents a homeostasis between a titanium dental implant and the surrounding bone, and that the crestal bone loss characteristic of peri-implantitis is a plaque-induced inflammatory process. However, this notion has been challenged over the past decade by proponents of a theory that considers osseointegration an inflammatory process characterized by a foreign body reaction and peri-implant bone loss as an exacerbation of this inflammatory response. A key difference in these two schools of thought is the perception of the relative importance of dental plaque in the pathogenesis of crestal bone loss around implants, with obvious implications for treatment. This review investigates the evidence for a persistent foreign body reaction at osseointegrated dental implants and its possible role in crestal bone loss characteristic of peri-implantitis. Further, the role of implant-related material release within the surrounding tissue, particularly titanium particles and corrosion by-products, in the establishment and progression in peri-implantitis is explored. While it is acknowledged that these issues require further investigation, the available evidence suggests that osseointegration is a state of homeostasis between the titanium implant and surrounding tissues, with little evidence that a persistent foreign body reaction is responsible for peri-implant bone loss after osseointegration is established. Further, there is a lack of evidence for a unidirectional causative role of corrosion by-products and titanium particles as possible non-plaque related factors in the etiology of peri-implantitis.

Does implant location influence the risk of peri-implantitis?

Peri-implantitis is characterized by nonreversible and progressive loss of supporting bone and is associated with bleeding and/or suppuration on probing. Peri-implant disease is considered as the main etiologic factor related to implant failure. Peri-implant disease has a pathogenesis similar to that of periodontal disease, both being triggered by an inflammatory response to the biofilm accumulation. Although the prevalence of peri-implantitis has been evaluated by several clinical studies with different follow-ups, there are currently little data on the impact of implant location and the prevalence of peri-implantitis. The aim of this review, therefore, was to summarize the evidence concerning the prevalence of peri-implantitis in relation to implant location and associated risk predictors. Even though most studies evaluating the prevalence of peri-implantitis in relation to implant location are cross-sectional or retrospective, they suggest that the occurrence of peri-implantitis is most prevalent in the anterior regions of the maxilla and mandible. Moreover, it seems that there is a higher prevalence of peri-implantitis in the maxilla than in the mandible.

Quantitative Evaluation of Inflammatory Markers in Peri-Implantitis and Periodontitis Tissues: Digital vs. Manual Analysis-A Proof of Concept Study.

Background and Objectives: In dentistry, the assessment of the histomorphometric features of periodontal (PD) and peri-implant (PI) lesions is important to evaluate their underlying pathogenic mechanism. The present study aimed to compare manual and digital methods of analysis in the evaluation of the inflammatory biomarkers in PI and PD lesions. Materials and Methods: PD and PI inflamed soft tissues were excised and processed for histological and immunohistochemical analyses for CD3+, CD4+, CD8+, CD15+, CD20+, CD68+, and CD138+. The obtained slides were acquired using a digital scanner. For each marker, 4 pictures per sample were extracted and the area fraction of the stained tissue was computed both manually using a 594-point counting grid (MC) and digitally using a dedicated image analysis software (DC). To assess the concordance between MC and DC, two blinded observers analysed a total of 200 pictures either with good quality of staining or with non-specific background noise. The inter and intraobserver concordance was evaluated using the intraclass coefficient and the agreement between MC and DC was assessed using the Bland-Altman plot. The time spent analysing each picture using the two methodologies by both observers was recorded. Further, the amount of each marker was compared between PI and PD with both methodologies. Results: The inter- and intraobserver concordance was excellent, except for images with background noise analysed using DC. MC and DC showed a satisfying concordance. DC was performed in half the time compared to MC. The morphological analysis showed a larger inflammatory infiltrate in PI than PD lesions. The comparison between PI and PD showed differences for CD68+ and CD138+ expression. Conclusions: DC could be used as a reliable and time-saving procedure for the immunohistochemical analysis of PD and PI soft tissues. When non-specific background noise is present, the experience of the pathologist may be still required.

Hybrid system with stable structure of hard/soft tissue substitutes induces re-osseointegration in a rat model of biofilm-mediated peri-implantitis.

Re-osseointegration of an infected/contaminated dental implant poses major clinical challenges. We tested the hypothesis that the application of an antibiotic-releasing construct, combined with hard/soft tissue replacement, increases the efficacy of reconstructive therapy. We initially fabricated semi-flexible hybrid constructs of ß-TCP/PHBHHx, with tetracycline (TC) (TC amounts: 5%, 10%, and 15%). Thereafter, using in vitro assays, TC release profile, attachment to rat bone marrow-derived stem cells (rBMSCs) and their viability as well as anti-bacterial activity were determined. Thereafter, regenerative efficacies of the three hybrid constructs were assessed in a rat model of peri-implantitis induced by Aggregatibacter actinomycetemcomitans biofilm; control animals received ß-TCP/Bio-Gide and TC injection. Eight weeks later, maxillae were obtained for radiological, histological, and histomorphometric analyses of peri-implant tissues. Sulcus bleeding index was chronologically recorded. Serum cytokines levels of IL-6 and IL-1ß were also evaluated by enzyme-linked immunosorbent assay. Substantial amounts of tetracycline, from hybrid constructs, were released for 2 weeks. The medium containing the released tetracycline did not affect the adhesion or viability of rBMSCs; however, it inhibited the proliferation of A. actinomycetemcomitans. Osteogenesis and osseointegration were more marked for the 15% hybrid construct group than the other two groups. The height of attachment and infiltration of inflammatory cells within fibrous tissue was significantly reduced in the experimental groups than the control group. Our protocol resulted in re-osseointegration on a biofilm-contaminated implant. Thus, an antibiotic releasing inorganic/organic construct may offer a therapeutic option to suppress infection and promote guided tissue regeneration thereby serving as an integrated multi-layer substitute for both hard/soft tissues.

Study on the immunopathological effect of titanium particles in peri-implantitis granulation tissue: A case-control study.

OBJECTIVES: To identify titanium particles (TPs) in biopsy specimens harvested from peri-implantitis lesions and secondarily to study the histopathological characteristics in peri-implantitis compared to periodontitis, in order to evaluate whether the presence of TPs could alter respective inflammatory patterns. MATERIAL AND METHODS: Biopsies containing granulation tissue were harvested during routine surgical treatment in 39 peri-implantitis cases and 35 periodontitis controls. Serial sections were obtained using titanium-free microtome blades. The first and last sections of the peri-implantitis specimens were used for identification of TPs by scanning electron microscopy coupled with dispersive X-ray spectrometry. Intermediate sections and periodontitis specimens were processed for descriptive histological study using haematoxylin-eosin staining and for immunohistochemical analysis using CD68, IL-6, Nf-kB and VEGF markers. RESULTS: TPs were identified in all peri-implantitis specimens as free metal bodies interspersed within granulation tissue. However, presence of macrophages or multinucleated giant cells engulfing the TPs were not identified in any specimen. Peri-implantitis granulations were characterized by a chronic inflammatory infiltrate rich in neutrophils. About half of peri-implantitis patients exhibited a subacute infiltrate characterized with lymphocytes interweaved with neutrophils and eosinophils. When compared to periodontitis, peri-implantitis tissues showed higher proportions of macrophages and a more intense neovascularization, based on significantly higher expression of CD68 and VEGF respectively. CONCLUSION: TPs were identified in all peri-implantitis specimens, but without evidencing any foreign body reaction suggestive for direct pathological effects of TPs. The peri-implantitis granulation tissue was characterized by intense neovascularization and presence of a chronic inflammatory infiltrate dominated by plasma cells, neutrophils and macrophages.