Immune cell composition and inflammatory profile of human peri-implantitis and periodontitis lesions.

Peri-implantitis (PI) and periodontitis (PD) are common oral inflammatory diseases, which seem to exhibit critical differences in some of their molecular features. Thus, we assessed the immune cell composition of PI and PD lesions and the corresponding inflammatory profile in soft tissues and crevicular fluid. PI, PD, and control patients were recruited (n = 62), and soft tissue biopsies were collected during surgery. Crevicular fluid around implant or tooth was collected. The proportions of major immune cell populations in tissues were analyzed by flow cytometry, and the inflammatory profile in tissue and crevicular fluid by a multiplex immunoassay. No significant difference was seen between PI and PD lesions in the proportions of immune cells. PI tissues showed an increased frequency of B cells in comparison with control tissues, along with higher levels of IL-1ß, TNF-α, IL-4, and BAFF in tissue and crevicular fluid. Moreover, TNF-α, IL-17A, and BAFF were higher in PI tissues, but not in PD, than in control tissues. The immune cell composition did not differ significantly between PI and PD, but an enhanced inflammatory profile was seen in PI tissue. PI lesions were enriched in B cells, and displayed increased levels of IL-1ß, TNF-α, IL-4, and BAFF in both tissue and crevicular fluid.

Diagnostic methods/parameters to monitor peri-implant conditions.

The diagnostic accuracy of clinical parameters, including visual inspection and probing to monitor peri-implant conditions, has been regarded with skepticism. Scientific evidence pointed out that primary diagnostic tools (chairside) seem to be highly specific, while their sensitivity is lower compared with their use in monitoring periodontal stability. Nonetheless, given the association between pocket depth at teeth and implant sites and the aerobic/anaerobic nature of the microbiome, it seems plausible for pocket probing depth to be indicative of disease progression or tissue stability. In addition, understanding the inflammatory nature of peri-implant diseases, it seems reasonable to advocate that bleeding, erythema, ulceration, and suppuration might be reliable indicators of pathology. Nevertheless, single spots of bleeding on probing may not reflect peri-implant disease, since implants are prone to exhibit bleeding related to probing force. On the other side, bleeding in smokers lacks sensitivity owing to the decreased angiogenic activity. Hence, the use of dichotomous scales on bleeding in the general population, in contrast to indices that feature profuseness and time after probing, might lead to false positive diagnoses. The definitive distinction between peri-implant mucositis and peri-implantitis, though, relies upon the radiographic evidence of progressive bone loss that can be assessed by means of two- and three-dimensional methods. Accordingly, the objective of this review is to evaluate the existing clinical and radiographic parameters/methods to monitor peri-implant conditions.

Radiographic assessment of the peri-implant site.

While peri-implant mucositis relies solely on clinical parameters, radiological assessment becomes indispensable for diagnosing peri-implantitis. Intraoral radiography, with its simplicity of application, low radiation exposure, and adequate representation of peri-implant structures, stands out as the standard of care for both immediate and follow-up assessments. Standardization by custom-made radiologic splints allows for excellent comparability with previous images and allows for the determination of even small changes in contour and density of the peri-implant bone. Furthermore, other radiographic modalities like panoramic radiography and cone beam computed tomography (CBCT) may provide useful features for specific patients and clinical cases while also showing innate limitations. Beyond the assessment of the marginal peri-implant bone level as the crucial parameter of clinical relevance, radiologic assessment may reveal various other findings related to the prosthetic restoration itself, the precision of its fit to the implant, and the peri-implant soft and hard tissues. Since such findings can be crucial for the assessment of peri-implant health and the implants' prognosis, a systematic diagnostic evaluation pathway for a thorough assessment is recommended to extract all relevant information from radiologic imaging. This article also provides an overview of the clinical and chronological indications for different imaging modalities in peri-implant issues.

Introduction to the Diagnostics in Periodontology and Implant Dentistry issue.

Chronic inflammatory periodontal disease and its related condition, peri-implant disease, are highly prevalent globally and require accurate and speedy diagnosis. The focus of this volume dedicated to diagnostics is to cover modern enhancements in accuracy, simplicity and speed. An international assortment of experts has been tasked with reviewing defined areas of current best practice as well innovation in the field of periodontitis and peri-implantitis diagnostics. Periodontitis and peri-implantitis are irreversible, chronic, cumulative conditions propagated by bacteria and host factors, which involve soft and hard tissue changes, and these changes are measured in the diagnostic process. Clinically relevant modifications to the healthy state are detected using clinical, radiological and laboratory or point of care testing, and these testing approaches are critically reviewed at length in this state-of-the-art resume of periodontal diagnostics.

Etiology, pathogenesis and treatment of peri-implantitis: A European perspective.

Peri-implantitis is a plaque-associated pathological condition occurring in tissues around dental implants. It is characterized by inflammation in the peri-implant mucosa and progressive loss of supporting bone. Over the last 30 years, peri-implantitis has become a major disease burden in dentistry. An understanding of the diagnosis, etiology and pathogenesis, epidemiology, and treatment of peri-implantitis must be a central component in undergraduate and postgraduate training programs in dentistry. In view of the strong role of European research in periodontology and implant dentistry, the focus of this review was to address peri-implantitis from a European perspective. One component of the work was to summarize new and reliable data on patients with dental implants to underpin the relevance of peri-implantitis from a population perspective. The nature of the peri-implantitis lesion was evaluated through results presented in preclinical models and evaluations of human biopsy material together with an appraisal of the microbiological characteristics. An overview of strategies and outcomes presented in clinical studies on nonsurgical and surgical treatment of peri-implantitis is discussed with a particular focus on end points of therapy and recommendations presented in the S3 level Clinical Practice Guideline for the prevention and treatment of peri-implant diseases.

The use of patient-related outcomes (PRO) and experience (PRE) in assessing the periodontal and implant patient.

The purpose of this review was to summarize the evidence with regard to behavioral and psychosocial assessment of the periodontitis patient, the candidate for implant therapy, and the peri-implantitis patient. Periodontitis has an adverse effect on quality of life and its treatment can lead to significant improvements experienced by the patient. The latter is true for rehabilitation with dental implants, although patients harbor diverse expectations and perceptions of implant therapy, which can often interfere with satisfaction and/or influence long-term success. A thorough behavioral assessment of the candidate for implant therapy is essential, which should include, perceptions, expectations, as well as risk for behavioral disorders. Remedial action is essential to correct misperceptions and any identified risks. Finally, patients have limited awareness of limited ability to identify signs of peri-implantitis. The diagnosis of peri-implantitis can be a cause of significant distress, resentment, and loss of trust to the treatment and the caregivers. Despite documented value in clinical research, currently available instruments assessing patient-reported outcomes have little application in day-to-day clinical practice. Face-to-face patient to doctor open-ended communication remains the most effective way to comprehensively establish the long-term "therapeutic alliance" essential for the long journey for the periodontitis patient.

Tooth- and implant-related prognostic factors in treatment planning.

Following a comprehensive patient examination, including the assessment of periodontal and peri-implant diseases as well as considering the patient's needs, a pretherapeutic prognosis for each tooth and implant is given. Teeth and implants with a secure pretherapeutic prognosis require simple procedures and may be regarded as secure abutments for function and with a doubtful pretherapeutic prognosis usually need a comprehensive therapy. Such teeth and implants must be brought into the category with a secure prognosis by means of additional therapy such as endodontic, restorative, and surgical procedures. Teeth and implants with a hopeless pretherapeutic prognosis should be extracted/explanted during the initial phase of cause-related therapy (i.e., infection control). For example, teeth with vertical root fracture or unrestorable caries and implants with mobility or unrestorable malposition fall into the category of hopeless units. The primary goal of periodontal and peri-implant therapy should be to arrest disease progression. The latest consensus statement highlights that periodontitis can be successfully controlled and treated teeth can be retained for life. Nevertheless, for patients with uncontrolled contributing factors, the endpoints might not always be achievable, and low disease activity may be an acceptable therapeutic goal. Similarly, the management of peri-implantitis frequently requires surgical intervention following nonsurgical therapy due to incomplete treatment outcomes. Different surgical modalities can be effective and lead to significant improvement; however, achieving complete resolution of peri-implantitis is challenging, not always predictable, and can depend on multiple baseline factors. Therefore, this review aims at summarising available evidence on the rationale for incorporating systemic, lifestyle-related, clinical, and radiographic prognostic factors into treatment planning of patients diagnosed with periodontal and peri-implant diseases.

Diagnostic measures for monitoring and follow-up in periodontology and implant dentistry.

This review discusses the role of diagnostic measures in the lifelong management of periodontal disease and peri-implant complications. After active treatment, these conditions require regular monitoring of the supporting structures of teeth and dental implants to assess bone and soft tissue health over time. Several clinical measures have been developed for the routine assessment of periodontal and peri-implant tissues, including periodontal and peri-implant probing, bleeding on probing, intraoral radiography, biomarker analysis, and microbiological testing. This review highlights the evolution of diagnostic practices, integrating traditional methods with emerging technologies such as resonance frequency analysis and ultrasound imaging to provide a holistic view of peri-implant health assessment. In addition to objective measurements, patient risk factors are considered. The goals of periodontal and peri-implant maintenance are to control disease activity and stabilize tissues through supportive care, which includes diagnostic measures at follow-up visits. This enables clinicians to monitor treatment outcomes, assess health status, and detect recurrence or progression early through routine evaluation, allowing additional interventions, including adjustment of supportive therapy intervals, to further improve and maintain periodontal and peri-implant stability over time.

CXCL5/CXCL8 induces neutrophilic inflammation in peri-implantitis.

OBJECTIVE AND BACKGROUND: This research aimed to examine the role of C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 8 (CXCL8; also known as IL-8) in neutrophilic inflammation triggered by peri-implantitis and to shed light on the underlying mechanisms that link them to the development of this condition. MATERIALS: This study included 40 patients who visited the Department of Periodontology at Kyungpook University Dental Hospital. They were divided into two groups based on their condition: healthy implant (HI) group (n = 20) and peri-implantitis (PI) group (n = 20). Biopsy samples of PI tissue were collected from the patients under local anesthesia. HI tissue was obtained using the same method during the second implant surgery. To construct libraries for control and test RNAs, the QuantSeq 3' mRNA-Seq Library Prep Kit (Lexogen, Inc., Austria) was used according to the manufacturer's instructions. Samples were pooled based on representative cytokines obtained from RNA sequencing results and subjected to Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Hematoxylin and eosin staining, and immunohistochemistry (IHC) analysis were performed to visually assess expression levels and analyze tissue histology. Student's t-test was employed to conduct statistical analyses. RESULTS: Initially, heatmaps were used to examine gene expression variations between the HI and PI groups based on the results of RNA sequencing. Notably, among various cytokines, CXCL5 and CXCL8 had the highest expression levels in the PI group compared with the HI group, and they are known to be associated with inflammatory responses. In the gingival tissues, the expression of genes encoding cytokines such as interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-6, and CXCL5/CXCL8 was assessed via RT-qPCR. The mRNA expression level of CXCL5/CXCL8 significantly increased in the PI group compared with the HI group (p < .045). Contrarily, the mRNA expression level of interleukin 36 receptor antagonist (IL36RN) significantly decreased (p < .008). IHC enabled examination of the distribution and intensity of CXCL5/CXCL8 protein expression within the tissue samples. Specifically, increased levels of CXCL5/CXCL8 promote inflammatory responses, cellular proliferation, migration, and invasion within the peri-implant tissues. These effects are mediated through the activation of the PI3K/Akt/NF-κB signaling pathway. CONCLUSIONS: This study found that the PI sites had higher gene expression level of CXCL8/CXCL5 in the soft tissue than HI sites, which could help achieve more accurate diagnosis and treatment planning.

Levels of matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-3, osteopontin, pentraxin-3, and thymic stromal lymphopoietin in crevicular fluid samples from peri-implantitis, periodontitis, and healthy sites.

AIM: Periodontitis and peri-implantitis are chronic inflammatory diseases characterized by the destruction of supporting tissues. Despite some similarities, it is essential to understand the differences in how these diseases elicit unique host responses within the oral tissues, including the production of selected matrix metalloproteinases (MMPs) and inflammatory mediators involved in tissue remodelling. The aim of this study was to evaluate the levels of proteolytic enzymes MMP-1, MMP-2, MMP-3, as well as the inflammatory mediators osteopontin (OPN), pentraxin-3 (PTX3), and thymic stromal lymphopoietin (TSLP) in crevicular fluid samples collected from healthy, periodontitis-affected, and peri-implantitis sites. METHODS: Gingival crevicular fluid (GCF) and peri-implant crevicular fluid (PICF) samples were collected from healthy and diseased teeth and implant sites of 163 patients. The MMP-1, MMP-2, MMP-3, OPN, PTX3, and TSLP levels were determined using commercially available immunoassays. A linear mixed model procedure was adopted for multilevel analyses, using biomarker levels as the outcome variable to compare two types of sites. The diagnostic accuracy of the biomarkers was evaluated by Youden's index to estimate the sensitivity, specificity and the area under curve (AUC). RESULTS: The levels of MMP-1, MMP-2, MMP-3, OPN, and TSLP were higher at sites with periodontitis and peri-implantitis compared to the levels at sites with healthy teeth and healthy implants. No significant differences were observed in the levels of the measured markers between the sites diagnosed with periodontitis and those diagnosed with peri-implantitis. The highest diagnostic potential at implant sites was found for MMP-2 (AUC = 0.74) and TSLP (AUC = 0.72). The highest AUC (0.82) at tooth sites was found for OPN. CONCLUSIONS: The findings indicate that the proteolytic enzyme MMP-2 and the cytokine TSLP might be potential biomarkers for both periodontitis and peri-implantitis, whereas the proinflammatory cytokine OPN may serve as a biomarker for periodontitis. Further studies are required to confirm the utility of these biomarkers and explore their potential clinical applications.

Microbiome of periodontitis and peri-implantitis before and after therapy: Long-read 16S rRNA gene amplicon sequencing.

AIMS: The microbial profiles of peri-implantitis and periodontitis (PT) are inconclusive. The controversies mainly arise from the differences in sampling sites, targeted gene fragment, and microbiome analysis techniques. The objective of this study was to explore the microbiomes of peri-implantitis (PI), control implants (CI), PT and control teeth (CT), and the microbial change of PI after nonsurgical treatment (PIAT). METHODS: Twenty-two patients diagnosed with both PT and peri-implantitis were recruited. Clinical periodontal parameters and radiographic bone levels were recorded. In each patient, the subgingival and submucosal plaque samples were collected from sites with PI, CI, PT, CT, and PIAT. Microbiome diversity was analyzed by high-throughput amplicon sequencing using full-length of 16S rRNA gene by next generation sequencing. RESULTS: The 16S rRNA gene sequencing analysis revealed 512 OTUs in oral microbiome and 377 OTUs reached strain levels. The PI and PT groups possessed their own unique core microbiome. Treponema denticola was predominant in PI with probing depth of 8-10 mm. Interestingly, Thermovirga lienii DSM 17291 and Dialister invisus DSM 15470 were found to associate with PI. Nonsurgical treatment for peri-implantitis did not significantly alter the microbiome, except Rothia aeria. CONCLUSION: Our study suggests Treponemas species may play a pivotal role in peri-implantitis. Nonsurgical treatment did not exert a major influence on the peri-implantitis microbiome in short-term follow-up. PT and peri-implantitis possess the unique microbiome profiles, and different therapeutic strategies may be suggested in the future.

Disease recurrence during supportive therapy following peri-implantitis treatment: A retrospective study.

AIM: Supportive therapy is key to prevent disease recurrence after peri-implantitis treatment. The primary objective was to quantify disease recurrence during supportive peri-implant therapy (SPIT) after peri-implantitis treatment. A secondary objective was to assess the success/failure of cumulative interceptive supportive therapy (CIST) after peri-implantitis treatment. METHODS: Compliers (whether regular or erratic) with SPIT after peri-implantitis treatment during ≥12 months were retrospectively evaluated. CIST was prescribed whenever residual pockets ≥6 mm concomitant with profuse bleeding on probing (disease recurrence) were identified. Patient- and implant-related factors were analyzed to explore their associations with disease recurrence and the need for CIST. RESULTS: Disease recurrence was considered in 28 patients (40 implants). Of these, 14 patients (23 implants) further demonstrated radiographic evidence of progressive bone loss (≥1 mm). This represented an overall disease recurrence following peri-implantitis treatment of ~20% and ~ 10% at patient and implant levels, respectively. Smokers, patients diagnosed at baseline with periodontitis grade C, and males were significantly more prone to exhibit recurrence. Patients undergoing CIST due to instability were not likely to respond favorably (~70% continued to exhibit residual pockets). CONCLUSION: Disease recurrence during SPIT following peri-implantitis treatment on selected cases is ~20%. Patients undergoing CIST due to instability are not likely to respond favorably.

Potential role of metal nanoparticles in treatment of peri-implant mucositis and peri-implantitis.

Peri-implantitis (PI), a pathological condition associated with plaque, affects the tissues around dental implants. In addition, peri-implant mucositis (PIM) is a precursor to the destructive inflammatory PI and is an inflammation of the soft tissues surrounding the dental implant. It is challenging to eradicate and regulate the PI treatment due to its limited effectiveness. Currently, there is a significant interest in the development and research of additional biocompatible materials to prevent the failure of dental implants. Nanotechnology has the potential to address or develop solutions to the significant challenge of implant failure caused by cytotoxicity and biocompatibility in dentistry. Nanoparticles (NPs) may be used as carriers for the release of medicines, as well as to make implant coatings and supply appropriate materials for implant construction. Furthermore, the bioactivity and therapeutic efficacy of metal NPs in peri-implant diseases (PID) are substantiated by a plethora of in vitro and in vivo studies. Furthermore, the use of silver (Ag), gold (Au), zinc oxide, titanium oxide (TiO2), copper (Cu), and iron oxide NPs as a cure for dental implant infections brought on by bacteria that have become resistant to several medications is the subject of recent dentistry research. Because of their unique shape-dependent features, which enhance bio-physio-chemical functionalization, antibacterial activity, and biocompatibility, metal NPs are employed in dental implants. This study attempted to provide an overview of the application of metal and metal oxide NPs to control and increase the success rate of implants while focusing on the antimicrobial properties of these NPs in the treatment of PID, including PIM and PI. Additionally, the study reviewed the potential benefits and drawbacks of using metal NPs in clinical settings for managing PID, with the goal of advancing future treatment strategies for these conditions.

Ebselen restores peri-implantitis-induced osteogenic inhibition via suppressing BMSCs ferroptosis.

It is hard to reconstruct bone defects in peri-implantitis due to osteogenesis inhibited by excessive reactive oxygen species (ROS). Ferroptosis, a recently identified regulated cell death characterized by iron- and ROS- dependent lipid peroxidation, provides us with a new explanation. Our study aims to explore whether ferroptosis is involved in peri-implantitis-inhibited osteogenesis and confirm ebselen, an antioxidant with glutathione peroxidase (GPx)-like activity, could inhibit ferroptosis and promote osteogenesis in peri-implantitis. In this study, we used LPS to mimic the microenvironment of peri-implantitis. The osteogenic differentiation of bone-marrow-derived mesenchymal stem cells (BMSCs) was assessed by alkaline phosphatase (ALP), Alizarin Red S, and mRNA and protein expression of osteogenic-related markers. Ferroptosis index analysis included iron metabolism, ROS production, lipid peroxidation and mitochondrial morphological changes. Iron overload, reduced antioxidant capability, excessive ROS, lipid peroxidation and the characteristic mitochondrial morphological changes of ferroptosis were observed in LPS-treated BMSCs, and adding Ferrostatin-1 (Fer-1) restored the inhibitory effect of ferroptosis on osteogenic differentiation of BMSCs. Furthermore, ebselen ameliorated LPS-induced ferroptosis and osteogenic inhibition, which were reversed by erastin. Our results demonstrated that ferroptosis is involved in osteogenic inhibition in peri-implantitis and ebselen could attenuate osteogenic dysfunction of BMSCs via inhibiting ferroptosis.

Treatment of peri-implantitis with a flapless surgical access combined with implant surface decontamination and adjunctive systemic antibiotics: A retrospective case series study.

AIM: To evaluate the effectiveness of a flapless surgical approach in the treatment of peri-implantitis and to explore the factors influencing its outcome. MATERIALS AND METHODS: The present retrospective study evaluated patients with at least one implant diagnosed with peri-implantitis and treated with a flapless surgical access, with or without systemic antimicrobials, curettage and, when needed, prostheses modification. Clinical and radiographic parameters were assessed at baseline and at 3 months and at least 12 months. The primary outcome was disease resolution (≤1 bleeding sites, probing depth [PD] ≤5 mm, no bone loss >0.5 mm). Multilevel regression analyses were used to identify predictors influencing the probability of attaining disease resolution. RESULTS: One hundred and seventeen patients with 338 implants were included. Disease resolution was attained in 54.4% of the 338 implants receiving flapless surgical access. At the end of the follow-up period, 111 patients (94.9%) with 295 implants (87.3%) did not require any further treatment, with 81.4% of these implants presenting PD ≤ 5 mm. History of periodontitis and PD at baseline were identified as negative predictors, while compliance with supportive peri-implant care, a machined surface and the adjunctive use of systemic azithromycin or metronidazole were identified as positive predictive factors for disease resolution. CONCLUSIONS: A flapless surgical approach led to disease resolution in 54.4% of the implants with peri-implantitis. Several risk/protective predictors for disease resolution were identified.

Systemic antibiotics in the surgical treatment of peri-implantitis: A randomized placebo-controlled trial.

AIM: To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics. MATERIALS AND METHODS: Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis. RESULTS: A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups. CONCLUSIONS: Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.

Diabetes mellitus exacerbates inflammation in a murine model of ligature-induced peri-implantitis: A histological and microtomographic study.

AIM: To investigate the influence of diabetes mellitus (DM) in a murine model of peri-implantitis (PI). MATERIALS AND METHODS: Twenty-seven 4-week-old C57BL/6J male mice had their first and second maxillary left molars extracted. Eight weeks later, one machined implant was placed in each mouse. Four weeks after osseointegration, the mice were divided into three groups: (a) control (C), (b) PI and (c) DM + PI. DM was induced by streptozotocin (STZ) administration. After DM induction, PI was induced using ligatures for 2 weeks. The hemimaxillae were collected for micro-CT and histological analyses. The primary outcomes consisted of linear (mm) and volumetric (mm3) bone loss. Secondary outcomes were based on histological analysis and included inflammatory infiltrate, osteoclastic activity, matrix organization, composition and remodelling. Data are presented as means ± SEM. Statistical analyses were performed using one-way ANOVA, followed by Tukey's test. RESULTS: Gingival tissue oedema was detected in the PI and DM + PI groups. Micro-CT showed significantly increased linear and volumetric bone loss in the DM + PI group compared to the C and PI groups. H&E staining showed greater inflammatory response and bone resorption in the PI and DM + PI groups than in the C group. The DM + PI group had significantly higher osteoclast numbers than the C and PI groups. Picrosirius red stained less for types I and III collagen in the PI and DM + PI groups than in the C group. There was a significant increase in monocyte/macrophage (CD-11b) counts and matrix metalloproteinases (MMP-2 and MMP-8) marker levels and a significant decrease in the matrix metalloproteinases inhibition marker (TIMP-2) levels in the DM + PI group compared to the C and PI groups. CONCLUSIONS: DM exacerbates PI-induced soft-tissue inflammation, matrix degradation and bone loss.

Single-cell analysis reveals a unique microenvironment in peri-implantitis.

AIM: This study aimed to reveal the unique microenvironment of peri-implantitis through single-cell analysis. MATERIALS AND METHODS: Herein, we performed single-cell RNA sequencing (scRNA-seq) of biopsies from patients with peri-implantitis (PI) and compared the results with healthy individuals (H) and patients with periodontitis (PD). RESULTS: Decreased numbers of stromal cells and increased immune cells were found in the PI group, which implies a severe inflammatory infiltration. The fibroblasts were found to be heterogeneous and the specific pro-inflammatory CXCL13+ sub-cluster was more represented in the PI group, in contrast to the PD and H groups. Furthermore, more neutrophil infiltration was detected in the PI group than in the PD group, and cell-cell communication and ligand-receptor pairs revealed most neutrophils were recruited by CXCL13+ fibroblasts through CXCL8/CXCL6-CXCR2/CXCR1. Notably, our study demonstrated that the unique microenvironment of the PI group promoted the differentiation of monocyte/macrophage lineage cells into osteoclasts, which might explain the faster and more severe bone resorption in the progression of PI than PD. CONCLUSIONS: Collectively, this study suggests a unique immune microenvironment of PI, which may explain the differences between PI and PD in the clinic. These outcomes will aid in finding new specific and effective treatments for PI.

Single-cell sequencing identifies inflammation-promoting fibroblast-neutrophil interaction in peri-implantitis.

AIM: To reveal the cellular composition and molecular environment of the periodontal and peri-implant inflammatory infiltrates through a single-cell sequencing technique, which may explain the pathological difference between these two diseases. A special focus was placed on the phenotypes and potential roles of neutrophils and fibroblasts in peri-implant/periodontal tissue immunity. MATERIALS AND METHODS: High-throughput single-cell transcriptomic profiling of peri-implant tissues from patients with peri-implantitis as well as periodontal tissues from patients with periodontitis and healthy donors was performed. Immunofluorescence analysis was carried out to further validate the identified cell subtypes and their involvement in peri-implantitis and periodontitis. RESULTS: Based on our single-cell resolution analysis, a quantified proportional increase of neutrophil (Neu) subtypes was shown in peri-implantitis. Among these, a predominance of Neutro_CXCR2 was revealed. We also found the involvement of inflammation-promoting fibroblasts as well as a predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction in peri-implantitis. CONCLUSIONS: Our study indicated that the predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction might underline the enhanced host response in peri-implantitis compared with periodontitis. This information offers a molecular basis by which fibroblast and neutrophil subtypes might be diagnostically and therapeutically targeted in peri-implantitis.

The efficacy of reconstructive therapy in the surgical management of peri-implantitis: A 3-year follow-up of a randomized clinical trial.

AIM: To assess whether guided bone regeneration (GBR) treatment of peri-implantitis-related bony defects could improve healing compared to open flap debridement (OFD) at 36 months. MATERIALS AND METHODS: In a multi-centre, randomized clinical trial, 32 individuals received OFD (control group [CG]) and 34 GBR treatment (test group [TG]). Radiographic defect fill (RDF), probing pocket depth (PPD), bleeding on probing (BOP) suppuration (SUP), mucosal recession (MREC) and patient-reported outcomes (PROs) were evaluated at 36 months. RESULTS: Fifty individuals attended a supportive peri-implant therapy program and completed the 36-month follow-up. GBR treatment resulted in an RDF of 2.13 ± 1.26 mm compared to 1.64 ± 1.54 mm following OFD (p = .18). No difference was found in PPD, BOP, SUP, REC or PROs between the groups. Successful treatment (no additional bone loss, PPD ≤ 5 mm, no BOP and no SUP) was achieved in 46.2% in TG and 20% in CG (p = .053). Treatment results obtained at 12 months were generally maintained up to 36 months. No significant changes were noticed between 12 and 36 months. CONCLUSIONS: At 36 months, treatment results obtained at 1 year were sustained following both GBR and OFD in patients attending supportive peri-implant therapy. GBR resulted in more RDF and higher composite treatment success rate than OFD (ClinicalTrials.gov Identifier [NCT02375750]).