Experimental Peri-implantitis Research Articles

Induction of Experimental Peri-Implantitis with Strains Selected from the Human Oral Microbiome.

Peri-implantitis (PI), the most widespread condition in the oral cavity, affects patients globally; thus, advanced research in both in vitro and in vivo studies is required. This study aimed to develop peri-implantitis in the rat model by oral contamination with bacteria responsible for PI in humans. The study was carried out in three stages: the extraction of the maxillary first molar to reproduce the human edentation, the mounting of the implant, and finally, the contamination of the device by gavage with Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus oralis. The hematological examinations showed statistically significant increases for WBCs (white blood cells), Hb (hemoglobin), RBCs (red blood cells), MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration), and PLTs (platelets), but especially for the level of neutrophils and lymphocytes, and the systemic immunoinflammatory index completed the picture related to the inflammatory response triggered as a result of the activity of microorganisms pathogens on oral tissues. By examining the liver and kidney profile, we hypothesized that peri-implantitis is associated with systemic diseases, and the histopathological examination showed peri-implantitis lesions characterized by a marked inflammatory infiltrate with numerous neutrophils and lymphocytes. By corroborating all the results, we successfully developed a rat peri-implantitis model using a mixed bacterial infection through the oral gavage technique.

Peri-implantitis increases the risk of medication-related osteonecrosis of the jaws associated with osseointegrated implants in rats treated with zoledronate

This study evaluated the peri-implant tissues under normal conditions and under the influence of experimental peri-implantitis (EPI) in osseointegrated implants installed in the maxillae of rats treated with oncologic dosage of zoledronate. Twenty-eight senescent female rats underwent the extraction of the upper incisor and placement of a titanium dental implant (DI). After eight weeks was installated a transmucosal healing screw on DI. After nine weeks, the following groups were formed: VEH, ZOL, VEH-EPI and ZOL-EPI. From the 9th until the 19th, VEH and VEH-EPI groups received vehicle and ZOL and ZOL-EPI groups received zoledronate. At the 14th week, a cotton ligature was installed around the DI in VEH-EPI and ZOL-EPI groups to induce the EPI. At the 19th week, euthanasia was performed, and the maxillae were processed so that at the implanted sites were analyzed: histological aspects and the percentage of total bone tissue (PTBT) and non-vital bone tissue (PNVBT), along with TNFα, IL-1β, VEGF, OCN and TRAP immunolabeling. ZOL group presented mild persistent peri-implant inflammation, higher PNVBT and TNFα and IL-1β immunolabeling, but lower for VEGF, OCN and TRAP in comparison with VEH group. ZOL-EPI group exhibited exuberant peri-implant inflammation, higher PNVBT and TNFα and IL-1β immunolabeling when compared with ZOL and VEH-EPI groups. Zoledronate disrupted peri-implant environment, causing mild persistent inflammation and increasing the quantity of non-vital bone tissue. Besides, associated with the EPI there were an exacerbated inflammation and even greater increase in the quantity of non-vital bone around the DI, which makes this condition a risk factor for medication-related osteonecrosis of the jaws.

CCR2 is a potential therapeutic target in peri-implantitis.

CCR2 (C-C chemokine receptor type 2) plays a crucial role in inflammatory and bone metabolic diseases; however, its role in peri-implantitis remains unclear. This study aimed to explore whether CCR2 contributes to peri-implantitis and the treatment effects of cenicriviroc (CVC) on peri-implant inflammation and bone resorption. The expression of CCR2 was studied using clinical tissue analysis and an in vivo peri-implantitis model. The role of CCR2 in promoting inflammation and bone resorption in peri-implantitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC on peri-implantitis was evaluated using systemic and local dosage forms. Human peri-implantitis tissues showed increased CCR2 and CCL2 levels, which were positively correlated with bone loss around the implants. Knocking out Ccr2 in an experimental model of peri-implantitis resulted in decreased monocyte and macrophage infiltration, reduced pro-inflammatory cytokine generation and impaired osteoclast activity, leading to reduced inflammation and bone loss around the implants. Treatment with CVC ameliorated bone loss in experimental peri-implantitis. CCR2 may be a potential target for peri-implantitis treatment by harnessing the immune-inflammatory response to modulate the local inflammation and osteoclast activity.

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

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. 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. 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). AdipoAI suppressed osteoclastogenesis in diabetes-associated peri-implantitis by inhibiting the NF-κB and Wnt5a-Ror2 pathways via the AdipoR1/APPL1 axis.

Influence of Section Thickness on the Accuracy and Specificity of Histometric Parameters Using Confocal Laser Scanning Microscopy in a Canine Model of Experimental Peri-Implantitis—A Proof of Concept

Tissue breakdown was assessed by confocal laser scanning microscopy (CLSM) using autofluorescence around implants with ligatures, on a dog hemimandible. Influence of section thickness on the accuracy of histometrical observations was also evaluated, in comparison with thin sections in light microscopy. Three months after tooth extraction, implants were placed. Two months after abutment placement, ligatures were placed with no plaque control. 11 months post-implantation, the animal was sacrificed. Undecalcified thin (30 µm) sections were cut, stained and evaluated by light microscopy to be used as a reference. Additional sections were performed, so that another pair of unstained thick sections resulted (250-300 µm). Tissue loss was assessed using histomorphometric parameters under CLSM and was compared to the light microscopy reference ones. Morphometry confirmed tissue loss more pronounced on the "thick" and quick sections, when compared to the time-consuming and technique-sensitive "thin" ones. Within the limits of the present study, the adequacy of histometrical observations under CLSM reveal commensurable information about soft-tissue-bone-implant details, when compared to traditional light microscopy histological protocols. The CLSM investigation may seem demanding, yet the richness of data acquired may justify this approach, provided seatbacks caused by improper manipulation of "thick" sections are avoided.

Progression of experimental peri-implantitis in guided bone regeneration and pristine bone: A preclinical in vivo study.

Guided bone regeneration (GBR) is the most widely used technique for overcoming the deficiency of alveolar bone. However, the progression of peri-implantitis in regenerative and pristine bone sites has not been fully investigated. The aim of this study is to compare experimental peri-implantitis around implants placed in pristine bone and GBR sites. Bilateral mandibular first molars were extracted from six beagle dogs, and standardized horizontal ridge defectwas simultaneously created at predetermined site in unilateral mandible. After 8weeks, guided bone regeneration procedure was conducted at the defect site. After 16 weeks, implants (ϕ 3.6×8.0mm) were placed at both extracted sites. This study included 3 months of active breakdown and another 3 months of spontaneous progression period. Radiographs were taken at each phase and specimens were obtained for histological, immunohistochemical, and polarized light microscopic analysis. Marginal bone loss around implant did not show the significant differences between pristine bone and GBR sites during spontaneous progression period. In immunohistochemical analysis, inflammatory and immune-related cells were predominantly detected in peri-implantitis-affected area rather than unaffected area. In the polarized light microscopic analysis, substantial reductions in the amount and thickness of collagen fibers were observed in peri-implantitis-affected area compared with unaffected tissues. However, there were no significant differences in histological, immunohistochemical, polarized light microscopic outcomes between pristine bone and GBR sites. Previous hard tissue grafting at the implant sites did not affect experimental peri-implantitis and exhibited similar radiographic, histological, immunohistochemical, and polarized light microscopic outcomes compared with those of pristine bone sites.

Histomorphometrical and CBCT Evaluation of Tissue Loss Progression Induced by Consecutive, Alternate Ligatures in Experimental Peri-Implantitis in a Dog Model: A Pilot Study.

Objectives: Soft and hard tissue breakdown was histologically and radiologically assessed around implants with alternate, consecutively placed ligatures on the same edentulous dog hemimandible. The influence of ligatured implants (LI) on adjacent non-ligatured implants (NLI, as a possible naturally induced peri-implantitis) was also evaluated. Material and Methods: Three months after tooth extraction, five dental implants were placed in the dog hemimandible. Two months after abutment placement, ligatures were placed subsequently two months apart on alternate implants, while both intermediate implants were left without ligatures. Ligatures were kept in place during the entire experiment, and no plaque control measures were taken. Eleven months post-implantation, the animal was sacrificed. Undecalcified ground sections were cut, stained with Masson Goldner and MOVAT Pentachrome and evaluated by light microscopy. Soft and hard tissue loss was assessed using histomorphometric and CBCT parameters. Results: All NLI presented deep false peri-implant pockets on the oral aspect and pronounced vertical bone resorption on the buccal aspect. After 2, 4 and 6 months, during the breakdown period, more than 30% of the bone was lost in LI in all directions, while, despite immediate vicinity, NLI displayed less destruction. Intense inflammation, typical for induced peri-implantitis, was present, with similar intensity in LI as NLI, but in different parts of the lesions. Morphometry confirmed intense soft tissue inflammation, more bone resorption and higher amounts of infiltrated connective tissue in LI when compared with NLI. Conclusion: Within the limits of the present pilot study, the adequacy of the experimental dog model based on ligature-induced peri-implantitis was able to be successfully challenged by non-ligature models of spontaneously occurring peri-implant inflammation, while meeting the requirements for experimental designs with a very small numbers of animals. The influence of implants with severe peri-implantitis on adjacent implants resulted in less than expected tissue loss in the latter accession numbers.

Excessive inflammatory response to infection in experimental peri-implantitis: Resolution by Resolvin D2.

The aetiology and pathogenesis of peri-implantitis are currently under active research. This study aimed to dissect the pathogenesis of murine experimental peri-implantitis and assess Resolvin D2 (RvD2) as a new treatment modality. Four weeks following titanium implant insertion, mice were infected with Porphyromonas gingivalis using single or multiple oral lavages. RvD2 was administrated following infection, and tissues were analysed using flow cytometry, quantitative RT-PCR, taxonomic profiling, and micro-computed tomography. Repeated infections with Pg resulted in microbial dysbiosis and a higher influx of innate and adaptive leukocytes to the peri-implant mucosa (PIM) than to gingiva surrounding the teeth. This was accompanied by increased expression levels of IFN-α, IL-1β, and RANKL\OPG ratio. Interestingly, whereas repetitive infections resulted in bone loss around implants and teeth, a single infection induced bone loss only around implants, suggesting a higher susceptibility of the implants to infection. Treatment with RvD2 prevented Pg-driven bone loss and reduced leukocyte infiltration to the PIM. Murine dental implants are associated with dysregulated local immunity and increase susceptibility to pathogen-induced peri-implantitis. However, the disease can be prevented by RvD2 treatment, highlighting the promising therapeutic potential of this treatment modality.

Surgical treatment of experimental peri-implantitis using mechanical and chemical decontamination procedures: A pre-clinical in vivo study.

To evaluate the effect of surgical treatment of experimental peri-implantitis at implants with different surface characteristics using mechanical and chemical decontamination methods. Following extraction of mandibular premolars, four implants with two different surface characteristics (A, moderately rough and B, smooth) were placed in each side of the mandible of six dogs. Experimental peri-implantitis was induced. Surgical treatment of the peri-implantitis sites was carried out using four implant surface decontamination protocols: (i) deposition of a citric acid gel, (ii) mechanical cleaning using a rotating titanium brush, (iii) a combination of the mechanical and chemical procedures, and (iv) saline (control). Clinical and radiographic examinations were performed. Block biopsies were obtained 6months after therapy and prepared for histological analysis. Irrespective of the treatment group, treatment resulted in 0.63 ± 0.92 and 0.65 ± 0.67 mm radiographic bone gain around implants A and B, respectively. Histological analyses revealed that persisting soft tissue inflammation as assessed using an infiltrated connective tissue (ICT) score was significantly lower at implant type B than at implant type A for all treatment groups. The test decontamination procedures did not demonstrate better results regarding resolution of peri-implantitis lesions, as indicated by the ICT scores, than the control procedure. The control treatment resulted in significantly superior outcomes of resolution of peri-implantitis lesions than the citric acid regimen. It is concluded that decontamination procedures including citric acid gel or rotating titanium brush did not improve outcomes following surgical treatment of experimental peri-implantitis. Results were, however, influenced by the implant surface characteristics.

Accuracy of bone-level assessments following reconstructive surgical treatment of experimental peri-implantitis.

AimsThe purpose of this study was to evaluate the accuracy of bone‐level assessments using either cone‐beam computed tomography (CBCT), intra‐oral peri‐apical (PA) radiographs or histology following reconstructive treatment of experimental peri‐implantitis.Materials and MethodsSix Labrador dogs were used. Experimental peri‐implantitis was induced 3 months after implant placement. Surgical treatment of peri‐implantitis was performed and peri‐implant defects were allocated to one of four treatment categories; no augmentation, bone graft materials with or without a barrier membrane. Six months later, intra‐oral PA radiographs and block biopsies from all implants sites were obtained. Marginal bone levels (MBLs) were measured using PA radiographs, CBCT and histology.ResultsSignificant correlations of MBL assessments were observed between the three methods. The measurements in PA radiographs consistently resulted in an overestimation of the bone level of about 0.3–0.4 mm. The agreement between the methods was not influenced by the use of bone substitute materials in the management of the osseous defects.ConclusionsAlthough MBL assessments obtained from PA radiographs showed an overestimation compared to MBL assessments on corresponding CBCT images and histological sections, PA radiographs can be considered a reliable technique for peri‐implant bone‐level evaluations following reconstructive surgical therapy of experimental peri‐implantitis.

Rodent peri-implantitis models: a systematic review and meta-analysis of morphological changes.

Rodent models have emerged as an alternative to established larger animal models for peri-implantitis research. However, the construct validity of rodent models is controversial due to a lack of consensus regarding their histological, morphological, and biochemical characteristics. This systematic review sought to validate rodent models by characterizing their morphological changes, particularly marginal bone loss (MBL), a hallmark of peri-implantitis. This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A literature search was performed electronically using MEDLINE (PubMed), and Embase, identifying pre-clinical studies reporting MBL after experimental peri-implantitis induction in rodents. Each study's risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool. A meta-analysis was performed for the difference in MBL, comparing healthy implants to those with experimental peri-implantitis. Of the 1,014 unique records retrieved, 23 studies that met the eligibility criteria were included. Peri-implantitis was induced using 4 methods: ligatures, lipopolysaccharide, microbial infection, and titanium particles. Studies presented high to unclear risks of bias. During the osseointegration phase, 11.6% and 6.4%-11.3% of implants inserted in mice and rats, respectively, had failed to osseointegrate. Twelve studies were included in the meta-analysis of the linear MBL measured using micro-computed tomography. Following experimental peri-implantitis, the MBL was estimated to be 0.25 mm (95% confidence interval [CI], 0.14-0.36 mm) in mice and 0.26 mm (95% CI, 0.19-0.34 mm) in rats. The resulting peri-implant MBL was circumferential, consisting of supra- and infrabony components. Experimental peri-implantitis in rodent models results in circumferential MBL, with morphology consistent with the clinical presentation of peri-implantitis. While rodent models are promising, there is still a need to further characterize their healing potentials, standardize experiment protocols, and improve the reporting of results and methodology. PROSPERO Identifier: CRD42020209776.

Influence of Different Implant Types on Bone Levels After Healing and Peri-implant Tissue Reactions Following Peri-implantitis: A Preclinical Study.

This study evaluated the influence of different implant types on (1) radiographic marginal bone levels after healing and (2) radiographic and histomorphometric tissue levels and characteristics following ligature-induced peri-implantitis. Four implant types (Standard Plus, Straumann [S]; NobelReplace Tapered, Nobel Biocare [N]; In-Kone Universal, Global D [I]; and twinKon, Global D [T]) were randomly placed in the edentulous healed mandibular ridge of six dogs (T0), for a total of 57 implants placed. After 10 weeks, a peri-implantitis was ligature-induced (T1). After 12 weeks, biopsy samples were processed for histomorphometric analysis (T2). Standardized radiographs were taken at T0, T1, and T2 for imaging analysis. Statistical analysis was performed using mixed-effects linear modeling. After healing (T1), the radiographic marginal bone level was more coronal for implants I, T, and S compared to N. Following peri-implantitis (T2), the histologic marginal bone level was more coronal for implants I, T, and S compared to N, and for implants I and T compared to S. Also at T2, the radiographic marginal bone level was more coronal at implants I, T, and S compared to N. Implant type may influence bone remodeling during healing and bone loss during the early stages of experimental peri-implantitis.

Glycemic fluctuation exacerbates inflammation and bone loss and alters microbiota profile around implants in diabetic mice with experimental peri-implantitis

BackgroundThe impact of glycemic fluctuation under diabetic condition on peri-implantitis in diabetic patients remains unclear. We hypothesized that glycemic fluctuation has greater adverse effect on experimental peri-implantitis, compared with sustained high blood glucose in diabetes.ResultsMaxillary left first and second molars of diabetic db/db mice were extracted and were replaced with one dental implant in the healed edentulous space. Glycemic control or fluctuation were managed by constant or interrupted oral administration of rosiglitazone to these mice. Meanwhile, experimental peri-implantitis was induced by ligation around implants. After 14 weeks, inflammatory responses, and peri-implant bone loss, together with oral microbiota profile were analyzed. Diabetic mice with glycemic fluctuation showed greater peri-implant bone loss, inflammatory cell infiltration, and osteoclastogenesis, compared with mice with sustained hyperglycemia. Compared to sustained hyperglycemia, glycemic fluctuation led to further increase in IL-1β, TNFα, RANKL, TLR2/4, IRAK1, and TRAF6 mRNA expression in peri-implant gingival tissues. Both rosiglitazone-induced glycemic control and glycemic fluctuation caused microbiota profile change in diabetic mice compared to that in uncontrolled hyperglycemic mice.ConclusionsThis study suggests that glycemic fluctuation may aggravate peri-implantitis inflammation and bone loss, which may be associated with a shift in peri-implant microbial profile towards dysbiotic changes and the activation of TLR2/4-IRAK1-TRAF6 signaling.

Changes in the microcirculation in periodontal tissue due to experimental peri-implantitis

ObjectivesPeri-implantitis causes dislodgement of dental implants due to inflammation in the peri-implant tissue. The microcirculation in the periodontal tissue undergoes morphological and physiological changes due to inflammation. The immune mechanism of peri-implantitis differs from that of periodontitis. In this study, we examined the changes in the microcirculation in the peri-implant tissue with experimentally induced inflammation, using morphological and physiological techniques. MethodsSix beagle dogs were used in the experiment. After extracting both mandibular premolars, three titanium screw implants were inserted on each side of the mandibular jaw. Dental floss was placed on the right side for 90 days in the study group but not in the control group. Microvascular resin cast models were created, and morphological changes were observed using scanning electron microscopy. Periodontal blood flow was measured using laser Doppler flowmetry. ResultsNinety days after induction of inflammation, bone resorption was observed around the implant body. Osseointegration was impaired, and a gap at the implant–bone interface was observed. The resin cast models showed that inflamed gingival blood vessels had invaded the bone marrow through the resorbed apical margin of the alveolar bone. Analysis of the physiological data obtained using laser Doppler flowmetry showed a significant increase in blood flow around the implants with experimentally induced inflammation. ConclusionsSignificant morphological and physiological changes occur in the gingival microcirculation of peri-implant tissue due to inflammation. Evaluating the vasculature and blood flow in the tissue surrounding the site of peri-implantitis may be helpful for pathologic analysis in clinical settings.

Hard tissue volumetric and soft tissue contour linear changes at implants with different surface characteristics after experimentally induced peri-implantitis: an experimental in vivo investigation.

To evaluate the hard tissue volumetric and soft tissue contour linear changes in implants with two different implant surface characteristics after a ligature-induced peri-implantitis. In eight beagle dogs, implants with the same size and diameter but distinct surface characteristics were placed in the healed mandibular sites. Test implants had an external monolayer of multi-phosphonate molecules (B+), while control implants were identical but without the phosphonate-rich surface. Once the implants were osseointegrated, oral hygiene was interrupted and peri-implantitis was induced by placing subgingival ligatures. After 16weeks, the ligatures were removed and peri-implantitis progressed spontaneously. Bone to implant contact (BIC) and bone loss (BL) were assessed three-dimensionally with Micro-Ct (μCT). Dental casts were optically scanned and the obtained digitalized standard tessellation language (STL) images were used to assess the soft tissue vertical and horizontal contour linear changes. Reduction of the three-dimensional BIC percentage during the induction and progression phases of the experimental peri-implantitis was similar for both the experimental and control implants, without statistically significant differences between them. Soft tissue analysis revealed for both implant groups an increase in horizontal dimension after the induction of peri-implantitis, followed by a decrease after the spontaneous progression period. In the vertical dimension, a soft tissue dehiscence was observed in both groups, being more pronounced at the buccal aspect. The added phosphonate-rich surface did not provide a more resistant environment against experimental peri-implantitis, when assessed by the changes in bone volume and soft tissue contours. Ligature-induced peri-implantitis is a validated model to study the tissue changes occurring during peri-implantitis. It was hypothesized that a stronger osseointegration mediated by the chemical bond of a phosphonate-rich implant surface would develop an environment more resistant to the inflammatory changes occurring after experimental peri-implantitis. These results, however, indicate that the hard and soft tissue destructive changes occurring at both the induction and progression phases of experimental peri-implantitis were not influenced by the quality of osseointegration.

Experimental peri-implantitis around titanium implants with a chemically modified surface with a monolayer of multi-phosphonate molecules: a preclinical in vivo investigation.

The purpose of this experimental in vivo investigation was to evaluate the influence of modifying the implant surface by adding a monolayer of multi-phosphonate molecules on the development of experimental peri-implantitis. Eight beagle dogs received 5 tests and 5 control implants each following a split-mouth design 3months after premolar and molar extraction. On the most mesial implant of each side, a 3-mm buccal dehiscence was artificially created. Experimental peri-implantitis was induced by silk ligatures over a 4-month period; after ligature removal, peri-implantitis was left to progress for another 4months without plaque control. Clinical, histological, and radiographic outcomes were evaluated. Radiographically, both implant groups showed a similar bone loss (BL) at the end of the induction and progression phases. BL measured on the histological sections of the test and control groups was 3.14 ± 0.42mm and 3.26 ± 0.28mm, respectively; the difference was not statistically significant (p > 0.05). The remaining buccal bone to implant contact (bBIC) percentage of the test and control groups was 59.38 ± 18.62 and 47.44 ± 20.46%, respectively; the difference, however, was not statistically significant (p > 0.05). Bone loss observed at dehiscent sites compared to non-dehiscent ones showed no statistically significant difference (p > 0.05). Addition of a monophosphonate layer to a moderately rough implant surface did not affect development of experimental peri-implantitis. Influence of implant surface on peri-implantitis may condition implant selection by the clinician, especially on patients with disease risk factors. In that sense, monophosphate layer implants do not show higher peri-implantitis risk than control implants.

Influence of preformed bone defects on key pathogens and bone loss during experimental peri-implantitis formation in a canine model.

To determine the impact of experimentally preformed peri-implant crater-shaped bone defects on the evolution of in situ microbiota and development of bone defects compared to those induced over time by ligature placement only. Implants were installed in the mandibles of eight dogs. Standardized bone defects were preformed in four test animals but not in the other four control animals, prior to implant (3.3 mm × 8 mm) installation. After 2 months of healing, peri-implantitis was induced with silk ligatures in both groups for 2 months. Microbial samples were obtained from implants and teeth for analysis at three time points (qPCR), and the average depths of the bone defects were measured. At the baseline, the total marker load of periodontal-pathogenic bacteria (TML) for teeth accounted for 5.2% (0-17.4%). After implant healing, TMLs for implants and teeth were comparable (7.1% [0.3-17.4%]). The TML of both groups was 3.5%, 2 months after ligature placement. Bone defects had a mean depth of 1.84 mm at preformed defects and 1.64 mm at control sites (P > 0.05). Preformed defects in the test group showed comparable results to the control group in terms of TML, the incidence of periodontal-pathogenic bacteria, and bone defect depth.

Retraction: Yu, X., Hu, Y., Freire, M., Yu, P., Kawai, T., Han X. (2017) Role of toll-like receptor 2 in inflammation and alveolar bone loss in experimental peri-implantitis versus periodontitis. Journal of Periodontal Research 53(1), 98-106. https://doi.org/10.1111/jre.12492.

The above article, published online on 05 September 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal's Editor-in-Chief, Dr. Shinya Murakami, and John Wiley & Sons A/S. The retraction has been agreed as the Institutional Animal Care and Use Committee (IACUC) approval for the experimental peri-implantitis procedure used in this article was still pending at the time that the procedure was performed. The IACUC approval for the peri-implantitis procedure was received in 2017 after the article had been submitted. Although all the research design, methods, and results are valid, IACUC approval was not received at the time the research was performed, which is a requirement for all research submitted to the journal. The authors have agreed to retract the article.

Induced Experimental Peri-Implantitis and Periodontitis: What Are the Differences in the Inflammatory Response?

This preliminary study investigates the differences between experimental periodontitis and peri-implantitis in a dog model, with a focus on the histopathology, inflammatory responses, and specific immunoregulatory activities driven by Th1/Th2-positive cells. Twelve dental implants were inserted into the edentulated posterior mandibles of 6 beagle dogs and were given 12 weeks for osseointegration. Experimental peri-implantitis and periodontitis (first mandible molar) were then induced using cotton-floss ligatures. Twelve weeks later, alveolar bones were quantitated by cone beam-computer tomography. Histopathologic analysis of the inflamed gingiva and periodontal tissues was performed by light microscopy, and the Th1/Th2 cell populations were investigated by flow cytometry. Peri-implantitis and periodontitis were both found to be associated with pronounced bone resorption effects, both to a similar degree vertically, but with a differential bone resorption pattern mesio-distally, and with a significantly higher and consistent bone resorption result in peri-implantitis, although with a higher variance of bone resorption in periodontitis. The histologic appearances of the inflammatory tissues were identical. The percentages of Th1/Th2 cells in the inflamed gingival tissues of both experimental peri-implantitis and periodontitis were also found to be similar. Experimental periodontitis and peri-implantitis in the dog model show essentially the same cellular pathology of inflammation. However, bone resorption was found to be significantly higher in peri-implantitis; the histopathologic changes in the periodontal tissues were similar in both groups but showed a higher interindividual variation in periodontitis and appeared more uniform in peri-implantitis. This preliminary study indicates that more focused experimental in vivo inflammation models need to be developed to better simulate the human pathology in the 2 different diseases and to have a valuable tool to investigate more specifically how novel treatments/prevention approaches may heal the differential adverse effects on bone tissue and on periodontium in periodontitis and in periimplantitis.

Differences in the progression of experimental peri-implantitis depending on the implant to abutment connection.

The aim was to evaluate the rate of bone loss progression during experimentally induced peri-implantitis using two different implant-abutment connections in implants with identical surface topography. Forty-eight Regular Neck tissue-level SLA implants with a matching implant to abutment connection (TL) and 36 bone-level SLA implants with a switching platform implant to abutment connection (BL) were subjected to experimental peri-implantitis in two independent in vivo pre-clinical investigations. Experimental peri-implantitis was induced by means of silk ligatures during 3 months (induction phase), and followed for one extra month without ligatures (progression phase). Radiographic and clinical outcomes were evaluated longitudinally along both studies and subsequently compared between experiments. During the induction phase, radiographic bone loss was significantly higher in implants with matched abutments compared with those with platform switching connections (2.65 ± 0.66 mm vs 0.84 ± 0.16 mm, respectively, p = 0.001). During the progression phase, both types of implant-abutment connection exhibited similar rates of radiographic bone loss. Similar outcomes were observed clinically. A platform switching connection resulted in a more benign development of peri-implantitis during the experimental induction phase of the disease. These differences, however, disappeared once the ligatures were removed (progression phase). Influence of the implant-abutment connection in peri-implantitis progression may be relevant when considering implant selection in the moment of placement. In this sense, platform switching abutment demonstrated less peri-implantitis development when compared to implant matching connection.