Ligature-induced Peri-implantitis Research Articles

Peri-Implant Microbial Signature Shifts in Titanium, Zirconia and Ceria-Stabilized Zirconia Reinforced with Alumina Sites Subjected to Experimental Peri-Implantitis: A Preclinical Study in Dogs.

This study evaluates the dynamic shift in the microbiota at the peri-implant site of titanium (Ti) and zirconia (Zr) implants subjected to experimental peri-implantitis (PI) and, for the first time, of implants made of ceria-stabilized alumina-reinforced zirconia (Ce-TZP/Al), a revolutionary zirconia that is set to play a key role in modern implant dentistry. One- and two-piece (TP) implants, including Ce-TZP/AL TP/G3 glass, were placed bilaterally (six implants/side) in five beagle dogs to mimic a natural vs. ligature-induced PI following a split-mouth design. The experiment spanned 30 weeks from tooth extraction. Both PI models promoted plaque deposition at peri-implant sites. Comparatively, the PI induced by ligatures favored the deposition of anaerobes (p = 0.047 vs. natural). Regardless of the model, the plaque deposition pattern was entirely dependent on the implanted material. Ligated Ti and Zr implant sites accumulated up to 2.14 log CFU/mL unit anaerobic load (p ≤ 0.033 vs. non-ligated implant sites), predominantly comprising obligate anaerobes. Naturally occurring PI induced the deposition of co-occurring networks of obligate anaerobes and less oxygen-dependent bacteria. PI induction favored the enrichment of Ti and Zr sites with bacterial taxa belonging to the orange and red complexes (up to 28% increase naturally and up to 71% in the ligated hemiarch). Anaerobic deposition was significantly lower in ligated Ce-TZP/Al implant sites (p ≤ 0.014 vs. TI and Zr) and independent of the induction model (0.63-1 log units of increase). Facultative bacteria prevailed at Ce-TZP/AL sites. The abundance was lower in the Ce-TZP/AL TP implant. Unlike Ti and Zr sites, taxa from the orange and red complexes were negligible. Biofilms configured at the Ti and Zr sites after ligation-induced PI resemble those found in severe IP. We hypothesize that, although surface properties (surface energy and surface roughness) and physicochemical properties of the substrate play an important role in bacterial adhesion and subsequent plaque formation, Ce-TZP/Al modulates several biological activities that preserve the integrity of the gingival seal by limiting PI progression. In conclusion, biofilm progression differs in peri-implant sites according to the specific properties of the material. Ce-TZP/A, unlike titanium or zirconia, prevents dysbiosis in sites subjected to experimental PI and preserves the microbial signature of emergent obligate anaerobes related to PI development.

Impact of surface chemical treatment in surgical regenerative treatment of ligature-induced peri-implantitis: A canine study.

Implant surface decontamination is a critical step in peri-implantitis treatment. The aim of this study was to assess the effect chemotherapeutic agents have on reosseointegration after treatment on ligature-inducted peri-implantitis. Six male canines had 36 implants placed and ligatures were placed around them for 28 weeks to establish peri-implantitis. The peri-implant defects were randomly treated by 1 of 3 methods: 0.12% chlorhexidine (CHX test group), 1.5% sodium hypochlorite (NaOCl test group), or saline (Control group). Sites treated with NaOCl and CHX were grafted with autogenous bone, and all sites then either received a collagen membrane or not. Histology sections were obtained at 6 months postsurgery to assess percentage of reosseointegration. Thirty-five implants were analyzed (CHX: 13; NaOCl: 14; Control:8). NaOCl-treated sites demonstrated reosseointegration with direct bone-to-implant-contact on the previously contaminated surfaces (42% mean reosseointegration), which was significantly higher than Controls (p<0.05). Correspondingly, clinical improvement was noted with a significant reduction in probing depth from 5.50±1.24mm at baseline to 4.46±1.70mm at 6-months postsurgery (p=0.006). CHX-treated sites demonstrated a nonsignificant reosseointegration of 26% (p>0.05); however, in the majority of cases, the new bone growth was at a distance from the implant surface without contact. Probing depths did not improve in the CHX group. The use of membrane did not influence reosseointegration or probing depths (all p>0.05). Titanium implants with peri-implantitis have the capacity to reosseointegrate following regenerative surgery. However, treatment response is contingent upon the chemotherapeutic agent selection. Additional chemical treatment with 1.5% NaOCl lead to the most favorable results in terms of changes in defect depth and percentage of reosseointegration as compared to CHX, which may hinder reosseointegration.

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.

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.

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

PurposeTo 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 methodsA 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.ResultsThirty-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.ConclusionExpectable 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.

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.

Assessment of soft and hard tissue dimensions following different treatment approaches of ligature‐induced peri‐implantitis defects

To evaluate peri-implant tissue dimensions following nonsurgical (NS) and surgical therapy (S) employing different decontamination protocols of advanced ligature-induced peri-implantitis in dogs. Peri-implantitis defects (n=5 dogs, n=30 implants) were randomly and equally allocated in a split-mouth design to NS or S treatment using either an Er:YAG laser (ERL), an ultrasonic device (VUS), or plastic curettes+local application of metronidazole gel (PCM), respectively. Horizontal bone thickness (hBT) and soft tissue thickness (hMT) were measured at different reference points: (v0) at the marginal portion of the peri-implant mucosa (PM); (v1) at 50% of the distance from PM to bone crest (BC); (v2) at the BC; (v3) at the most coronal extension of the bone-to-implant contact. Vertical peri-implant tissue height was calculated from PM to BC. All of the treatment groups showed a gradual hMT increase from v0 to the v2 reference point, followed by a reduction from v2 to the v3 region. The S-VUS subgroup tended to be associated with higher hMT values at the v0 region than the NS-VUS subgroup (0.44mm versus 0.31mm). PM-BC distance varied from 2.22 to 2.83mm in the NS group, and from 2.07 to 2.38 in the S group. Vertical and horizontal peri-implant tissue dimensions were similar in different treatment groups.

Assessment of peri-implant tissue dimensions following surgical therapy of advanced ligature-induced peri-implantitis defects

BackgroundTo evaluate peri-implant tissue dimensions following implantoplasty and/or regenerative therapy of advanced ligature-induced peri-implantitis in dogs.Material and methodsAt all defect sites (n = 6 dogs, n = 48 implants), the intrabony component was filled with a particulate bovine-derived natural bone mineral (NBM). The supracrestal component was treated by either the application of an equine bone block (EB) or implantoplasty. In a split-mouth design, NBM and EB were soak-loaded with rhBMP-2 or sterile saline. All sites were covered using a native collagen membrane and left to heal in a submerged position for 12 weeks. The horizontal mucosal thickness (hMT) and bone thickness (hBT) were measured at four reference points: (v0) at the level of implant shoulder (IS), (v1) 50% of the distance IS-bone crest (BC), (v2) at the BC, and (v3) at the most coronal extension of the bone-to-implant contact.ResultsThe general tendency indicated a gradual increase in hMT from the IS (v0) toward BC (v2), which was more pronounced at implant sites treated with the regenerative approach. The hBT values increased from v2 to v3, with the highest values at the v3 region measured for implant sites treated with adjunctive rhBMP-2. For sites treated with implantoplasty, the linear regression model demonstrated an inverse correlation between hMT and hBT, whereas a positive correlation was observed at those sites treated with the regenerative approach.ConclusionHorizontal soft and hard tissue dimensions were similar among different treatment groups.

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.

Evaluation of air polishing with a sterile powder and mechanical debridement during regenerative surgical periimplantitis treatment: a study in dogs

ObjectivesTo evaluate the effectiveness of mechanical debridement and/or air polishing on the healing of ligature-induced buccal periimplantitis dehiscence defects in dogs.Material and methodsForty-eight implants were placed in the mandibles of twelve beagle dogs, and periimplantitis was induced for 2 months using ligatures. The resulting buccal dehiscence-type defects were surgically cleaned and augmented (xenogenic filler and resorbable membrane) according to one of the following treatments: (1) Cleaning with carbon curette (debridement - D) and guided bone regeneration (GBR/G): DG, (2) air polishing cleaning (A) and GBR: AG, (3) a combination of D/A/G: DAG, and (4) D/A without GBR: DA. After 2 months, histomorphometric and inflammatory evaluations were conducted.ResultsThe median bone gain after therapy ranged between 1.2 mm (DG) and 2.7 mm (AG). Relative bone gain was between 39% (DG) and 59% (AG). The lowest inflammation scores were obtained in DA without GBR (5.84), whereas significantly higher values between 8.2 and 9.4 were found in the groups with augmentation. At lingual sites without defects, scores ranged from 4.1 to 5.9. According to ISO, differences above 2.9 were considered representative for irritative properties.ConclusionsAll treatments resulted in partial regeneration of the defects. No treatment group showed a significantly (p < 0.05) better outcome. However, pretreatment with air polishing showed a tendency for less inflammation. Noteworthy, inflammation assessment showed an overall irritative potential after GBR in the evaluated early healing phase.Clinical relevancePeriimplantitis treatment still represents a big issue in daily practice and requires additional preclinical research in order to improve treatment concepts.

Microbial and host-derived biomarker changes during ligature-induced and spontaneous peri-implantitis in the Beagle dog.

To evaluate microbial and host-derived biomarker changes during experimental peri-implantitis in the Beagle dog. Limited data exist on the microbial and biomarker changes during progressive bone loss as result of experimental peri-implantitis. In total, 36 implants (ndogs =6) were assessed over 3 episodes of ligature-induced peri-implantitis followed by a period of spontaneous progression. Implants with hybrid (H) and completely rough (R) surface designs were used. Clinical and radiographic parameters were recorded at 4 timepoints. Peri-implant sulcus fluid was collected from the buccal and lingual aspects of the implants. The presence of 7 bacterial species and 2 host-derived biomarkers was assessed during the study period. Total bacterial counts were significantly correlated with marginal bone loss (MBL) (r=.21; P=.009). Further, Phorphyromonas gulae (Pg) and Tannerella forsythia (Tf) were commonly correlated with MBL, suppuration (SUP) and the sulcular bleeding index scores (mSBI) (P<.05). Other bacteria were further correlated with SUP, mSBI, and MBL. While the analyzed bacteria dropped, Prevotella intermedia (Pi) further increased during the spontaneous progressive phase (P<.05). Total bacterial load did not differ significantly between H and R implants. Host-derived IL-10 was undetected along the study period. IL-1β positively correlated with probing pocket depth (r=.18; P=.03). During spontaneous progression, H implants displayed statistically significant lower levels of IL-1β (P=.003). Experimental peri-implantitis is associated with an increase in bacterial counts. While Pg and Tf are associated with ligature-induced disease progression, Pi augmented its load during the spontaneous progressive phase. IL-1β is associated with pocket probing depth and influenced by implant surface characteristics during the spontaneous progression phase.

Ligature-induced periimplantitis surrounding thin sputtered HA-coated implants : An experimental study in dogs : Clinical and radiographic evaluations

Ligature-induced periimplantitis surrounding thin sputtered HA-coated implants : An experimental study in dogs : Clinical and radiographic evaluations

Reosseointegration after the surgical treatment of induced peri-implantitis: systematic review on current evidence and translation from the animal to the human model.

The aim of this study was to review the histologic evidence of reosseointegration and related influencing factors in experimental induced peri-implantitis. An electronic search was performed on Medline for animal studies that included a histometric evaluation of the amount of regenerated bone in contact with an implant surface. Questions raised in the study focused on the role of implant surfaces, bone regeneration and decontamination treatments in achieving reosseointegration. A detailed electronic search was then conducted on MEDLINE (PubMed) up to July 2017. One hundred and one articles were selected as abstract, thirty-seven articles assessed as full-text and sixteen finally included in the study. Reported measurements of reosseointegration varied significantly in the study, from 0 to 3.37 mm. There is histological evidence that reosseointegration can occur after treatment of ligature-induced peri-implantitis. However regenerated bone in contact with bone is generally restricted to the most apical portion of the peri-implant defect. Animal studies of induced peri-implantitis seem to indicate that rough surfaces can enhance reosseointegration as compared to smooth surfaces. With regard to bone regeneration techniques and materials, submerged healing and barrier membranes have shown a positive effect on reosseointegration. No evidence exists, however, about the specific role of different bone substitutes and their ability to improve bone formation. Growth factors have been shown to improve reosseointegration in animal models, though additional study is required to confirm the data. Several decontamination treatments have been shown to promote reosseointegration compared to control; however no specific procedure has proven superior to others in achieving reosseointegration.

TLR4 mediates alveolar bone resorption in experimental peri-implantitis through regulation of CD45+ cell infiltration, RANKL/OPG ratio, and inflammatory cytokine production.

The present study was to determine the role of Toll-like receptor 4 (TLR4) signaling in inflammation and alveolar bone resorption using a murine model ofPorphyromonas gingivalis-associated ligature-induced peri-implantitis. Smooth surface titanium implants were placed in the left maxilla alveolar bone 6weeks after extraction of first and second molars in Wild-type (WT) and TLR4-/- (TLR4 KO) mice. Silk ligatures immersed withP. gingivaliswere tied around the implants 4weeks after the implant placement and confirmation of osteointegration. Two weeks after the ligation, bone resorption, osteoclastogenesis, cellular inflammatory responses, and gingival mRNA expression levels of cytokines were assessed by micro-computed tomography, tartrate-resistant acid phosphatase (TRAP) staining, immunobiological examination and Real-time quantitative polymerase chain reaction, respectively. In both WT and TLR4 KO mice, the bone resorption around implants was significantly increased in the P. gingivalis/ligation group compared with control group. In P. gingivalis/ligation group, the levels of bone resorption, TRAP+ cell formation, and gingival CD3+ and CD45+ cell infiltration were significantly decreased in TLR4 KO mice compared with that in WT mice. Receptor activator of nuclear factor-kappa B ligand /osteoprotegerin (RANKL/OPG) ratio was significantly increased after P. gingivalis/ligation treatment in WT mice not in TLR4 KO mice. When comparing the P. gingivalis/ligation group with the respective control group, gingival mRNA expressions of IL-1β, IFN-γ, and 1L-17 were significantly increased in TLR4 KO mice. This study suggests that TLR4 mediates alveolar bone resorption in P. gingivalis associated ligature-induced peri-implantitis through regulation of immune B cell infiltration, RANKL/OPG expression ratio, and differential inflammatory cytokine production.

Diagnostic accuracy of the implant stability quotient in monitoring progressive peri-implant bone loss: An experimental study in dogs.

To investigate the impact of progressive bone loss in an experimental peri-implantitis model in the dog upon the implant stability quotient (ISQ) measured in the course of induced and spontaneous conditions of disease, and to evaluate the association between the clinical parameters and ISQ. Seventy-two implants were placed in 12 Beagle dogs. Of these, 36 implants in six dogs were assessed during ligature-induced peri-implantitis (three timepoints) and at one timepoint following a period of spontaneous progression. The ISQ was recorded using resonance frequency analysis (RFA). Furthermore, the clinical peri-implant parameters were registered at four sites per implant at each timepoint. Marginal bone loss (MBL) was determined using computed tomography at four sites per implant and bone-to-implant contact (BIC) was assessed from histological samples. A linear regression model was estimated by generalized estimation equations (GEEs) in order to study the MBL-ISQ values at each measurement timepoint. Pearson's correlation test was applied. None of the implants failed during the study period. At implant level, a strong negative correlation was found for all timepoints between ISQ and MBL (r=-0.58; p<0.001). Accordingly, as follow-up progressed, lower ISQ and higher MBL values were observed. A prediction of MBL depending on the ISQ values and timepoints showed a decrease in one ISQ unit to be related to ~1mm of MBL. Likewise, a statistically significant correlation was found between BIC and ISQ evaluated after spontaneous chronification of peri-implantitis (r=0.34; p=0.04). Nevertheless, the ISQ values failed to correlate to any of the clinical parameters recorded. Resonance frequency analysis seems accurate in diagnosing progressive bone loss, as a statistically significant decrease in ISQ was recorded in the course of peri-implant disease. Nevertheless, the clinical relevance of this observation as a diagnostic tool is debatable, since implant stability remains high.

Estimation of the diagnostic accuracy of clinical parameters for monitoring peri-implantitis progression: An experimental canine study.

Lack of consensus on the clinical parameters of peri-implantitis may complicate accurate diagnosis of the disorder. Furthermore, the lack of reliable estimates of the diagnostic capacity of the clinical endpoints precludes the definition of an effective treatment protocol for peri-implantitis. The present canine study assesses the diagnostic accuracy of the clinical parameters for monitoring the peri-implant tissues in a controlled ligature-induced peri-implantitis model followed by a spontaneous progression phase. Six beagle dogs were followed-up on during three episodes of ligature-induced peri-implantitis and a further episode of spontaneous progression. Probing depth (PD), bleeding on probing (BOP), mucosal recession (MR), and suppuration (SUP) were recorded at four sites per implant and at four study timepoints. Moreover, the implant mucosal index (IMI) was calculated at implant level. Marginal bone loss (MBL) was determined using computed tomography at four sites per implant. A linear regression model was used to estimate clinical and radiological parameters during peri-implantitis progression. Progressive peri-implant bone loss is characterized by an increase in PD, more profuse BOP, MR, and SUP in advanced cases (p<0.001). However, even in the presence of severe bone loss, SUP was not a common finding, with an incidence of approximately 10% at the last timepoint. These clinical parameters were significantly correlated to MBL at most of the timepoints. The IMI, in turn, showed a positive correlation to MBL and the peri-implant inflammatory signs (r=0.39; p<0.001), with a tendency to exhibit higher scores during ligature-induced peri-implantitis, followed by a slight decrease during the spontaneous progression period. The clinical features of peri-implantitis and spontaneous progression of the disorder may facilitate an accurate monitoring of peri-implant pathologic bone loss.

Microbiologic effect of two topical anti-infective treatments on ligature-induced peri-implantitis: A pilot study in dogs.

The aim of this split-mouth design pilot study in dogs was to assess microbiologic effects of two topical anti-infective treatment protocols on dental implants subjected to ligature-induced peri-implantitis, without use of systemic antibiotics. Eight adult Beagle dogs each received four dental implants in contralateral, edentulated, mandibular jaw quadrants. After 8 weeks, silk ligatures were installed, to be removed after another 8 weeks. After 6 additional weeks, induced peri-implantitis lesions were subjected to either antimicrobial photodynamic therapy (aPDT) or a topical tetracycline (TTC) hydrochloride (50 mg/mL) solution. Microbiologic samples were collected from the deepest proximal peri-implantitis site in each jaw quadrant before and after treatment. The samples were analyzed using DNA-DNA hybridization checkerboard technique. Peri-implantitis induction successfully produced lesions with microbiologic characteristics similar to those found in humans. Overall results showed effective bacterial count reductions for both protocols. aPDT demonstrated major reductions of the red complex, but no statistical differences between groups were observed when adjusted for multiple comparisons. aPDT and TTC successfully decontaminated infected implant surfaces. Implant decontamination with aPDT appears to be a viable alternative to TTC in the management of peri-implantitis infection.

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Background/Aims: The roles of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in peri-implantitis are unclear. Here, we used a canine model of peri-implantitis to explore the effects of inhibiting NF-κB with pyrrolidine dithiocarbamate (PDTC) on the inflammatory response in ligature-induced peri-implantitis. Methods: After successfully establishing the peri-implantitis model, beagles were randomly assigned to normal, model or PDTC groups. ELISA tests were used to determine the levels of interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). Immunohistochemistry was employed to assess the expression of NF-κB p65. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA levels of TLR4 and NF-κB p65, and western blot analysis was used to measure the protein levels of TLR4 in periodontal tissues from each group. Periodontal ligament fibroblasts (PDLFs) were cultured and subsequently classified into PDLF normal, PDLF model, PDLF LPS, PDLF PDTC, and PDLF LPS + PDTC groups. An immunofluorescence assay was used to measure the expression level of NF-κB p65. The CCK-8 assay and flow cytometry were performed to evaluate cell proliferation and apoptosis. Results: The in vitro results indicated that NF-κB p65 and TLR4 were upregulated in canine periodontal tissues, and PDTC could suppress the expression levels of NF-κB p65 and TLR4. Inflammation could increase TLR4 protein expression in canine periodontal tissue, and PDTC could inhibit the inflammation-induced increase in TLR4 protein expression. These results revealed that PDTC could reverse the LPS-induced increases in the levels of IL-1, IL-6, IL-8 and TNF-α. In vivo, the results demonstrated that PDTC inhibited the LPS-induced NF-κB p65 upregulation, and PDTC could reverse the inhibitory effect of the PDLF model + LPS on the proliferation of periodontal fibroblasts. The results also showed that in the PDLF model, LPS promoted PDLF apoptosis by inducing implant periodontitis in canines, but PDTC inhibited the PDLF apoptosis and relieved implant periodontitis in canines. Conclusion: Based on our results, we concluded that PDTC can inhibit the expression of NF-κB and alleviate the inflammatory response induced by LPS, thereby preventing periodontal inflammation and reducing the development of peri-implantitis.

Influence of Microtextured Implant Surfaces on Peri-implantitis and Its Treatment: A Preclinical Trial.

The prevalence of peri-implantitis has increased significantly, forcing clinicians to search for ways to prevent it. Laser-microtextured surfaces promote soft tissue attachment and provide a tight seal around implants. Hence, the aim of this study was to examine the clinical, radiographic, and histologic features of ligature-induced peri-implantitis, as well as the effect of surgical treatment of these induced peri-implantitis lesions on laser-microtextured implants in a controlled animal model. Six mini-pigs (three males/three females) received 6 implants each (3 resorbable blast textured [RBT] implants and 3 laser-microtextured [LM] implants) in mandibular premolar sites, for a total of 36 implants. Two groups were identified based on the time point of sample analysis. After osseointegration was achieved, metal wire ligatures were placed and left for 12 weeks. Group 1 samples were then obtained, and group 2 samples received rescue therapy following a guided bone regeneration (GBR) protocol. Sample collection in group 2 was completed 12 weeks after the samples were submerged and treated. All samples were analyzed histologically and measurements were taken. Four implants (three RBT, one LM) were lost at early time points because of implant instability. Interimplant distances and soft tissue thicknesses varied subtly between groups. More notable was the mean (± standard error of the mean) crestal bone loss (group 1: 1.860 ± 1.618 mm [LM] and 2.440 ± 2.691 mm [RBT]; group 2: 2.04 ± 1.613 mm [LM] and 3.00 ± 2.196 mm [RBT]) (P < .05), as demonstrated by a paired t test. Histologic pocket depth was also greater at RBT sites than at LM sites (4.448 ± 2.839 mm and 4.121 ± 2.251 mm, respectively, in group 1; and 3.537 ± 2.719 mm and 2.339 ± 1.852 mm, respectively [P < .005] in group 2). LM implants had less crestal bone loss and shallower histologic pocket depth compared with their RBT counterparts. Also, LM implants had higher bone fill when a rescue therapy (GBR) was performed.

Bone tissue engineering in oral peri-implant defects in preclinical in vivo research: A systematic review and meta-analysis.

The regeneration and establishment of osseointegration within oral peri-implant bone defects remains a clinical challenge. Bone tissue engineering (BTE) is emerging as a promising alternative to autogenous and/or biomaterial-based bone grafting. The objective of this systematic review was to answer the focused question: in animal models, do cell-based BTE strategies enhance bone regeneration and/or implant osseointegration in experimental peri-implant defects, compared with grafting with autogenous bone or only biomaterial scaffolds? Electronic databases were searched for controlled animal studies reporting on peri-implant defects and implantation of mesenchymal stem cells (MSC) or other cells seeded on biomaterial scaffolds, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Random effects meta-analyses were performed for the outcomes histomorphometric bone area fraction (BA) and bone-to-implant contact (BIC). Nineteen studies reporting on large animal models (dogs and sheep) were included. Experimental defects were created surgically (16 studies) or via ligature-induced peri-implantitis (LIPI, three studies). In general, studies presented with an unclear to high risk of bias. In most studies, MSC were used in combination with alloplastic mineral phase or polymer scaffolds; no study directly compared cell-loaded scaffolds vs. autogenous bone. In three studies, cells were also modified by ex vivo gene transfer of osteoinductive factors. The meta-analyses indicated statistically significant benefits in favour of: (a) cell-loaded vs. cell-free scaffolds [weighted mean differences (WMD) of 10.73-12.30% BA and 11.77-15.15% BIC] in canine surgical defect and LIPI models; and (b) gene-modified vs. unmodified cells (WMD of 29.44% BA and 16.50% BIC) in canine LIPI models. Overall, heterogeneity in the meta-analyses was high (I2 70-88%); considerable variation was observed among studies regarding the nature of cells and scaffolds used. In summary, bone regeneration and osseointegration in peri-implant defects are enhanced by the addition of osteogenic cells to biomaterial scaffolds. Although the direction of treatment outcome is clearly in favour of BTE strategies, due to the limited magnitude of treatment effect observed, no conclusive statements regarding the clinical benefit of such procedures for oral indications can yet be made. Copyright © 2017 John Wiley & Sons, Ltd.