The role of autophagy in odontogenesis, dental implant surgery, periapical and periodontal diseases.

Autophagy is a cellular process that is evolutionarily conserved, involving the sequestration of damaged organelles and proteins into autophagic vesicles, which subsequently fuse with lysosomes for degradation. Autophagy controls the development of many diseases by influencing apoptosis, inflammation, the immune response and different cellular processes. Autophagy plays a significant role in the aetiology of disorders associated with dentistry. Autophagy controls odontogenesis. Furthermore, it is implicated in the pathophysiology of pulpitis and periapical disorders. It enhances the survival, penetration and colonization of periodontal pathogenic bacteria into the host periodontal tissues and facilitates their escape from host defences. Autophagy plays a crucial role in mitigating exaggerated inflammatory reactions within the host's system during instances of infection and inflammation. Autophagy also plays a role in the relationship between periodontal disease and systemic diseases. Autophagy promotes wound healing and may enhance implant osseointegration. This study reviews autophagy's dento-alveolar effects, focusing on its role in odontogenesis, periapical diseases, periodontal diseases and dental implant surgery, providing valuable insights for dentists on tooth development and dental applications. A thorough examination of autophagy has the potential to discover novel and efficacious treatment targets within the field of dentistry.

New insights on collagen structural organization and spatial distribution around dental implants: a comparison between machined and laser-treated surfaces.

BACKGROUND: One of the main factors for the osseointegration of dental implants is the development of an adequate soft tissue barrier, mainly composed by collagen, which protects the implant from bacterial development. The structural features of the peri-implant collagen are influenced by the implant components and, in particular, by the type of the surface. In the clinical practice, healing abutments are characterized by smooth surfaces, named machined. Recently, a new laser technique, Synthegra, has been developed to obtain a topography-controlled surface with micrometric regular pores that seems reducing the risk of peri-implantitis. Based on this background, this study aims investigating the structural organization and spatial distribution of collagen surrounding healing abutments characterized by laser-treated and machined surfaces. METHODS: Gingiva portions surrounding custom-made healing abutments (HA), characterized by alternated laser-treated and machined surfaces, were collected and analyzed by combining Fourier Transform InfraRed Imaging (FTIRI) spectroscopy, a non-invasive and high-resolution bidimensional analytical technique, with histological and multivariate analyses. RESULTS: Masson's trichrome staining, specific for collagen, highlighted a massive presence of collagen in all the analyzed samples, evidencing a surface-related spatial distribution. The nature of collagen, investigated by the FTIRI spectroscopy, appeared more abundant close to the laser-treated surface, with a perpendicular disposition of the bundles respect to the HA; conversely, a parallel distribution was observed around the machined surface. A different secondary structure was also found, with a higher amount of triple helices and a lower quantity of random coils in collagen close to the laser treated surfaces. CONCLUSIONS: FTIRI spectroscopy demonstrates that the use of a laser treated transmucosal surface can improve the morphological organization of the peri-implant collagen, which presents a distribution more similar to that of natural teeth. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov Identifier: (Registration Number: NCT05754970). Registered 06/03/2023, retrospectively registered, https://clinicaltrials.gov/show/NCT05754970 .

Contact allergies to dental materials in patients.

BACKGROUND: Concerns regarding contact allergies and intolerance reactions to dental materials are widespread among patients. Development of novel dental materials and less frequent amalgam use may alter sensitization profiles in patients with possible contact allergy. OBJECTIVES: To analyse current sensitization patterns to dental materials in patients with suspected contact allergy. METHODS: This retrospective, multicentre analysis from the Information Network of Departments of Dermatology (IVDK) selected participants from 169 834 people tested in 2005-2019 and registered with (i) an affected area of 'mouth' (and 'lips'/'perioral'), (ii) with the dental material in question belonging to one of three groups (dental filling materials, oral implants or dentures or equivalents) and (iii) with patch-testing done in parallel with the German baseline series, (dental) metal series and dental technician series. RESULTS: A total of 2730 of 169 834 tested patients met the inclusion criteria. The patients were predominantly women (81.2%) aged ≥ 40 years (92.8%). The sensitization rates with confirmed allergic contact stomatitis in women (n = 444) were highest for metals (nickel 28.6%, palladium 21.4%, amalgam 10.9%), (meth)acrylates [2-hydroxyethyl methacrylate (HEMA) 4.8%] and the substances propolis (6.8%) and 'balsam of Peru' (11.4%). The most relevant acrylates were HEMA, 2-hydroxypropyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate and pentaerythritol triacrylate. Few men were diagnosed with allergic contact stomatitis (n = 68); sensitization rates in men were highest for propolis (14.9%) and amalgam (13.6%). CONCLUSIONS: Allergic contact stomatitis to dental materials is rare. Patch testing should not only focus on metals such as nickel, palladium, amalgam and gold, but also (meth)acrylates and the natural substances propolis and 'balsam of Peru'.

Efficacy of ozonated olive oil against peri-implant microbes isolated from peri-implantitis.

This study aimed to investigate the antibacterial and antimicrobial activity of ozone gel against oral biofilms grown on titanium dental implant discs. The experiment used medical grade five titanium discs on which peri-implant isolated biofilms were grown. The experimental groups were control, Streptococcus mutans (S. mutans) and Granulicatella adiacens (G. adiacens), (n = 6). The oral microbes grown on titanium discs were exposed to ozone gel for 3 minutes and the antibacterial activity was assessed by turbidity test and adherence test for the antibiofilm activity test. Bacterial morphology and confluence were investigated by scanning electron microscopy (SEM), (n=3). Two bacterial species were identified from the peri-implant sample, S. mutans and G. adiacens. The results showed that adding ozone to the bacterial biofilm on titanium dental implants did not exhibit significant antibacterial activity against S. mutans. Moreover, there was no significant difference in antibiofilm activity between control and treatment groups. However, significant antibacterial and antibiofilm effect was exhibited by ozone gel against G. adiacens. Ozonated olive oil can be considered as a potential antimicrobial agent for disinfecting dental implant surfaces and treating peri-implantitis.

Effects of immediate loading directionality on the mechanical sensing protein PIEZO1 expression and early-stage healing process of peri-implant bone.

BACKGROUND: The reduced treatment time of dental implants with immediate loading protocol is an appealing solution for dentists and patients. However, there remains a significant risk of early peri-implant bone response following the placement of immediately loaded implants, and limited information is available regarding loading directions and the associated in vivo characteristics of peri-implant bone during the early stages. This study aimed to investigate the effects of immediate loading directionality on the expression of mechanical sensing protein PIEZO1 and the healing process of peri-implant bone in the early stage. METHODS: Thirty-two implants were inserted into the goat iliac crest models with 10 N static lateral immediate loading applied, followed by histological, histomorphological, immunohistochemical, X-ray microscopy and energy dispersive X-ray spectroscopy evaluations conducted after 10 days. RESULTS: From evaluations at the cellular, tissue, and organ levels, it was observed that the expression of mechanical sensing protein PIEZO1 in peri-implant bone was significantly higher in the compressive side compared to the tensile side. This finding coincided with trends observed in interfacial bone extracellular matrix (ECM) contact percentage, bone mass, and new bone formation. CONCLUSIONS: This study provides a novel insight into the immediate loading directionality as a potential influence factor for dental implant treatments by demonstrating differential effects on the mechanical sensing protein PIEZO1 expression and related early-stage healing processes of peri-implant bone. Immediate loading directions serve as potential therapeutic influence factors for peri-implant bone during its early healing stage.

Clinical, immunological and microbiological evaluation of experimental peri-implant mucositis and gingivitis in subjects with Grade C, stage III/IV periodontitis background.

AIM: To compare individuals with a periodontitis background (Grade C, stage III/IV-formerly generalized aggressive periodontitis) (H-GAP) with periodontally healthy subjects (H-Health) in terms of molecular changes (immunological/microbiological) accompanying experimental peri-implant mucositis and gingivitis. MATERIALS AND METHODS: H-GAP and control (H-Health) subjects were recruited, and experimental mucositis/gingivitis was induced around a single screw-retained implant and one contralateral tooth. Participants refrained from oral hygiene for 21 days in the selected areas, followed by professional prophylaxis and hygiene instructions for 21 days. Clinical parameters, immunological markers (multiplex analysis) and microbial data (16S rRNA gene sequencing) were collected at baseline, during induction (7, 14 and 21 days) and following remission (42 days). RESULTS: Clinically, no significant differences were observed between the groups (n = 10/each group) (H-GAP vs. H-Health) (p > .05, Mann-Whitney test) and the type of site (tooth vs. implant) (p > .05, Wilcoxon test) at the time of onset and resolution, or severity of gingival/mucosal inflammation. H-GAP displayed lower concentrations of the cytokines interleukin (IL)-1B, IL-4, IL-17, tumor necrosis factor-α and interferon-γ around implants than H-Health at baseline and during induction of mucositis (p < .05, Mann-Whitney test). In both groups, implants showed significantly higher inflammatory background at baseline and all subsequent visits when compared with teeth (p < .05, Wilcoxon test). Alpha and ß-diversity metrics showed a significant shift in the microbiome composition and abundances of core species during induction and resolution of peri-implant mucositis and gingivitis (p < .05, restricted maximum likelihood method of Shannon and Bray-Curtis indices, respectively). Differences were not significant for these parameters between the H-Health and H-GAP groups when the periodontal and peri-implant microbiomes were compared separately; however, at each time point, the peri-implant microbiome differed significantly from the periodontal microbiome. CONCLUSIONS: Within the limitations of this pilot study (e.g. low power), it can be concluded that different microbial shifts contribute to the onset and progression of inflammatory responses around teeth and implants and that history of periodontal disease experience plays an additional role in modulating the immune response of peri-implant and periodontal tissues to biofilm accumulation.

Is transmucosal healing of an implant as effective as submerged healing when simultaneous guided bone regeneration is performed? A preclinical study.

AIM: To investigate whether transmucosal healing is as effective as submerged healing in terms of buccal bone regeneration when guided bone regeneration (GBR) is performed simultaneously with implant placement. MATERIALS AND METHODS: In six dogs, buccal dehiscence defects were created in the edentulous mandibular ridge, sized 5 × 5 × 3 mm (length × height × depth). In each defect, a bone-level implant was placed, and four experimental groups were randomly assigned as follows: (i) transmucosal healing with GBR (T-GBR), (ii) transmucosal healing without GBR (T-control), (iii) submerged healing with GBR (S-GBR) and (iv) submerged healing without GBR (S-control). Data analyses were based on histological slides 5 months after implant placement. RESULTS: The T-GBR group showed significant differences compared to the control groups regarding defect height resolution, buccal bone thickness and mineralized tissue area (p < .05), but showed no significant differences when compared with the S-GBR group (p > .05). CONCLUSIONS: The mode of healing (transmucosal vs. submerged) does not influence bone regeneration at implant sites. The clinician may therefore choose the approach based on further clinical and patient-specific parameters.

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.

Short (≤6 mm) compared with ≥10-mm dental implants in different clinical scenarios: A systematic review of randomized clinical trials with meta-analysis, trial sequential analysis and quality of evidence grading.

AIM: To systematically identify, synthesize and critically summarize the available scientific evidence from randomized controlled trials (RCTs) regarding whether short (≤6 mm) perform as well as long (≥10 mm) implants regarding implant survival, marginal bone loss, and biologic and prosthetic complications in different clinical scenarios. MATERIALS AND METHODS: Cochrane Collaboration's risk of bias tool and the GRADE approach were applied. Results were synthesized using random-effects meta-analyses assessed by trial sequential analyses. RESULTS: Forty reports on 19 RCTs comprising 2214 (1097 short; 1117 long) implants were included. Moderate/high certainty/quality evidence demonstrated similar 5-year survival rates for ≤6-mm and ≥10-mm implants in non-augmented bone and full-mouth rehabilitation in either jaw, and for 6-mm implants in the maxilla instead of sinus lift. Nevertheless, the evidence for 5-year survival rates remains inconclusive or insufficient for the remaining combinations of implant lengths and clinical scenarios. They include 4-mm and 5-mm implants as alternatives to sinus lift as well as placing all implant lengths ≤6 mm instead of vertical ridge augmentation with long implants. Marginal bone level and short- and long-term biologic or prosthetic complications were similar. CONCLUSIONS: Based on moderate/high certainty/quality evidence from 5-year RCTs, implants ≤6 mm may be viable alternatives to ≥10-mm implants in either jaw in native bone and full-arch rehabilitation, and 6-mm implants may be used as an alternative to sinus lift. TRIAL REGISTRATION: PROSPERO ID: CRD42021254365.

Augmentation of keratinized tissue using autogenous soft-tissue grafts and collagen-based soft-tissue substitutes at teeth and dental implants: Histological findings in a pilot pre-clinical study.

AIM: To histomorphometrically assess three treatment modalities for gaining keratinized tissue (KT) at teeth and at dental implants. MATERIALS AND METHODS: In five dogs, the distal roots of the mandibular second, third and fourth premolars were extracted. Dental implants were placed at the distal root areas 2 months later. After another 2 months, KT augmentation was performed at both distal (implants) and at mesial root (teeth) areas in the presence (wKT groups) or absence (w/oKT groups) of a KT band at the mucosal/gingival level. Three treatment modalities were applied randomly: apically positioned flap only (APF), free gingival grafts (FGGs) and xenogeneic collagen matrices (XCMs). A combination of the above produced six groups. Two months later, tissue sections were harvested and analysed histomorphometrically. RESULTS: The median KT height and length were greatest at implants with FGG in both wKT (3.7 and 5.1 mm, respectively) and w/oKT groups (3.7 and 4.6 mm), and at teeth with FGG in wKT groups (3.7 and 6.1 mm) and with APF in the w/oKT groups (3.9 and 4.4 mm). The XCM and APF produced more favourable results at teeth than at implants. CONCLUSIONS: FGG was advantageous in gaining KT, especially at implants.

Randomized controlled multi-centre study comparing shorter dental implants (6 mm) to longer dental implants (11-15 mm) in combination with sinus floor elevation procedures: 10-year data.

AIM: To compare implant survival and complication rates between shorter and standard-length implants with sinus augmentation and restored with single crowns, at 10 years of loading. MATERIALS AND METHODS: One-hundred and one patients (137 implants) with a ridge height of 5-7 mm in the posterior maxilla were randomly assigned to two treatment modalities: shorter implants (6 mm) (group short [GS]) or standard-length implants (11-15 mm) with sinus grafting (group graft [GG]). Following the insertion of final restorations, patients were regularly recalled for up to 10 years. Assessed outcomes encompassed implant survival, marginal bone levels (MBLs), biological and technical parameters and patient-reported outcome measures (OHIP-49 = Oral Health Impact Profile). Non-parametric statistical analysis was used to analyse the data. RESULTS: For the 5- to 10-year follow-up period, 77 patients with 105 implants (GS: 36 patients/48 implants; GG: 41/57) were available for re-examination (drop-out rate 21%). Implant survival rates at the patient level were 96.0% (GS; 2 failures) and 100% (GG) (inter-group p = .24). Median MBLs amounted to 0.00 mm (min 0.00; max 3.25; GS) and 0.00 mm (min 0.00; max 4.55; GG) (inter-group p = .73). Technical complications predominantly occurred within the first 5 years (inter-group p > .05). Peri-implantitis rates were 4.2% (GS) and 13.3% (GG) (intergroup p = .37). Median OHIP-49 scores were 7.00 (0.00; 39.00; GS) and 9.00 (0.00; 196; GG) (inter-group p = .61) at 10 years. CONCLUSIONS: Based on similar 10-year implant survival rates, reduced patient morbidity and lower costs, the use of shorter dental implants might well serve as an alternative treatment concept to longer implants placed in conjunction with sinus grafting for patients with a limited ridge height in the posterior maxilla. Study register: https://clinicaltrials.gov/ct2/show/NCT01030523.

Improved positional accuracy of dental implant placement using a haptic and machine-vision-controlled collaborative surgery robot: A pilot randomized controlled trial.

AIM: To compare the implant accuracy, safety and morbidity between robot-assisted and freehand dental implant placement. MATERIALS AND METHODS: Subjects requiring single-site dental implant placement were recruited. Patients were randomly allocated to freehand implant placement and robot-assisted implant placement. Differences in positional accuracy of the implant, surgical morbidity and complications were assessed. The significance of intergroup differences was tested with an intention-to-treat analysis and a per-protocol (PP) analysis (excluding one patient due to calibration error). RESULTS: Twenty patients (with a median age of 37, 13 female) were included. One subject assigned to the robotic arm was excluded from the PP analysis because of a large calibration error due to the dislodgement of the index. For robot-assisted and freehand implant placement, with the PP analysis, the median (25th-75th percentile) platform global deviation, apex global deviation and angular deviation were 1.23 (0.9-1.4) mm/1.9 (1.2-2.3) mm (p = .03, the Mann-Whitney U-test), 1.40 (1.1-1.6) mm/2.1 (1.7-3.9) mm (p < .01) and 3.0 (0.9-6.0)°/6.7 (2.2-13.9)° (p = .08), respectively. Both methods showed limited damage to the alveolar ridge and had similar peri- and post-operative morbidity and safety. CONCLUSIONS: Robot-assisted implant placement enabled greater positional accuracy of the implant compared to freehand placement in this pilot trial. The robotic system should be further developed to simplify surgical procedures and improve accuracy and be validated in properly sized trials assessing the full spectrum of relevant outcomes.

Patient-reported outcomes following dental implant rehabilitation according to reason for missing teeth: A survey from a Norwegian population 8 years following treatment.

AIM: The aim of this study was to assess patient-reported outcomes (PROs) 8 years after dental implant rehabilitation in a sample with tooth loss due to periodontitis (TLP) and a sample with missing teeth for other reasons (MTOR). MATERIALS AND METHODS: The Norwegian National Insurance Scheme registry of subsidized dental implant therapy was searched, and patients (n = 3083) rehabilitated with dental implants in 2014 were mailed a questionnaire. PROs were described by relative frequencies, and the TLP and MTOR subsamples were compared using chi-square test. Multiple linear regression analyses were used to investigate variables potentially predicting PROs. RESULTS: Of the respondents (n = 1299), more than 90% were partly or fully satisfied with the treatment outcome. Complications were reported by 44.2%. Patients who lost teeth due to periodontitis (n = 784) reported greater oral function improvement and better pre-treatment information, and were more likely to experience complications when compared with patients who lost teeth for other reasons (n = 515). Age, level of education, self-funded cost, pre-treatment information, history of complications and the reason for missing teeth were found to predict PROs. CONCLUSIONS: In a Norwegian population rehabilitated with dental implants in 2014, satisfaction with the treatment outcome and the aesthetic outcome was high, irrespective of the reason for missing teeth. Self-report of complications and lack of pre-treatment information were the strongest predictors of inferior patient satisfaction and also predicted inferior oral function.

Clinical outcomes following atrophic alveolar ridge reconstruction using collagenated xenogeneic bone block or autogenous bone block: One-year follow-up of a randomized controlled clinical.

AIM: This investigation aimed to evaluate the 1-year survival of implants placed after staged lateral alveolar ridge augmentation using equine-derived collagenated xenogeneic bone blocks (CXBBs) or autogenous bone block (ABB). MATERIALS AND METHODS: Fifty patients who underwent lateral augmentation in a previous trial were included. The primary outcome measure was implant survival at the 1-year follow-up, and secondary outcomes included implant success, peri-implant clinical and volumetric parameters, pink aesthetic scores (PES) and patient-reported outcome measures. Data analysis involved Fisher's exact test, the Mann-Whitney U-test and the Wilcoxon signed-rank test. RESULTS: In this study, no late implant failures were observed. The cumulative survival rates were 78.6% for the CXBB group and 90.9% for the ABB group, with no difference between the groups. Similarly, the success rates were 53.6% and 63.6%, respectively, showing no significant difference. Peri-implant clinical and volumetric parameters indicated the presence of healthy peri-implant tissues surrounding implants placed in both CXBB- and ABB-augmented sites. PES were 8.5 and 11.0 for implants placed in CXBB- and ABB-augmented sites, respectively. Furthermore, patient satisfaction rates were high and similar between the groups. CONCLUSIONS: Dental implants placed in both CXBB- and ABB-augmented ridges demonstrated no statistically significant differences in clinical, volumetric and aesthetic outcomes, along with high patient satisfaction rates.

Clinical outcomes and risk factor analysis of dental implants inserted with lateral maxillary sinus floor augmentation: A 3- to 8-year retrospective study.

AIM: To evaluate the 3- to 8-year outcomes of dental implants placed with lateral sinus floor augmentation (LSFA) and to identify factors affecting implant survival. MATERIALS AND METHODS: This retrospective study was performed by screening all implants placed with LSFA procedures, which were conducted between January 2012 and December 2016. Subantral bone gain (SABG) and apical bone height (ABH) were assessed using panoramic radiographs. The cumulative survival rate of implants was analysed using life-table analysis and Kaplan-Meier survival curves. The influential risk factors affecting survival were assessed using univariate log-rank tests and multivariable mixture cure rate model. Implant complications were recorded. RESULTS: Based on the established criteria, a total of 449 patients (760 implants) were included in this study. In the 3- to 8-year follow-up (mean ± SD, 5.81 ± 1.33 years), 15 implants in 14 patients failed, with a CRS of 96.81% on an implant basis and 95.07% on a patient basis. A history of periodontitis and poor compliance with supportive periodontal treatment was associated with a significantly higher risk of implant failure at both implant and patient levels. Significant decreases in ABH occurred during each yearly interval except for 3 years. A similar trend has been observed for SABG at 1, 2, 6 and 8 years. The total complication rate was 31.84% on implant basis, with peri-implant mucositis (21.58%) being the most frequent biologic complication and porcelain cracking (5.00%) being the most common technical complication. CONCLUSIONS: Implant with LSFA is a reliable treatment option in atrophic maxilla. A history of periodontitis without regular supportive periodontal treatment was identified as a predictor for implant failure. Slight but significant shrinkage of vertically augmented bone can be observed after implant placement.

Flapless early implant placement into the uncalcified provisional matrix-Does it lead to osseointegration of the implant? A preclinical study.

AIM: To test whether early implant placement into the extraction socket containing an uncalcified provisional matrix leads to successful osseointegration and stable marginal bone levels. MATERIALS AND METHODS: In six mongrel dogs, the mandibular molars were extracted. Three weeks later, early implant placement was performed according to three experimental protocols: (i) flapless implant placement with preservation of the provisional matrix; (ii) flap elevation, socket debridement and implant placement; and (iii) flap elevation, socket debridement, implant placement and guided bone regeneration (GBR). One untreated extraction socket served as a control group. Data analyses were based on histologic slides 3 months after implant placement. RESULTS: There were no differences in bone-to-implant contact between the three experimental groups (66.97%, 58.89% and 60.89%, respectively) (inter-group comparison p = .42). Marginal bone levels, first bone-to-implant contact as well as the thickness of the connective tissue did not reveal any significant differences between the groups (p = .85, .60 and .65, respectively). CONCLUSIONS: Flapless early implant placement into posterior extraction sockets was as effective as an open flap approach in conjunction with GBR. Mineralization of the socket seems to occur irrespective of the presence of dental implants or biomaterials.

CCR2 is a potential therapeutic target in peri-implantitis.

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: CCR2 may be a potential target for peri-implantitis treatment by harnessing the immune-inflammatory response to modulate the local inflammation and osteoclast activity.

Dynamic analyses of a soft tissue-implant interface: Biological responses to immediate versus delayed dental implants.

AIM: To qualitatively and quantitatively evaluate the formation and maturation of peri-implant soft tissues around 'immediate' and 'delayed' implants. MATERIALS AND METHODS: Miniaturized titanium implants were placed in either maxillary first molar (mxM1) fresh extraction sockets or healed mxM1 sites in mice. Peri-implant soft tissues were evaluated at multiple timepoints to assess the molecular mechanisms of attachment and the efficacy of the soft tissue as a barrier. A healthy junctional epithelium (JE) served as positive control. RESULTS: No differences were observed in the rate of soft-tissue integration of immediate versus delayed implants; however, overall, mucosal integration took at least twice as long as osseointegration in this model. Qualitative assessment of Vimentin expression over the time course of soft-tissue integration indicated an initially disorganized peri-implant connective tissue envelope that gradually matured with time. Quantitative analyses showed significantly less total collagen in peri-implant connective tissues compared to connective tissue around teeth around implants. Quantitative analyses also showed a gradual increase in expression of hemidesmosomal attachment proteins in the peri-implant epithelium (PIE), which was accompanied by a significant inflammatory marker reduction. CONCLUSIONS: Within the timeframe examined, quantitative analyses showed that connective tissue maturation never reached that observed around teeth. Hemidesmosomal attachment protein expression levels were also significantly reduced compared to those in an intact JE, although quantitative analyses indicated that macrophage density in the peri-implant environment was reduced over time, suggesting an improvement in PIE barrier functions. Perhaps most unexpectedly, maturation of the peri-implant soft tissues was a significantly slower process than osseointegration.

Effects of implant placement timing and type of soft-tissue grafting on histological and histomorphometric outcomes in a preclinical canine model.

AIM: To determine the effects of implant timing and type of soft-tissue grafting on histological and histomorphometric outcomes in a preclinical model. MATERIALS AND METHODS: Four implant placement protocols were randomly applied at the mesial root sites of the third and fourth mandibular premolars in 10 mongrel dogs: immediate placement (group IP), early placement (group EP), delayed placement with/without alveolar ridge preservation (groups ARP and DP, respectively). A connective-tissue graft (CTG) or porcine-derived volume-stable collagen matrix (VCMX) was applied to enhance the ridge profile (simultaneously with implant placement in group IP and staged for others), resulting in five sites for each combination. All dogs were sacrificed 3 months after soft-tissue grafting. Histological and histomorphometric analyses were performed, and the data were analysed descriptively. RESULTS: CTG and VCMX were difficult to differentiate from the augmented area. The median total tissue thickness on the buccal aspect of the implant was largest in group IP/CTG (between 2.78 and 3.87 mm). The soft-tissue thickness was generally favourable with CTG at all implant placement timings. Within the DP groups, CTG yielded statistically significantly larger total and soft-tissue thickness than VCMX (p < .05). Among the groups with VCMX, group EP/VCMX showed the largest soft-tissue thickness at apical levels to the implant shoulder. CONCLUSIONS: CTG generally led to greater tissue thickness than VCMX.

Clinical outcomes of implant- versus abutment-level connection in screw-retained fixed dental prostheses: A 5-year randomized controlled trial.

AIM: The aim of the study was to evaluate the 5 years clinical outcomes associated with implant-level connection (IL) versus abutment-level connection (AL) for implants with an internal conical connection (ICC) supporting a screw-retained fixed partial denture. MATERIALS AND METHODS: Fifty patients with 119 implants were randomly allocated to either the AL or IL group. Radiographic (Marginal bone loss) and clinical outcomes (Bleeding on Probing, probing pocket depth, plaque accumulation, incidence of peri-implantitis and peri-implant mucositis as well as prosthetic complications) were collected and compared at 1, 2, 3, and 5 years. A linear mixed model was used to evaluate the differences between groups. RESULTS: Five years after treatment, the MBL change was not significantly different between the groups at any point. The MBL was 0.23 ± 0.64 mm (AL) and 0.23 ± 0.29 mm (IL). The bleeding on Probing was 44% (AL) and 45% (IL) (p = .89). The mean probing depth was 2.91 ± 1.01 mm (AL) and 3.51 ± 0.67 mm (IL). This difference between the groups was statistically significant but clinical insignificant. Presence of plaque was slightly higher (p = .06) in the IL group (34.4%) compared with the AL group (26.3%). The overall technical, biological, and prosthetic complication rates were similar between groups. None of the implants developed peri-implantitis during the entire follow-up period. CONCLUSION: The results of this clinical trial indicated that all clinical and radiographical parameters were clinically comparable between the study groups.