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Objective: To explore the effect of adding an allogenic soft tissue graft at time of single implant placement using a fully digital workflow for single implant placement and restoration without making either analog or digital impressions. Materials and methods: A prospective randomized clinical study was performed enrolling thirtynine participants requiring single tooth implant randomized into (+ graft) group which received an allogenic dermal graft at the time of implant placement (n=19), or (- graft) group (n=20). A fully digital surgical and restorative protocol was implemented. Intraoral scans were taken before implant placement (T0), at time of final crown delivery (T1) and at one-year post placement (T2). Intraoral scans were aligned using Geomagic Control X 2020 software), linear and volumetric changes in buccal tissues were measured at T0, T1 and T2. Implant survival, probing depths, and complications were recorded. Participants were asked to complete an OHIP-14 survey at T0 and T2. Marginal bone levels were measured at T0 and T2 on peri-apical x-rays. Results: 39 participants completed surgery and restoration in incisor, canine, premolar and molar positions. Two early failures were recorded in central incisor positions (95% survival). Crown delivery without complication from the digital workflow (impressionless) was achieved for 36/39 of cases (92%) with implant depth control being implicated as the chief challenge. Thirtyseven participants attended the one-year follow-up visit. Both groups showed gain in buccal tissues thickness without significant differences between the two groups for both linear and volumetric measurements (P>0.05). Soft tissue grafting was associated with minimal added morbidity. The interproximal marginal bone changes recorded were -0.16mm mesial and - 0.12mm distal for the graft group and -0.01mm mesial and -0.11mm distal for the non-graft group (p=0.07 for mesial and 0.83 for distal). OHIP score was significantly reduced at T2 compared to T0 (P=0.003) for the entire cohort. Conclusions: The augmentation of alveolar mucosa on the buccal aspect of single tooth implants is associated with clinically favorable outcomes. A fully digital workflow has been validated to permit crown delivery on CAD/CAM abutments without implant impressions. Keywords: Keywords: single implant, soft tissue graft, allograft, digital, marginal bone loss

Purpose: To investigate bone regeneration among three different bone graft materials in a rat calvarum model. Materials and Methods: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed. Results: At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis. Conclusions: Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model. Keywords: bone regeneration, calvarial defect, immunocytochemistry, micro-CT, osteoinduction

Purpose: This study sought to define the tissue responses at different implant-abutment interfaces by studying bone and peri-implant mucosal changes using a 5-year prospective randomized clinical trial design study. The conus interface was compared with the flat-to-flat interface and platform-switched implant-abutment systems. Materials and Methods: One hundred forty-one subjects were recruited and randomized to the three treatment groups according to defined inclusion and exclusion criteria. Following implant placement and immediate provisionalization in healed alveolar ridges, clinical, photographic, and radiographic parameters were measured at 6 months and annually for 5 years. The calculated changes in marginal bone levels, peri-implant mucosal zenith location, papillae lengths, and peri-implant Plaque Index and bleeding on probing were statistically compared. Results: Forty-eight conus interface implants, 49 flat-to-flat interface implants, and 44 platform-switched implants were placed in 141 subjects. Six platform-switched interface and eight flatto- flat interface implants failed, most of them within 3 months. After 5 years, 33 conical interface, 28 flat-to-flat interface, and 27 platform-switched interface implants remained for evaluation. Calculation of marginal bone level change showed a mean marginal bone loss of –0.16 ± 0.45 (–1.55 to 0.65), –0.92 ± 0.70 (–2.90 to 0.20), and –0.81 ± 1.06 (–3.35 to 1.35) mm for conical interface, flat-to-flat interface, and platform-switched interface implants, respectively (P < .0005). The peri-implant mucosal zenith changes were minimal for all three interface designs (0.10 mm and +0.08 mm, P > .60). Only 16% to 19% of the surfaces had presence of bleeding on probing, with no significant differences (P > .81) between groups. Interproximal tissue changes were positive and similar among the implant interface designs. Conclusion: Over 5 years, the immediate provisionalization protocol resulted in stable peri-implant mucosal responses for all three interfaces. Compared with the flat-to-flat and platform-switched interfaces, the conical interface implants demonstrated significantly less early marginal bone loss. The relationship of marginal bone responses and mucosal responses requires further experimental consideration. Keywords: esthetics, immediate loading, marginal bone levels, peri-implant mucosa, randomized controlled clinical trial

Agenesis of the permanent dentition is rare. This report describes a 20-yearold woman with 19 deciduous teeth, a single permanent mandibular premolar, and other physical traits associated with ectodermal dysplasia. The patient demonstrated esthetic parameters associated with maxillomandibular alveolar insufficiency, and her chief complaints were directed toward esthetics and the potential impact of restorative choices on function. Three typical options for restoration include overdentures, removable partial dentures, or implantsupported prostheses replacing her natural dentition. This report illustrates a fully integrated digital approach to treatment planning, the fabrication of a computer-aided design/computer-assisted manufacture surgical guide and provisional restoration, guided implant placement, and definitive restoration using monolithic zirconia implant-supported fixed dental prostheses. The lifelong management of this rehabilitation is an acknowledged challenge.

Peri-implantitis is a treatment-related complication with a biofilm-mediated pathogenesis. Several studies have demonstrated that the progression from peri-implant mucositis to peri-implantitis can be effectively managed by supportive implant therapy. However, the impact of implant prostheses on the evaluation of peri-implant tissues, the control of biofilm by oral hygiene and professional prophylaxis as well as the impact of cement or other prosthetic materials on peri-implant inflammation receive little attention. This report will consider prosthesis factors, abutment factors, and cement factors in the evaluation, management and prevention of peri-implantitis. The existing literature clearly indicates that mechanical disruption of dysbiotic biofilm is central to the prevention and management of peri-implantitis. Thus, prosthetic factors that enable or enhance biofilm formation or preclude its mechanical disruption may contribute to the progression of peri-implant mucositis to peri-implantitis. Unfortunately, many of the prosthetic factors that negatively impact peri-implant tissue health are the result of improper implant placement decisions. Both the surgical planning and prosthetic execution of therapy must be addressed in efforts to reduce the risk of peri-implantitis. Keywords: Peri-implantitis, oral hygiene, prosthesis, restorative space, cement

Regulation of cellular function is key to bone formation at endosseous implant surfaces. Osseointegration was "discovered" prior to the discovery of genetic regulation of osteoinduction or characterization of mesenchymal stem cells. Understanding osseointegration in cellular and molecular terms has benefited from genome-wide characterization of this healing process at endosseous implants in vivo. These in vivo studies also demonstrate a role for osteoprogenitor cells and cells involved in immune regulation and osteoclastogenesis. The identification of noncoding RNAs, including microRNAs, as key factors controlling cell function has highlighted the role of microRNAs in cell differentiation control. This review summarizes emerging in vitro and in vivo investigations emphasizing the role of microRNAs in the osseointegration process. Many microRNAs influence key osteoinductive pathways controlling Osterix, runt-related transcription factor 2 (RUNX2), and bone morphogenetic protein (BMP)/SMAD function. Others influence the monocyte/ macrophage lineage. While significant progress has been made in elucidating the mechanisms associated with the regulation of surface modulation of osteoblast differentiation by microRNAs, knowledge gaps are evident in the identification and characterization of microRNAs linked to osseointegration. Given existing knowledge regarding the varied expression of microRNAs and their role in inflammation, it is important to understand how microRNA expression may influence the process of bone accrual at implant surfaces during osseointegration. Keywords: bone remodeling, dental implants, implant surfaces, microRNAs, osseointegration

Purpose: The peri-implant bone and mucosa architecture contribute to the health and esthetics of singletooth dental implants. The implant-tooth distance (ITD) has been regarded as a key determinant of their outcomes. This study was conducted to determine the relationship between ITD and peri-implant bone, mucosa, and pink esthetic scores (PES) for anterior single-tooth implants. Materials and Methods: For 44 dental implants with a microthread conical abutment interface design placed in 38 participants, periapical radiographs and photographs were evaluated at 1 and 4 years to assess interproximal bone levels and PES. Results: Mean mesial and distal marginal bone level change over 4 years was 0.20 ± 1.00 mm and 0.20 ± 0.74 mm, respectively. In this cohort, there was no relationship between ITD and interproximal bone changes or papilla fill at 4 years; however, marginal bone changes influenced PES score-the smaller the ITD, the lower the PES (P < .001). Alone, ITD did not influence marginal bone levels or papilla in this cohort. Conclusion: These results imply a complex relationship between ITD, marginal bone levels, and PES scores for single-tooth implants. Keywords: implant-tooth distance, marginal bone loss, pink esthetic score, single tooth dental implant

Purpose: The goal of this investigation was to define time-dependent peri-implant tissue changes at implants with different abutment interface designs. Materials and Methods: Participants requiring replacement of single maxillary anterior and first premolar teeth were recruited and treated under an institutional review board (IRB)-approved protocol. Implants, titanium abutments, and provisional crowns were placed in healed ridges 5 months following preservation after tooth extraction with recombinant human bone morphogenetic protein-2 (rhBMP-2). Twelve weeks later, permanent crowns were placed on patient-specific abutments and evaluated at 6, 12, and 36 months following implant placement. Clinical and radiographic assessments of abutments and crowns, peri-implant mucosa, and marginal bone levels were recorded. Results: The 3-year assessment included 45 conical interface (CI), 34 flat-to-flat interface (FI), and 32 platform-switched interface (PS) implants in 111 participants. At 3 years, the mean marginal bone level (MBL) change at CI, FI, and PS implants was -0.12, -1.02, and -1.04 mm, respectively (P = .014). "Zero" MBL loss or gain was measured over the 3-year period at 72.1% CI, 3.0% FI, and 16.6% PS implants. There was a minor change (0.0 to 0.3 mm) in peri-implant mucosal zenith positions over time and between groups. Eighty percent of CI implants, 61% of FI implants, and 84% of PS implants were observed to have a clinically stable periimplant mucosal zenith position with less than 0.5 mm of measured recession. Over the 36-month period, there were no significant changes in the location of mesial or distal papilla in any group. Conclusion: Significant differences in MBLs were observed at different implant interfaces. Conical implant interfaces, but not flat-to-flat or platform-switched implant interfaces, were associated with no MBL changes over 3 years. Peri-implant mucosal stability was generally observed. The relationship of marginal bone responses and peri-implant mucosal stability requires further evaluation. Keywords: esthetics, immediate provisionalization, marginal bone levels, peri-implant mucosa

Purpose: To evaluate the influence that three different implant-abutment interface designs had on periimplant mucosal outcomes as assessed by the pink esthetic score (PES) 3 years after delayed implant placement and immediate provisionalization. Materials and Methods: Adult subjects (n = 141) requiring replacement of a bounded single tooth in the anterior maxilla as well as first premolar sites were randomized to receive one of three unique implant-abutment interface designs (conical interface [CI]; flat-to-flat interface [FI]; or platform-switch interface [PS]). Treatment included immediate provisionalization with prefabricated titanium abutments, followed by custom computer-aided design/computer-aided manufacturing (CAD/CAM) zirconia abutments and cement-retained, all-ceramic crowns delivered after 12 weeks. Bilateral (anterior sites) or unilateral (premolar sites) digital clinical photographs were made at 1, 3, 6, 12, 24, and 36 months post-implant placement. Five calibrated faculty evaluators who previously scored the 1-year PES image dataset scored the 24- and 36-month photographs using a digital, cloud-based tablet interface. Results: Six hundred ten clinical photographs were evaluated, resulting in a total of 3,050 sum PES values and 21,350 individual PES values. Faculty evaluator intrarater and interrater reliability were found to be "substantial," with intraclass correlation coefficient (ICC) values of 0.76 and 0.77, respectively. All three implant-abutment interface groups demonstrated acceptable esthetics at 3 years (mean sum PES = 10.1 ± 1.9, 4.0 to 13.2), with no single group demonstrating significantly greater mean sum PES values than another at the 3-year follow-up or at any recall interval in between. Conclusion: No significant differences were observed in mean sum PES scores for subjects randomized to one of three different implant-abutment interface geometries. Within the limitations of this study thus far, the first 6 months following definitive prosthesis delivery appear to still be the most significant with regard to improvement in PES outcomes for all three treatment groups. Keywords: esthetics, immediate provisionalization, implant-abutment interface, peri-implant mucosa

Purpose: To compare, by gene profiling analysis, the molecular events underscoring peri-implant mucosa formation at machined vs laser-microgrooved implant healing abutments. Materials and Methods: Forty endosseous implants were placed by a one-stage approach in 20 healthy subjects in nonadjacent sites for single-tooth restorations. In a split-mouth design, machined smooth and laser-microgrooved healing abutments were randomly assigned in each subject. Peri-implant mucosa adjacent to healing abutments was harvested by tissue punch biopsy at either 1, 2, 4, or 8 weeks following abutment placement. Total RNA was isolated from the peri-implant transmucosal soft tissues. A whole genome microarray using the Affymetrix Human Gene 2.1 ST Array was performed to describe gene expression profiles in relation to abutment topography and healing time duration. Data analysis was completed using GeneSpring software v.12.6. Results: Differential gene expression was revealed at all time points and among surfaces. Five hundred one genes were differentially expressed (fold change ≥ 2.0) at machined versus laser-modified abutments, and 459 of these were statistically significant (P ≤ .05). At 1 week, unique expression of IL-24 and MMP1 was observed in tissues from laser-treated surfaces. At 2, 4, and 8 weeks, mRNAs encoding keratins and protective proteins of cornified epithelium were upregulated in tissues from laser-modified abutments. At 4 weeks, upregulation (> 2-fold) of mRNAs encoding proteins associated with collagen fibril formation and function was observed in tissue from laser-modified abutments. In both tissues of machined and laser-modified abutments, mRNAs encoding junctional epithelium-specific proteins, ostogenic ameloblast associated protein (ODAM) and follicular dendritic cell secreted protein (FDCSP) were highly upregulated throughout weeks 2 to 8. Conclusion: Peri-implant abutment mucosal wound healing involves selective differentiation of epithelium and induction of the junctional epithelium. Laser-mediated alterations in abutment topography enhance collagen fibril-associated gene expression and alter epithelium/junctional epithelial gene expression. Clinically, shallower probing depths are measured at laser-mediated versus machined implant abutments. Keywords: dental implant abutment, junctional epithelium, laser, mucosal integration, titanium