In vivo preclinical study comparing the peri implant tissue of a minimally invasive implant using a flapless technique and a bone level implant using an open flap technique

In vivo preclinical study comparing the peri implant tissue of a minimally invasive implant using a flapless technique and a bone level implant using an open flap technique | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report In vivo preclinical study comparing the peri implant tissue of a minimally invasive implant using a flapless technique and a bone level implant using an open flap technique Aurore Barraco, Marie Paule Gustin, Guillaume Noel, Brigitte Grosgogeat, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6674437/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The purpose of the to test the hypothesis that the placement of a minimally invasive implant (MII) using a flapless technique provides a better quality of peri implant tissues compared to a reference implant (RI) placed with access flap in a canine model. Methods In this in vivo preclinical study 2 types of implants (MII without flap and RI with flap) were placed in both quadrants of the mandibula. Clinical, radiological, and histomorphometry measurements were performed at implant placement (T0), at healing abutment placement (T + 8W), and at the end of the study (T + 16W). Results A significant increase in keratinized tissue thickness was observed around MII (3.00mm ± 1.04 vs 3.68mm ± 0.63; p < 0.001) and a significant decrease for RI (3.47mm ± 0.74 vs 2.07mm ± 0.40; p < 0.05) between T0 and T + 16W. The biological width, in mesio-distal sections, was significantly greater around MII (mean ± SD PM-fBIC distances: 3680.5µm ± 629.2) than RI (2065.5µm ± 395.1, p < 0.001). Bone remodeling, in mesio-distal sections, around MII (mean ± SD IS-BC 890.4µm ± 759.2) was higher than the implant shoulder (IS) and was significantly greater than around RI (mean ± SD IS-BC -283.4µm ± 285.3, p < 0.001) for which significant bone resorption was observed around RI. Conclusion The present in vivo preclinical study found a greater thickness of the epithelial-connective tissue for MII compared to RI, which contributed to the formation of a biological space that promoted physiological tissue remodeling and supported favorable tissue stability; the hypothesis was therefore accepted. It would now be interesting to confirm these results in humans, particularly in the elderly and medically compromised patients for whom the atraumatic flapless surgical protocol seems particularly suitable. Dental implants Minimally invasive surgical procedures Osseointegration Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Just as keyhole surgery has transformed medical procedures, the development of minimally invasive techniques in dental implantology will enable better adaptation to the needs of an increasingly elderly and medically compromised population[ 1 – 3 ]. Indeed, minimally invasive techniques decrease the risk of per- or post-operative complications such as infections or hemorrhages, and shortens the healing period [ 4 ]. The flapless technique enhances patient post-surgical comfort through the use of an atraumatic surgical act, reduces the number of surgical procedures such as bone grafting, and the need to remove sutures or placing healing abutments [ 5 , 6 ]. These therefore help to reduce the cost and healing time of the treatment [ 4 , 7 – 9 ]. Several parameters are essential to ensure the a long-term survival of implants, especially in elderly, medically compromised or handicap patients, such as the quality and quantity of keratinized tissue around the implant [ 10 , 11 ]. Similarly, for long-term success of implants, the integrity of the biological width and thickness of the soft tissues are now considered a crucial parameter in order to avoid bacterial infiltration and bone loss [ 10 – 13 ]. These parameters might also be influenced by the surface treatment and the implant design [ 14 – 16 ]. In flapless surgery, another important parameter for long-term success is the level of implant embedding, in particular that of the machined smooth neck and the rough surface of one-piece implants. For instance, Hermann et al . have shown that a subcrestal placement of the machined smooth neck results in more crestal bone loss than equicrestal placement, and that supracrestal placement can lead to bone apposition [ 17 ]; however, subcrestal placement increases the vertical soft tissue thickness that creates a stronger barrier to bacterial infiltration by increasing the amount of keratinized tissue [ 18 ]. One of the limitations of flapless surgery is the need for precise implant positioning, especially the exact level of bone embedding that is difficult to control through lack of visibility of the bone crest (BC). For this reason, a new implant with a design adapted to flapless surgery was developed in 2008. This minimally invasive implant (MII) uses specific surgical protocols for predictable results that respect the peri-implant tissues. The purpose of the present in vivo study was to test the hypothesis that the placement of a MII using a flapless technique provides a better quality of peri implant tissues compared to a reference implant (RI) placed with access flap. MATERIALS AND METHODS Ethics statement This in vivo preclinical study was conducted in compliance with EU Directive 2010/63/EU for animal experiments and with ARRIVE guidelines [ 19 ]. The protocol of this study was submitted to the ethics committee of VetAgro Sup and authorized by the French ministry of higher education and research under project number APAFIS#6103-2016070511504068. Animals Five male beagle dogs (12 months-old and weighing approximately 10kg) with fully erupted permanent dentition were included. They were of the Marshall US strain, immunocompetent, not genetically modified, selected by the breeder on behavioral and size criteria, and were from the French site of Marshall BioRessources located in Gannat (Allier department, French administrative aera). During all experiments, the dogs were housed in cages maintained at 19 ± 2°C and 35%-70% humidity, with a 12/12h light/dark cycle). They were fed with a soft diet (SAFE® 326; Safe Lab®, Rosenberg, Germany) and water ad libitum . The experimental part of the study started after an adaptation period of 2 weeks. Control visits and tooth brushing were performed twice a week. The experimental protocol of the study is shown in Fig. 1 . Implants devices Two different types of implants were used in this study: a MII (MagiCore®, InnoBioSurg implant® Daejon, Republic of Korea) and a reference implant (RI; Nobel Parallel CC® Nobel Biocare®, Kloten, Switzerland). MII were 4mm in diameter and 7mm in length. This 1-piece titanium grade 5 sandblasted implant can be divided into 3 parts: a tapered body with 0.15mm-thick rectangular threads (Magic Fin Thread); a machined smooth neck (Cuff), with four different available heights chosen according to the gingival height that allows connective tissue and junctional epithelium adhesion; and a prosthetic platform to support the future prosthetic restoration (Post; Fig. 2 a). RI were 3.75mm in diameter and 7mm in length. This 2-piece titanium grade 4 anodized (TiUnite®) implant has conventional configuration (tapered, self-tapping, and triangular threads; Fig. 2 b). Surgical protocol All procedures were performed by an experimented surgeon, under sterile conditions and general anesthesia; the latter was induced using intravenous injection of ketamine (3mg/kg) and medetomidine (20µg/kg), and maintained using isoflurane inhalation. For each surgery, the dogs received an injection of amoxicillin once a day from the day before the surgery and for 7 days to prevent any infection, an oral cavity disinfection with chlorhexidine 0.2% and local anesthesia using articaine and 1:100 000 epinephrine. For pain control, the animals received 3 intravenous injections of morphine: for premedication, at the end of the procedure, and 4 hours after extubation (0.2mg/kg). A transcutaneous fentanyl patch was placed on the day of surgery (75µg/h). Meloxicam was given to the animals for 10 days (0.2mg/kg/d the first day and 0.1mg/kg/d the next 9 days). During the first surgery, the mandibular second, third and fourth premolars, along with the first molar were carefully extracted on both sides. After an 8-week healing period, a total of 30 implants (15 MII and 15 RI) were bilaterally and randomly placed in the mandible of each dog (Fig. 3a). However, the impossibility of taking a 3D intraoperative image, as recommended by the manufacturer, made it difficult to verify the correct bone embedding of the MII. Eight weeks after implant placement, healing abutments were connected to each implant with a small mid-crestal incision for RI. Flapless surgery was made for MII. For RI, a conventional 2-stage surgical protocol with a mucoperiosteal flap elevation and sequential drills for implant osteotomy were performed following the manufacturer’s instructions (Fig. 3b). Clinical analysis The height of keratinized tissue (mm) around the implant was clinically evaluated at 6 different probing points, and also on histological sections, after sacrificing the animals at the end of the study. Implant stability was measured using Periotest® (Dentisystem®, Bese, Hungary) at implant placement (T0), healing abutment placement (T + 8W), and at the end of the study (T + 16W) for the RI; this was also measured at the same time-points for MII. The Periotest® scale extends from − 8 to + 50 Periotest value (PTV); the lower the value, the greater the stability of the measured implant [ 20 ]. Before harvesting at T + 16W, peri-implant inflammation was measured using a periodontal probe scored using the Carter and Barnes’s Gingival Bleeding Index (0 = no bleeding, 1 = bleeding) [ 21 ]. Plaque Index was measured using the Loe and Silness’s plaque Index (0 = no plaque in the gingival area; 1 = presence of a film of plaque that may only be recognized by running a probe across the tooth surface; 2 = moderate accumulation of soft deposits which can be seen by the naked eye; 3 = abundance of plaque) [ 22 ]. Radiological analysis Intraoral radiographs were taken at implant placement (T0), at healing abutment placement (T + 8W), and at the end of the study (T + 16W). Angulators were customized (Unifast TRAD® resin; GC®, Lucerne, Switzerland) to ensure precise placement of receptors and standardize radiographs to minimize distortion and angulation errors. An image analysis program (ImageJ® v1.46h, National Institute of Health, Bethesda, MD, US) was used to superimpose the radiographs taken at implant placement (T0) and the end of the study (T + 16W) to measure the peri-implant marginal remodeling. This peri-implant marginal remodeling was calculated by the difference (mm) between the distance from the apex to the f BIC at the end of the study (T + 16W) compared to implant placement (T0). There was high agreement between the 2 examiners (reliability coefficient > 0.999). Sample collection and histologic preparation The animals were sacrificed 4 months after implant placement with an intravenous lethal dose of pentobarbital. The samples were then collected using a trephine under profuse saline irrigation and fixed with 2% glutaraldehyde − 2% paraformaldehyde in a sodium cacodylate buffer for 1 week. Dehydration was performed in serial steps of increasing ethanol concentration and the blocks were finally embedded in methyl methacrylate. Non-decalcified sections were prepared using a method adapted from Donath and Breuner [ 23 ]. Two cuts were performed for the polymerized blocks: 1 mesio-distal and 1 bucco-lingual, parallel to the long axis of each implant using a diamond wire saw. Then, the sections were obtained and reduced by micro grinding and polishing to a thickness of about 40µm. These sections were then superficially stained with a modified paragon stain and digitized for histomorphometric quantification. Histomorphometric analysis The images were analyzed by 2 different investigators (AB and CC) using ImageJ® (v1.46h, National Institute of Health). Before the analysis, the 2 investigators used randomly selected sessions from other animal studies for calibration. The following measurements were performed for each section and a mean was calculated on left and right side for the mesio-distal and bucco-lingual sections. The following landmarks were identified for linear measurements (µm): the marginal position of the peri-implant mucosa (PM); the apical termination of the pocket epithelium (aJE); the most coronal bone-to-implant contact ( f BIC); the top of the bone crest (BC); and the implant shoulder (IS; Fig. 4 ). The primary endpoint was the height of biological width (PM- f BIC). Secondary endpoints were bone resorption/apposition (IS-BC), in sections with BC above the IS a positive value (+) was given, whereas when BC was below IS a negative value (-) was used [ 24 ], hight of epithelial tissue (PM-aJE), hight of connective tissue (aJE- f BIC), the peri implant crestal bone level (IS- f BIC), and marginal bone level (BC- f BIC). The percentage of bone-to-implant contact (%BIC) was also calculated for each mesio-distal section; this corresponded to the percentage of the height of the bone in direct contact with the implant and the bone and the length of the total surface of the implant [ 25 ]. Statistical analysis To compare IS-BC between the 2 implants 15 values per implant were sufficient to have 80% power to detect an effect size of 0.80; a total of 5 dogs each with 6 implants were therefore used in the present study. To evaluate the inter-examiner reliability between the 2 investigators for the histomorphometric and radiographic analysis Lin’s concordance correlation coefficient for agreement on a continuous measure was calculated (function epi.ccc of R package Epi) [ 26 , 27 ]. Only the bias correction factor (C.b) that measures how far the best-fit line deviates from a line at 45 degrees is reported; no deviation from the 45-degree line occurs when C.b = 1. In case of good agreement, the mean of both values was conserved in the further analyses. Quantitative data were reported as mean with standard deviation (SD) and qualitative binary data as frequency with relative frequency, n (%). Ordinal data were treated as quantitative data. To compare quantitative data between implants, a linear mixed effects model was fitted with implant as explanatory variable and random intercept for dogs. Assumptions of models were checked. Fisher’s exact test was used to compare the distribution of binary data of both types of implants in clinical analysis. For all tests a p-value < 0.05 was considered significant. No adjustment was made for multiple comparisons as variables were interpreted separately regardless of time. Statistical analyses were performed using R language version 4.1.0 available at http://cran.r-project.org . RESULTS Clinical findings All the animals survived, and all the extracted teeth healed well before implant placement. Four of the 15 implants were not osseointegrated; all 4 were MII. The mean ± SD height of keratinized tissue around the MII significantly increased between implant placement (T0; 3.00mm ± 1.04) and end of study (T + 16W; 3.68mm ± 0.63; p < 0.001), and significantly decreased around the RI (3.47mm ± 0.74 vs. 2.07mm ± 0.40; p < 0.05; Table 1 , Fig. 5 ). There was no significant difference regarding bleeding and plaque indexes at the end of the study (T + 16W; Table 1 ). Table 1 Comparison of clinical parameters between RI and MII group at implant placement (T0) and end of study (T + 16W). Keratinized Tissue Height + (mm) n T0 n T + 16W RI 15 3.47 ± 0.74 15 2.07 ± 0.40* MII 12 3.00 ± 1.04 11 3.68 ± 0.63‡ Gingival bleeding index, n (%) RI 15 NA 5 (33.3) MII 12 NA 4 (33.3) Plaque index (%) RI 15 NA 1.27 ± 0.83 MII 12 NA 1.58 ± 1.16 Quantitative variables: mean ± SD; binary variable: n (%); T: Time; W: Weeks; NA: not applicable T0 vs T + 16W: *p < 0.05; ‡ p < 0.001 + Value measured clinically at T0 and histologically at T + 16W Both groups had excellent stability (from − 8 to 0 PTV) with no significant difference between MII and RI at implant placement (T0) and end of study (T + 16W), but there was a significantly greater stability in the RI group at healing abutment placement (T + 8W; mean PTV: -4.14 ± 1.73 vs -1.83 ± 3.01, p < 0.01; Table 2 ). Table 2 Comparison of primary stability parameter between RI and MII group at the different follow-up times. Time period Primary stability (PTV) n T0 n T + 8W n T + 16W RI 15 -3.80 ± 1.56 15 -4.14 ± 1.73 15 -3.12 ± 1.22 MII 15 -3.38 ± 1.97 12 -1.83 ± 3.01† 12 -2.11 ± 2.59 Comparison of RI and MII groups at each follow-up time: † P < 0.01, PTV: Periotest Value; T: Time; W: Weeks. Radiological findings Peri-implant bone remodeling (apex- f BIC) between implant placement (T0) and end of study (T + 16W) was significantly higher around MII (mean ± SD bone level difference 2.58mm ± 1.97) than around RI (0.63mm ± 0.36, p < 0.001; Table 3 ) Table 3 Results from radiological measurements of the peri-implant bone remodeling (Apex- f BIC) at the implant placement (T0) versus at the end of the study (T + 16W). RI MII Bone remodeling (Apex- f BIC) (mm) 0.63 ± 0.36 2.58 ± 1.97 ‡ mean ± SD (mm). ‡ p < 0.001 Histological findings Inter-examiner reliability between the 2 investigators (AB and CC) was high (C.b = 0.999). Soft tissue behavior For soft tissue mesio-distal sections, the mean ± SD PM- f BIC (3680.5µm ± 629.2 vs. 2065.5µm ± 395.1, p < 0.001) and PM-aJE distances (2327.1µm ± 322.9 vs. 889.9µm ± 435.1, p < 0.001) were significantly greater for MII than for RI. There was no significant difference in aJE- f BIC between the 2 groups. For bucco-lingual sections there was no significant difference between the 2 groups in terms of PM- f BIC, PM-aJE, and aJE- f BIC (Table 4 and Fig. 6 ). Table 4 Histomorphometric findings at end of study (T + 16W). n RI n MII Mesio- distal section PM- f BIC (µm) 15 2065.5 ± 395.1 11 3680.5 ± 629.2 ‡ IS-BC (µm) 15 -283.4 ± 285.3 11 890.4 ± 759.2 ‡ PM-aJE (µm) 15 889.9 ± 435.1 11 2327.1 ± 322.9‡ aJE- f BIC (µm) 15 1175.8 ± 358.3 11 1353.3 ± 513.3 (p = 0.29) IS- f BIC (µm) 15 655.2 ± 276.5 11 802.9 ± 646.2 (p = 0.44) BC- f BIC (µm) 15 400.3 ± 162.1 11 1692.3 ± 671.4 ‡ BIC (%) 15 0.695 ± 0.147 11 0.517 ± 0.251 * Bucco-lingual section PM- f BIC (µm) 13 3064.0 ± 948.8 10 2889.6 ± 989.7 (p = 0.67) IS-BC (µm) 15 1424.9 ± 1039.0 12 253.6 ± 1200.5 † PM-aJE (µm) 12 1516.7 ± 631.8 10 1532.0 ± 775.8 (p = 0.96) aJE- f BIC (µm) 13 1611.4 ± 949.8 10 1357.9 ± 546.6 (p = 0.46) IS- f BIC (µm) 15 1466.8 ± 1056.2 12 940.6 ± 1070.4 (p = 0.20) BC- f BIC(µm) 15 41.8 ± 170 12 687 ± 506.3 ‡ n: number of samples analyzed; Mean ± standard deviation (µm) and comparison of MII and RI groups *p < 0.05; † p < 0.01; ‡ p < 0.001; negative values maybe observed for IS/BC distance as the BC point maybe located below the IS point. Epithelial tissue (PM-aJE), connective tissue (aJE- f BIC), biological width (PM- f BIC), peri implant crestal and marginal bone levels (BC- f BIC, IS- f BIC, and IS-BC), and the bone-implant contact (%BIC) Hard tissue behavior For bone remodeling in mesio-distal sections, the mean ± SD IS-BC distance was negative for RI (-283.4µm ± 285.3) and positive for MII (890.4µm ± 759.2), and there was a significant difference between these values (p < 0.001). The mean ± SD BC- f BIC was significantly greater for MII (1692.3µm ± 671.4) than for RI (400.3µm ± 162.1, p < 0.001). For bone remodeling in bucco-lingual sections, the mean ± SD IS-BC distance was significantly greater for RI (1424.9µm ± 1039.0) than MII (253.6µm ± 1200.5, p < 0.01; Table 4 and Fig. 6 ). There was a trend towards a greater mean ± SD IS- f BIC distance for RI (1466.8µm ± 1056.2) than MII (940.6µm ± 1070.4, p = 0.20), and the mean ± SD BC- f BIC distance was significantly greater in MII (687µm ± 506.3) than RI (41.8µm ± 170, p < 0.001; Table 4 ). The mean %BIC was significantly greater for RI (0.695µm ± 0.147) than for MII (0.517µm ± 0.251, p < 0.05; Table 4 ). DISCUSSION The results of this in vivo preclinical study indicate that hard and soft tissue behavior differed between MII and RI. These differences may be explained by the design of the implants tested, in particular the tissue behavior around the machined smooth neck of the MII. Regarding hard tissue behavior, it is now well established that the absence of thread exposure, peri-implant tissue thickness, and position of the micro-gap between the collar and the prosthesis improve the stability of peri-implant tissues [ 28 ]. Bone quality is also pivotal; Simons et al . reported that early crestal bone loss around the neck of mandibular implants was greater when the bone was cortical rather than cancellous [ 29 ]. For bone level implants, platform switching and the platform-neck design reduces the risk of exposure of rough threads and the occurrence of peri-implantitis [ 16 , 30 , 31 ]. Regarding 1-piece implants, such as the MII, the absence of a microgap limits the risk of bone resorption. In the present study, for the IS-BC we observed a negative mean value for the RI and positive mean value for the MII in mesio-distal sections. No significant difference was found when considering only the IS- f BIC distance in mesio-distal sections, but the results seemed to show a lower bone resorption in bucco-lingual sections around MII. The RI were placed at the bone crest level and the machined smooth neck of MII were placed subcrestally. However, at T + 16W an apical displacement of the crestal bone was observed around RI compared to MII (IS-BC). Consequently, the bone crest was higher around the MII and could favor a thicker biological width around MII implants, which was confirmed by the significantly greater mean values of PM-aJE and PM- f BIC on mesio-distal sections. It is of note that several authors have reported that there is no significant difference in osseointegration and peri-implant bone remodeling between 2 stage and 1 stage (with flap) surgical protocols with similar placement depth [ 32 – 34 ]. The observed differences in the present study could be explained by the use of a flapless technique for MII, however intraoperative 3D images that are part of the protocol, were not possible in this animal study. Consequently, the level of bone embedding of the rough surface of the MII implant could only be assessed using 2D imaging. As a result, we cannot exclude the possibility that some threads were positioned outside the bone in the vestibulo-lingual dimension, particularly in areas with narrow bone ridges. In addition, the oral intubation of the dogs made it impossible to check the existence of any occlusal contacts resulted in occlusal contact between the antagonist teeth and the MII. The differences in crestal bone remodeling between MII and RI is in accordance with that reported by Hermann et al . who found significant cortical bone resorption on a smooth neck when comparing bone level and tissue level implants [ 17 , 35 – 37 ], but also with a meta-analysis that found that the marginal bone loss around rough threaded neck implants was significantly less than around the machined smooth neck in subcrestal placement [ 38 ]. This was confirmed by the radiological findings herein that showed peri-implant bone remodeling (apex- f BIC) between implant placement (T0) and end of study (T + 16W) was significantly greater around MII than around RI. As described in the literature, only gingival cells can adhere to the smooth neck and the bone initially present around the collar was replaced by soft tissues [ 39 , 40 ] as found herein. The resultant larger epithelio-conjunctival attachment for MII could create a barrier to bacterial infiltration. Furthermore, the clinical results show a reduced thickness of keratinized tissue at implant placement (T0) around MII, which can be explained by the removal of keratinized tissue in the MII surgical protocol (Magic drill trephine). But after tissue maturation at T + 16W the results are inversed, the keratinized tissue was significantly thicker around MII. This observation was confirmed by the histological results that showed a higher mean soft tissue height around MII between implant placement (T0) and end of study (T + 16W) whereas there was a significant mean soft tissue reduction around RI. This phenomenon may indicate that a minimally invasive procedure along with a 1-piece smooth neck implant develop a sufficiently dense epithelial barrier and thick keratinized soft gingival tissue to prevent peri-implantitis [ 41 ]. This hypothesis is supported by the results of an in vitro study reported by Attik et al . showing that adhesion and proliferation of human gingival fibroblasts are higher on the MII than on the RI under the scanning electron microscopy [ 16 ]. However, this difference may be reduced by the new smooth anodized surface at the neck of the RI (Xeal ® surface replacing the rough TiUnit ® surface) that allows the attachment of gingival soft tissues [ 42 , 43 ] to create a protective barrier on the underlying bone and improve long-term soft tissue stability [ 44 ]. For %BIC, the differences in surface treatment and thread design of RI and MII can explain the observed differences, as reported by Abrahamsson et al . who found that micro-thread implants had a larger %BIC in comparison to macro-thread implants [ 45 ]. In addition, the absence of significant difference in the mean bleeding index score between the 2 groups suggests that neither implant is more favorable for the development of a peri-implant inflammation. The greater frequency of Plaque Index 3 on MII can be explained by the wide MII platform design, compared to RI, which could be of importance as it is recognized that the presence of plaque leads to more bone resorption [ 46 , 47 ]. Concerning implant stability, the significant increase observed at healing abutment placement (T + 8W) for RI can be explained by the difference in thread design and the implantation protocol; RI self-tapping implants obtain stability through undersized drilling and cortical bone compression in contrast with the adjusted implantation without bone compression (Magic Fin Thread) by fine morphological contact in cancellous bone of the MII. Furthermore, the study reported by Coutant et al . showed that the primary stability of Magic Fin Thread was compatible with clinical osseointegration in sinus sites with severe bone atrophy (posterior maxillary areas with type IV bone and residual bone height 4 mm) [ 48 ]. Limitations The aim of this in vivo preclinical study was to compare 2 different surgical protocols (with and without the opening of a flap) and these differed in 3 aspects (submerged versus transgingival healing, flap versus no flap, and different implant designs), which could be considered to be a limitation. We deliberately did not confine ourselves to comparing 2 different implant designs (bone level vs tissue level) or different levels of implant embedding, rather we investigated the advantages of placing an MII in terms of tissue quality, compared to a RI placed using conventional flap surgery. The comparison of identical mucosal healing between the 2 implants would only be possible if the RI implants and abutment were placed at the same time. We chose to follow the standard protocol for placing a BL implant with two surgical steps. This procedure is used clinically where RI implants can be put into function from 8 weeks according to the available data. This decision can indeed be considered as a limitation for soft tissue healing. Another limitation is the absence of 3D imaging and intubation through the mouth of the dogs, which could have influenced the results; however, unlike this animal study, clinicians who use MII will be able to verify the implant depths; furthermore, the canine model does not allow the assessment of infectious and hemorrhagic risk factors and therefore it is difficult to generalize the results to medically compromised patients. A clinical study targeted this population, respecting the MII insertion protocol and using 3D imaging, could be conducted to verify the results of the present study. CONCLUSION The present in vivo preclinical study found a greater thickness of the epithelial-connective tissue for MII compared to RI, which contributed to the formation of a biological space that promoted physiological tissue remodeling and supported favorable tissue stability, thereby the hypothesis was accepted. It would now be interesting to confirm these results in humans, particularly in the elderly and medically compromised patients for whom the atraumatic flapless surgical protocol seems particularly suitable. Abbreviations MII minimally invasive implant RI reference implant fBIC first Bone to Implant Contact IS Implant Shoulder BC Bone Crest aJE apical Junction Epithelial PM Peri implant Mucosa EU European Union ARRIVE guidelines Animal Research:Reporting of In Vivo Experiments APAFIS Authorization number for projects using animals for scientific purposes C.b bias correction factor SD Standard Deviation Declarations Conflict of Interest: The authors have stated explicitly that there are no conflicts of interest in connection with this study. Sources of Funding Statement This study was supported by an industrial partnership with InnoBioSurg (Daejon, Republic of Korea) Ethics approval All applicable international guidelines for the care and use of animals were complied with according to the Institutional Animal Care Guidelines of the French National ministry of research Author Contribution A.B., B.G. and A.L. wrote the main manuscript. G.N. supervised the animal study, MPG made statistical analysis, A.L. reviewed the manuscript Acknowledgments: The authors would like to thank Philip Robinson (DRS, Hospices Civils de Lyon) for manuscript preparation. References Arısan V, Bölükbaşı N, Öksüz L. Computer-assisted flapless implant placement reduces the incidence of surgery-related bacteremia. Clin Oral Investig. 2013 Dec;17(9):1985–93. Dudley J. Implants for the ageing population. Aust Dent J. 2015 Mar;60 Suppl 1:28–43. Vissink A, Spijkervet F, Raghoebar GM. 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Effect of history of periodontitis on implant success: meta-analysis and systematic review. Implant Dent. 2014 Dec;23(6):687–96. Zheng Z, Ao X, Xie P, Jiang F, Chen W. The biological width around implant. J Prosthodont Res. 2021 Feb 24;65(1):11–8. Doornewaard R, Christiaens V, De Bruyn H, Jacobsson M, Cosyn J, Vervaeke S, et al. Long-Term Effect of Surface Roughness and Patients’ Factors on Crestal Bone Loss at Dental Implants. A Systematic Review and Meta-Analysis. Clin Implant Dent Relat Res. 2017 Apr;19(2):372–99. Rakic M, Galindo-Moreno P, Monje A, Radovanovic S, Wang HL, Cochran D, et al. How frequent does peri-implantitis occur? A systematic review and meta-analysis. Clin Oral Investig. 2018 May;22(4):1805–16. Attik N, Phantarasmy M, Abouelleil H, Chevalier C, Barraco A, Grosgogeat B, et al. Comparison of the Biological Behavior and Topographical Surface Assessment of a Minimally Invasive Dental Implant and a Standard Implant: An In Vitro Study. Materials (Basel). 2022 Oct 27;15(21):7540. Hermann JS, Jones AA, Bakaeen LG, Buser D, Schoolfield JD, Cochran DL. Influence of a machined collar on crestal bone changes around titanium implants: a histometric study in the canine mandible. J Periodontol. 2011 Sep;82(9):1329–38. Longoni S, Tinto M, Pacifico C, Sartori M, Andreano A. Effect of Peri-implant Keratinized Tissue Width on Tissue Health and Stability: Systematic Review and Meta-analysis. Int J Oral Maxillofac Implants. 2019 Dec;34(6):1307–17. Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020 Jul;18(7):e3000410. Oh JS, Kim SG, Lim SC, Ong JL. A comparative study of two noninvasive techniques to evaluate implant stability: Periotest and Osstell Mentor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Apr;107(4):513–8. Carter HG, Barnes GP. The Gingival Bleeding Index. J Periodontol. 1974 Nov;45(11):801–5. Löe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol. 1967 Dec;38(6):Suppl:610-616. Donath K, Breuner G. A method for the study of undecalcified bones and teeth with attached soft tissues. The Säge-Schliff (sawing and grinding) technique. J Oral Pathol. 1982 Aug;11(4):318–26. Souza AB, Alshihri A, Kämmerer PW, Araújo MG, Gallucci GO. Histological and micro-CT analysis of peri-implant soft and hard tissue healing on implants with different healing abutments configurations. Clin Oral Implants Res. 2018 Oct;29(10):1007–15. Babuska V, Moztarzadeh O, Kubikova T, Moztarzadeh A, Hrusak D, Tonar Z. Evaluating the osseointegration of nanostructured titanium implants in animal models: Current experimental methods and perspectives (Review). Biointerphases. 2016 Sep 15;11(3):030801. Lin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics. 1989 Mar;45(1):255–68. Liao JJZ, Lewis JW. A Note on Concordance Correlation Coefficient. PDA Journal of Pharmaceutical Science and Technology. 2000 Jan 1;54(1):23–6. Baixe S, Tenenbaum H, Etienne O. [Microbial contamination of the implant-abutment connections: Review of the literature]. Rev Stomatol Chir Maxillofac Chir Orale. 2016 Feb;117(1):20–5. Simons WF, De Smit M, Duyck J, Coucke W, Quirynen M. The proportion of cancellous bone as predictive factor for early marginal bone loss around implants in the posterior part of the mandible. Clin Oral Implants Res. 2015 Sep;26(9):1051–9. Macedo P, Pereira J, Vahey B, Henriques B, Benfatti C, Magini R, et al. Morse taper dental implants and platform switching: The new paradigm in oral implantology. European journal of dentistry. 2016 Mar [cited 2022 Sep 24];10(1). Santiago JF, Batista VE de S, Verri FR, Honório HM, de Mello CC, Almeida DA dF, et al. Platform-switching implants and bone preservation: a systematic review and meta-analysis. Int J Oral Maxillofac Surg. 2016 Mar;45(3):332–45. Chrcanovic BR, Albrektsson T, Wennerberg A. Immediately loaded non-submerged versus delayed loaded submerged dental implants: a meta-analysis. Int J Oral Maxillofac Surg. 2015 Apr;44(4):493–506. Al Amri MD. Crestal bone loss around submerged and nonsubmerged dental implants: A systematic review. J Prosthet Dent. 2016 May;115(5):564-570.e1. Moustafa Ali RM, Alqutaibi AY, El-Din Gomaa AS, Abdallah MF. Effect of Submerged vs Nonsubmerged Implant Placement Protocols on Implant Failure and Marginal Bone Loss: A Systematic Review and Meta-Analysis. Int J Prosthodont. 2018 Feb;31(1):15–22. Hermann JS, Cochran DL, Nummikoski PV, Buser D. Crestal bone changes around titanium implants. A radiographic evaluation of unloaded nonsubmerged and submerged implants in the canine mandible. J Periodontol. 1997 Nov;68(11):1117–30. Hermann JS, Buser D, Schenk RK, Cochran DL. Crestal bone changes around titanium implants. A histometric evaluation of unloaded non-submerged and submerged implants in the canine mandible. J Periodontol. 2000 Sep;71(9):1412–24. Hermann JS, Schoolfield JD, Schenk RK, Buser D, Cochran DL. Influence of the size of the microgap on crestal bone changes around titanium implants. A histometric evaluation of unloaded non-submerged implants in the canine mandible. J Periodontol. 2001 Oct;72(10):1372–83. Zhang Q, Yue X. Marginal Bone Loss around Machined Smooth Neck Implants Compared to Rough Threaded Neck Implants: A Systematic Review and Meta-Analysis. J Prosthodont. 2021 Jun;30(5):401–11. Schwarz F, Hegewald A, Becker J. Impact of implant-abutment connection and positioning of the machined collar/microgap on crestal bone level changes: a systematic review. Clin Oral Implants Res. 2014 Apr;25(4):417–25. Koodaryan R, Hafezeqoran A. Evaluation of Implant Collar Surfaces for Marginal Bone Loss: A Systematic Review and Meta-Analysis. Biomed Res Int. 2016;2016:4987526. Berglundh T, Lindhe J, Ericsson I, Marinello CP, Liljenberg B, Thomsen P. The soft tissue barrier at implants and teeth. Clin Oral Implants Res. 1991;2(2):81–90. Crenn MJ, Lefort L, Brazuna RP, Dubot P, Giorgi ML, Peyre P. Anodized SLM Ti6Al4V surfaces: influence of surface characteristics on NTs growth and resulted surfaces properties. J Mater Chem B. 2024 Nov 13;12(44):11502–14. Susin C, Finger Stadler A, Fiorini T, de Sousa Rabelo M, Ramos UD, Schüpbach P. Safety and efficacy of a novel anodized abutment on soft tissue healing in Yucatan mini-pigs. Clin Implant Dent Relat Res. 2019 Mar;21 Suppl 1:34–43. Rompen E, Domken O, Degidi M, Pontes AEF, Piattelli A. The effect of material characteristics, of surface topography and of implant components and connections on soft tissue integration: a literature review. Clin Oral Implants Res. 2006 Oct;17 Suppl 2:55–67. Abrahamsson I, Berglundh T. Tissue characteristics at microthreaded implants: an experimental study in dogs. Clin Implant Dent Relat Res. 2006;8(3):107–13. Pranskunas M, Poskevicius L, Juodzbalys G, Kubilius R, Jimbo R. Influence of Peri-Implant Soft Tissue Condition and Plaque Accumulation on Peri-Implantitis: a Systematic Review. J Oral Maxillofac Res. 2016 Sep;7(3):e2. Monje A, Insua Brandariz A, Wang HL. Understanding Peri-Implantitis as a Plaque-Associated and Site-Specific Entity: On the Local Predisposing Factors. J Clin Med. 2019 Feb 25;8:279. Coutant JC, Canepa C, Naveau A, Sedarat C, Lauverjat Y, Ella B. Evaluation of thin-threaded implants primary stability in type IV bone right after maxillary sinus floor elevation: A human cadaver study. J Prosthodont. 2024 Nov 14; Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6674437","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":467976621,"identity":"f8a684aa-7e40-4e35-b861-ef178444d1a6","order_by":0,"name":"Aurore Barraco","email":"","orcid":"","institution":"Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"Aurore","middleName":"","lastName":"Barraco","suffix":""},{"id":467976622,"identity":"9230d6e8-eb52-4faf-a39d-8ef2d55451dd","order_by":1,"name":"Marie Paule Gustin","email":"","orcid":"","institution":"Université Lyon 1, Équipe Biostatistique Santé, UMR CNRS 5558","correspondingAuthor":false,"prefix":"","firstName":"Marie","middleName":"Paule","lastName":"Gustin","suffix":""},{"id":467976623,"identity":"0a9eefc0-aa12-44db-aac6-65b7a8ecba47","order_by":2,"name":"Guillaume Noel","email":"","orcid":"","institution":"University of Lyon Marcy l’Etoile","correspondingAuthor":false,"prefix":"","firstName":"Guillaume","middleName":"","lastName":"Noel","suffix":""},{"id":467976624,"identity":"3c688ecd-d369-4599-ab54-f238b8a7f728","order_by":3,"name":"Brigitte Grosgogeat","email":"","orcid":"","institution":"Universite de Lyon, Université Lyon 1, UMR CNRS 5615","correspondingAuthor":false,"prefix":"","firstName":"Brigitte","middleName":"","lastName":"Grosgogeat","suffix":""},{"id":467976625,"identity":"08833874-c426-4754-8f2b-21e4539b2904","order_by":4,"name":"Arnaud Lafon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIie3QsUoDMRzH8V+IxOWvt+ZIub7ClULxQOmrFASd6ng4yYGQqQ/QUsHXcLxSyHTe3EEQEZwcWlwElyZXHJS7qpuUfLd/+H9ICODz/dsEWuA5sAQI4Jk9ktjPthOCGICNK8Lc7hEo/wXhVE0VuWwkwfR+9kYpKNDcPJ/oh1acMy1XdxKk6o0sL04VlSBpxHl3qF/IkXBSWHI4qL+moFgdaPuwx1FPDfWcwtsnbU8k+lQv2gV1PxxpG+qpxJGMbQg1kLiwm47EjjBLAvxAOpYkN6WkjhFn4aisyHUy0ZKaSGQftnhNj6PIcCPf03lfgM8WK30VNZHPj/sy7blxO/geX/5p3efz+Xa9NV96SVvg7QNaAAAAAElFTkSuQmCC","orcid":"","institution":"Universite de Lyon, Université Lyon 1, UMR CNRS 5615","correspondingAuthor":true,"prefix":"","firstName":"Arnaud","middleName":"","lastName":"Lafon","suffix":""}],"badges":[],"createdAt":"2025-05-15 16:23:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6674437/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6674437/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84329146,"identity":"5754ff81-dff7-44fe-ba59-63dd5248475f","added_by":"auto","created_at":"2025-06-10 15:39:17","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39702,"visible":true,"origin":"","legend":"\u003cp\u003eExperimental protocol (T: Time; W: Weeks).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6674437/v1/eb6d51cc52c84cf3dbe1fa9d.jpg"},{"id":84329145,"identity":"7cc0ec44-eaca-457d-abe0-dfcca2afdd43","added_by":"auto","created_at":"2025-06-10 15:39:17","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":20964,"visible":true,"origin":"","legend":"\u003cp\u003ea) Minimally invasive implant (MII) MagiCore\u003csup\u003e®\u003c/sup\u003e implant: tissue level implant with fin rectangular threads (Magic Fin Thread), a machined smooth neck (Cuff), and a prosthetic platform (Post); b) Nobel Parallel CC\u003csup\u003e®\u003c/sup\u003e implant: bone level implant with conventional triangular threads.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6674437/v1/fa793cfc3a5783a9531e790c.jpg"},{"id":84329720,"identity":"250a538b-1f05-4fe4-a082-b18123196091","added_by":"auto","created_at":"2025-06-10 15:47:18","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":84122,"visible":true,"origin":"","legend":"\u003cp\u003ea) Implant placement (T0); b) healing abutment placement (T+8W) with RI on sites 1 and 3, and MII on site 2.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6674437/v1/4edf0f1382dc8169a9ee1c34.jpg"},{"id":84329148,"identity":"f5eb1c08-e930-4ec0-92be-08c6aac2f6a6","added_by":"auto","created_at":"2025-06-10 15:39:18","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":51847,"visible":true,"origin":"","legend":"\u003cp\u003eMesio-distal section of a) RI and b) MII with the following landmarks: PM, the marginal position of the peri-implant mucosa; aJE, the apical termination of the pocket epithelium; fBIC, the most coronal bone-to-implant contact; BC, the top of the bone crest; IS, the implant shoulder.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6674437/v1/6ab54d52c95f413e91c22b92.jpg"},{"id":84329150,"identity":"3f16e8bb-aa1f-4414-8772-d53fcf9f4a51","added_by":"auto","created_at":"2025-06-10 15:39:18","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":25324,"visible":true,"origin":"","legend":"\u003cp\u003eHeight of keratinized tissue between RI and MII groups at inclusion and T+16W. The circles and the vertical bars correspond to the mean and the standard deviation, respectively.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6674437/v1/20a9e2ba2189eced5f17d1ac.jpg"},{"id":84329152,"identity":"63ef25ab-d43c-4b55-a8e2-667683bc7ec1","added_by":"auto","created_at":"2025-06-10 15:39:18","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":24898,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of histological parameters between RI and MII group at T+16W for biological width (PM-fBIC) and marginal bone level (IS-BC) in mesio-distal sections. Error bars are SD.\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6674437/v1/7b841973f2709bfe5b9d75d9.jpg"},{"id":86135984,"identity":"cf0a9cd8-741b-4aef-a19b-8f2ed932c1da","added_by":"auto","created_at":"2025-07-07 07:47:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":996442,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6674437/v1/cbf08d83-9091-4ec7-b780-889eca532a21.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"In vivo preclinical study comparing the peri implant tissue of a minimally invasive implant using a flapless technique and a bone level implant using an open flap technique","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eJust as keyhole surgery has transformed medical procedures, the development of minimally invasive techniques in dental implantology will enable better adaptation to the needs of an increasingly elderly and medically compromised population[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Indeed, minimally invasive techniques decrease the risk of per- or post-operative complications such as infections or hemorrhages, and shortens the healing period [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe flapless technique enhances patient post-surgical comfort through the use of an atraumatic surgical act, reduces the number of surgical procedures such as bone grafting, and the need to remove sutures or placing healing abutments [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These therefore help to reduce the cost and healing time of the treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral parameters are essential to ensure the a long-term survival of implants, especially in elderly, medically compromised or handicap patients, such as the quality and quantity of keratinized tissue around the implant [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Similarly, for long-term success of implants, the integrity of the biological width and thickness of the soft tissues are now considered a crucial parameter in order to avoid bacterial infiltration and bone loss [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These parameters might also be influenced by the surface treatment and the implant design [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In flapless surgery, another important parameter for long-term success is the level of implant embedding, in particular that of the machined smooth neck and the rough surface of one-piece implants. For instance, Hermann \u003cem\u003eet al\u003c/em\u003e. have shown that a subcrestal placement of the machined smooth neck results in more crestal bone loss than equicrestal placement, and that supracrestal placement can lead to bone apposition [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]; however, subcrestal placement increases the vertical soft tissue thickness that creates a stronger barrier to bacterial infiltration by increasing the amount of keratinized tissue [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. One of the limitations of flapless surgery is the need for precise implant positioning, especially the exact level of bone embedding that is difficult to control through lack of visibility of the bone crest (BC). For this reason, a new implant with a design adapted to flapless surgery was developed in 2008. This minimally invasive implant (MII) uses specific surgical protocols for predictable results that respect the peri-implant tissues.\u003c/p\u003e \u003cp\u003eThe purpose of the present \u003cem\u003ein vivo\u003c/em\u003e study was to test the hypothesis that the placement of a MII using a flapless technique provides a better quality of peri implant tissues compared to a reference implant (RI) placed with access flap.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthics statement\u003c/h2\u003e \u003cp\u003eThis \u003cem\u003ein vivo\u003c/em\u003e preclinical study was conducted in compliance with EU Directive 2010/63/EU for animal experiments and with ARRIVE guidelines [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The protocol of this study was submitted to the ethics committee of VetAgro Sup and authorized by the French ministry of higher education and research under project number APAFIS#6103-2016070511504068.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAnimals\u003c/h3\u003e\n\u003cp\u003eFive male beagle dogs (12 months-old and weighing approximately 10kg) with fully erupted permanent dentition were included. They were of the Marshall US strain, immunocompetent, not genetically modified, selected by the breeder on behavioral and size criteria, and were from the French site of Marshall BioRessources located in Gannat (Allier department, French administrative aera). During all experiments, the dogs were housed in cages maintained at 19\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u0026deg;C and 35%-70% humidity, with a 12/12h light/dark cycle). They were fed with a soft diet (SAFE\u0026reg; 326; Safe Lab\u0026reg;, Rosenberg, Germany) and water \u003cem\u003ead libitum\u003c/em\u003e. The experimental part of the study started after an adaptation period of 2 weeks. Control visits and tooth brushing were performed twice a week. The experimental protocol of the study is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003eImplants devices\u003c/h3\u003e\n\u003cp\u003eTwo different types of implants were used in this study: a MII (MagiCore\u0026reg;, InnoBioSurg implant\u0026reg; Daejon, Republic of Korea) and a reference implant (RI; Nobel Parallel CC\u0026reg; Nobel Biocare\u0026reg;, Kloten, Switzerland). MII were 4mm in diameter and 7mm in length. This 1-piece titanium grade 5 sandblasted implant can be divided into 3 parts: a tapered body with 0.15mm-thick rectangular threads (Magic Fin Thread); a machined smooth neck (Cuff), with four different available heights chosen according to the gingival height that allows connective tissue and junctional epithelium adhesion; and a prosthetic platform to support the future prosthetic restoration (Post; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). RI were 3.75mm in diameter and 7mm in length. This 2-piece titanium grade 4 anodized (TiUnite\u0026reg;) implant has conventional configuration (tapered, self-tapping, and triangular threads; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u003c/p\u003e\n\u003ch3\u003eSurgical protocol\u003c/h3\u003e\n\u003cp\u003eAll procedures were performed by an experimented surgeon, under sterile conditions and general anesthesia; the latter was induced using intravenous injection of ketamine (3mg/kg) and medetomidine (20\u0026micro;g/kg), and maintained using isoflurane inhalation. For each surgery, the dogs received an injection of amoxicillin once a day from the day before the surgery and for 7 days to prevent any infection, an oral cavity disinfection with chlorhexidine 0.2% and local anesthesia using articaine and 1:100 000 epinephrine. For pain control, the animals received 3 intravenous injections of morphine: for premedication, at the end of the procedure, and 4 hours after extubation (0.2mg/kg). A transcutaneous fentanyl patch was placed on the day of surgery (75\u0026micro;g/h). Meloxicam was given to the animals for 10 days (0.2mg/kg/d the first day and 0.1mg/kg/d the next 9 days). During the first surgery, the mandibular second, third and fourth premolars, along with the first molar were carefully extracted on both sides. After an 8-week healing period, a total of 30 implants (15 MII and 15 RI) were bilaterally and randomly placed in the mandible of each dog (Fig.\u0026nbsp;3a). However, the impossibility of taking a 3D intraoperative image, as recommended by the manufacturer, made it difficult to verify the correct bone embedding of the MII. Eight weeks after implant placement, healing abutments were connected to each implant with a small mid-crestal incision for RI. Flapless surgery was made for MII. For RI, a conventional 2-stage surgical protocol with a mucoperiosteal flap elevation and sequential drills for implant osteotomy were performed following the manufacturer\u0026rsquo;s instructions (Fig.\u0026nbsp;3b).\u003c/p\u003e\n\u003ch3\u003eClinical analysis\u003c/h3\u003e\n\u003cp\u003eThe height of keratinized tissue (mm) around the implant was clinically evaluated at 6 different probing points, and also on histological sections, after sacrificing the animals at the end of the study. Implant stability was measured using Periotest\u0026reg; (Dentisystem\u0026reg;, Bese, Hungary) at implant placement (T0), healing abutment placement (T\u0026thinsp;+\u0026thinsp;8W), and at the end of the study (T\u0026thinsp;+\u0026thinsp;16W) for the RI; this was also measured at the same time-points for MII. The Periotest\u0026reg; scale extends from \u0026minus;\u0026thinsp;8 to +\u0026thinsp;50 Periotest value (PTV); the lower the value, the greater the stability of the measured implant [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Before harvesting at T\u0026thinsp;+\u0026thinsp;16W, peri-implant inflammation was measured using a periodontal probe scored using the Carter and Barnes\u0026rsquo;s Gingival Bleeding Index (0\u0026thinsp;=\u0026thinsp;no bleeding, 1\u0026thinsp;=\u0026thinsp;bleeding) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Plaque Index was measured using the Loe and Silness\u0026rsquo;s plaque Index (0\u0026thinsp;=\u0026thinsp;no plaque in the gingival area; 1\u0026thinsp;=\u0026thinsp;presence of a film of plaque that may only be recognized by running a probe across the tooth surface; 2\u0026thinsp;=\u0026thinsp;moderate accumulation of soft deposits which can be seen by the naked eye; 3\u0026thinsp;=\u0026thinsp;abundance of plaque) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eRadiological analysis\u003c/h2\u003e \u003cp\u003eIntraoral radiographs were taken at implant placement (T0), at healing abutment placement (T\u0026thinsp;+\u0026thinsp;8W), and at the end of the study (T\u0026thinsp;+\u0026thinsp;16W). Angulators were customized (Unifast TRAD\u0026reg; resin; GC\u0026reg;, Lucerne, Switzerland) to ensure precise placement of receptors and standardize radiographs to minimize distortion and angulation errors. An image analysis program (ImageJ\u0026reg; v1.46h, National Institute of Health, Bethesda, MD, US) was used to superimpose the radiographs taken at implant placement (T0) and the end of the study (T\u0026thinsp;+\u0026thinsp;16W) to measure the peri-implant marginal remodeling. This peri-implant marginal remodeling was calculated by the difference (mm) between the distance from the apex to the \u003cem\u003ef\u003c/em\u003eBIC at the end of the study (T\u0026thinsp;+\u0026thinsp;16W) compared to implant placement (T0). There was high agreement between the 2 examiners (reliability coefficient\u0026thinsp;\u0026gt;\u0026thinsp;0.999).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSample collection and histologic preparation\u003c/h3\u003e\n\u003cp\u003eThe animals were sacrificed 4 months after implant placement with an intravenous lethal dose of pentobarbital. The samples were then collected using a trephine under profuse saline irrigation and fixed with 2% glutaraldehyde \u0026minus;\u0026thinsp;2% paraformaldehyde in a sodium cacodylate buffer for 1 week. Dehydration was performed in serial steps of increasing ethanol concentration and the blocks were finally embedded in methyl methacrylate. Non-decalcified sections were prepared using a method adapted from Donath and Breuner [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Two cuts were performed for the polymerized blocks: 1 mesio-distal and 1 bucco-lingual, parallel to the long axis of each implant using a diamond wire saw. Then, the sections were obtained and reduced by micro grinding and polishing to a thickness of about 40\u0026micro;m. These sections were then superficially stained with a modified paragon stain and digitized for histomorphometric quantification.\u003c/p\u003e\n\u003ch3\u003eHistomorphometric analysis\u003c/h3\u003e\n\u003cp\u003eThe images were analyzed by 2 different investigators (AB and CC) using ImageJ\u0026reg; (v1.46h, National Institute of Health). Before the analysis, the 2 investigators used randomly selected sessions from other animal studies for calibration. The following measurements were performed for each section and a mean was calculated on left and right side for the mesio-distal and bucco-lingual sections. The following landmarks were identified for linear measurements (\u0026micro;m): the marginal position of the peri-implant mucosa (PM); the apical termination of the pocket epithelium (aJE); the most coronal bone-to-implant contact (\u003cem\u003ef\u003c/em\u003eBIC); the top of the bone crest (BC); and the implant shoulder (IS; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe primary endpoint was the height of biological width (PM-\u003cem\u003ef\u003c/em\u003eBIC). Secondary endpoints were bone resorption/apposition (IS-BC), in sections with BC above the IS a positive value (+) was given, whereas when BC was below IS a negative value (-) was used [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], hight of epithelial tissue (PM-aJE), hight of connective tissue (aJE-\u003cem\u003ef\u003c/em\u003eBIC), the peri implant crestal bone level (IS-\u003cem\u003ef\u003c/em\u003eBIC), and marginal bone level (BC-\u003cem\u003ef\u003c/em\u003eBIC). The percentage of bone-to-implant contact (%BIC) was also calculated for each mesio-distal section; this corresponded to the percentage of the height of the bone in direct contact with the implant and the bone and the length of the total surface of the implant [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eTo compare IS-BC between the 2 implants 15 values per implant were sufficient to have 80% power to detect an effect size of 0.80; a total of 5 dogs each with 6 implants were therefore used in the present study.\u003c/p\u003e \u003cp\u003eTo evaluate the inter-examiner reliability between the 2 investigators for the histomorphometric and radiographic analysis Lin\u0026rsquo;s concordance correlation coefficient for agreement on a continuous measure was calculated (function epi.ccc of R package Epi) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Only the bias correction factor (C.b) that measures how far the best-fit line deviates from a line at 45 degrees is reported; no deviation from the 45-degree line occurs when C.b\u0026thinsp;=\u0026thinsp;1. In case of good agreement, the mean of both values was conserved in the further analyses.\u003c/p\u003e \u003cp\u003eQuantitative data were reported as mean with standard deviation (SD) and qualitative binary data as frequency with relative frequency, n (%). Ordinal data were treated as quantitative data.\u003c/p\u003e \u003cp\u003eTo compare quantitative data between implants, a linear mixed effects model was fitted with implant as explanatory variable and random intercept for dogs. Assumptions of models were checked. Fisher\u0026rsquo;s exact test was used to compare the distribution of binary data of both types of implants in clinical analysis.\u003c/p\u003e \u003cp\u003eFor all tests a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant. No adjustment was made for multiple comparisons as variables were interpreted separately regardless of time. Statistical analyses were performed using R language version 4.1.0 available at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://cran.r-project.org\u003c/span\u003e\u003cspan address=\"http://cran.r-project.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eClinical findings\u003c/h2\u003e \u003cp\u003eAll the animals survived, and all the extracted teeth healed well before implant placement. Four of the 15 implants were not osseointegrated; all 4 were MII.\u003c/p\u003e \u003cp\u003eThe mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD height of keratinized tissue around the MII significantly increased between implant placement (T0; 3.00mm\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04) and end of study (T\u0026thinsp;+\u0026thinsp;16W; 3.68mm\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and significantly decreased around the RI (3.47mm\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74 vs. 2.07mm\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e). There was no significant difference regarding bleeding and plaque indexes at the end of the study (T\u0026thinsp;+\u0026thinsp;16W; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical parameters between RI and MII group at implant placement (T0) and end of study (T\u0026thinsp;+\u0026thinsp;16W).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eKeratinized Tissue Height \u003csup\u003e+\u003c/sup\u003e(mm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT\u0026thinsp;+\u0026thinsp;16W\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e2.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e3.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGingival bleeding index, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePlaque index (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eQuantitative variables: mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD; binary variable: n (%); T: Time; W: Weeks; NA: not applicable\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eT0 vs T\u0026thinsp;+\u0026thinsp;16W: *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05; \u0026Dagger; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e+\u003c/sup\u003e Value measured clinically at T0 and histologically at T\u0026thinsp;+\u0026thinsp;16W\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBoth groups had excellent stability (from \u0026minus;\u0026thinsp;8 to 0 PTV) with no significant difference between MII and RI at implant placement (T0) and end of study (T\u0026thinsp;+\u0026thinsp;16W), but there was a significantly greater stability in the RI group at healing abutment placement (T\u0026thinsp;+\u0026thinsp;8W; mean PTV: -4.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73 vs -1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.01, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of primary stability parameter between RI and MII group at the different follow-up times.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c8\" namest=\"c3\"\u003e \u003cp\u003eTime period\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrimary stability (PTV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT\u0026thinsp;+\u0026thinsp;8W\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eT\u0026thinsp;+\u0026thinsp;16W\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-4.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-3.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.01\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e-2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;2.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eComparison of RI and MII groups at each follow-up time:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u0026dagger; P\u0026thinsp;\u0026lt;\u0026thinsp;0.01, PTV: Periotest Value; T: Time; W: Weeks.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eRadiological findings\u003c/h2\u003e \u003cp\u003ePeri-implant bone remodeling (apex-\u003cem\u003ef\u003c/em\u003eBIC) between implant placement (T0) and end of study (T\u0026thinsp;+\u0026thinsp;16W) was significantly higher around MII (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD bone level difference 2.58mm\u0026thinsp;\u0026plusmn;\u0026thinsp;1.97) than around RI (0.63mm\u0026thinsp;\u0026plusmn;\u0026thinsp;0.36, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults from radiological measurements of the peri-implant bone remodeling (Apex-\u003cem\u003ef\u003c/em\u003eBIC) at the implant placement (T0) versus at the end of the study (T\u0026thinsp;+\u0026thinsp;16W).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMII\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone remodeling (Apex-\u003cem\u003ef\u003c/em\u003eBIC) (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.97 \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (mm). \u0026Dagger; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eHistological findings\u003c/h2\u003e \u003cp\u003eInter-examiner reliability between the 2 investigators (AB and CC) was high (C.b\u0026thinsp;=\u0026thinsp;0.999).\u003c/p\u003e \u003cp\u003eSoft tissue behavior\u003c/p\u003e \u003cp\u003eFor soft tissue mesio-distal sections, the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD PM-\u003cem\u003ef\u003c/em\u003eBIC (3680.5\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;629.2 vs. 2065.5\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;395.1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and PM-aJE distances (2327.1\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;322.9 vs. 889.9\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;435.1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were significantly greater for MII than for RI. There was no significant difference in aJE-\u003cem\u003ef\u003c/em\u003eBIC between the 2 groups. For bucco-lingual sections there was no significant difference between the 2 groups in terms of PM-\u003cem\u003ef\u003c/em\u003eBIC, PM-aJE, and aJE-\u003cem\u003ef\u003c/em\u003eBIC (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHistomorphometric findings at end of study (T\u0026thinsp;+\u0026thinsp;16W).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMII\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"6\" nameend=\"c2\" namest=\"c1\" rowspan=\"7\"\u003e \u003cp\u003eMesio-\u003c/p\u003e \u003cp\u003edistal section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePM-\u003cem\u003ef\u003c/em\u003eBIC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2065.5\u0026thinsp;\u0026plusmn;\u0026thinsp;395.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3680.5\u0026thinsp;\u0026plusmn;\u0026thinsp;629.2 \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIS-BC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-283.4\u0026thinsp;\u0026plusmn;\u0026thinsp;285.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e890.4\u0026thinsp;\u0026plusmn;\u0026thinsp;759.2 \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePM-aJE (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e889.9\u0026thinsp;\u0026plusmn;\u0026thinsp;435.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2327.1\u0026thinsp;\u0026plusmn;\u0026thinsp;322.9\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eaJE-\u003cem\u003ef\u003c/em\u003eBIC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1175.8\u0026thinsp;\u0026plusmn;\u0026thinsp;358.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1353.3\u0026thinsp;\u0026plusmn;\u0026thinsp;513.3 (p\u0026thinsp;=\u0026thinsp;0.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIS-\u003cem\u003ef\u003c/em\u003eBIC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e655.2\u0026thinsp;\u0026plusmn;\u0026thinsp;276.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e802.9\u0026thinsp;\u0026plusmn;\u0026thinsp;646.2 (p\u0026thinsp;=\u0026thinsp;0.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBC-\u003cem\u003ef\u003c/em\u003eBIC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e400.3\u0026thinsp;\u0026plusmn;\u0026thinsp;162.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1692.3\u0026thinsp;\u0026plusmn;\u0026thinsp;671.4 \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBIC (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.695\u0026thinsp;\u0026plusmn;\u0026thinsp;0.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.517\u0026thinsp;\u0026plusmn;\u0026thinsp;0.251 *\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"5\" nameend=\"c2\" namest=\"c1\" rowspan=\"6\"\u003e \u003cp\u003eBucco-lingual section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePM-\u003cem\u003ef\u003c/em\u003eBIC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3064.0\u0026thinsp;\u0026plusmn;\u0026thinsp;948.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2889.6\u0026thinsp;\u0026plusmn;\u0026thinsp;989.7 (p\u0026thinsp;=\u0026thinsp;0.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIS-BC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1424.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1039.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e253.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1200.5 \u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePM-aJE (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1516.7\u0026thinsp;\u0026plusmn;\u0026thinsp;631.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1532.0\u0026thinsp;\u0026plusmn;\u0026thinsp;775.8 (p\u0026thinsp;=\u0026thinsp;0.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eaJE-\u003cem\u003ef\u003c/em\u003eBIC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1611.4\u0026thinsp;\u0026plusmn;\u0026thinsp;949.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1357.9\u0026thinsp;\u0026plusmn;\u0026thinsp;546.6 (p\u0026thinsp;=\u0026thinsp;0.46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIS-\u003cem\u003ef\u003c/em\u003eBIC (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1466.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1056.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e940.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1070.4 (p\u0026thinsp;=\u0026thinsp;0.20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBC-\u003cem\u003ef\u003c/em\u003eBIC(\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.8\u0026thinsp;\u0026plusmn;\u0026thinsp;170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e687\u0026thinsp;\u0026plusmn;\u0026thinsp;506.3 \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003en: number of samples analyzed; Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (\u0026micro;m) and comparison of MII and RI groups *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05; \u0026dagger; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; \u0026Dagger; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; negative values maybe observed for IS/BC distance as the BC point maybe located below the IS point.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eEpithelial tissue (PM-aJE), connective tissue (aJE-\u003cem\u003ef\u003c/em\u003eBIC), biological width (PM-\u003cem\u003ef\u003c/em\u003eBIC), peri implant crestal and marginal bone levels (BC-\u003cem\u003ef\u003c/em\u003eBIC, IS-\u003cem\u003ef\u003c/em\u003eBIC, and IS-BC), and the bone-implant contact (%BIC)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHard tissue behavior\u003c/p\u003e \u003cp\u003eFor bone remodeling in mesio-distal sections, the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD IS-BC distance was negative for RI (-283.4\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;285.3) and positive for MII (890.4\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;759.2), and there was a significant difference between these values (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD BC-\u003cem\u003ef\u003c/em\u003eBIC was significantly greater for MII (1692.3\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;671.4) than for RI (400.3\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;162.1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). For bone remodeling in bucco-lingual sections, the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD IS-BC distance was significantly greater for RI (1424.9\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;1039.0) than MII (253.6\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;1200.5, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e). There was a trend towards a greater mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD IS-\u003cem\u003ef\u003c/em\u003eBIC distance for RI (1466.8\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;1056.2) than MII (940.6\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;1070.4, p\u0026thinsp;=\u0026thinsp;0.20), and the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD BC-\u003cem\u003ef\u003c/em\u003eBIC distance was significantly greater in MII (687\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;506.3) than RI (41.8\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;170, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe mean %BIC was significantly greater for RI (0.695\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;0.147) than for MII (0.517\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;0.251, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe results of this \u003cem\u003ein vivo\u003c/em\u003e preclinical study indicate that hard and soft tissue behavior differed between MII and RI. These differences may be explained by the design of the implants tested, in particular the tissue behavior around the machined smooth neck of the MII.\u003c/p\u003e \u003cp\u003eRegarding hard tissue behavior, it is now well established that the absence of thread exposure, peri-implant tissue thickness, and position of the micro-gap between the collar and the prosthesis improve the stability of peri-implant tissues [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Bone quality is also pivotal; Simons \u003cem\u003eet al\u003c/em\u003e. reported that early crestal bone loss around the neck of mandibular implants was greater when the bone was cortical rather than cancellous [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. For bone level implants, platform switching and the platform-neck design reduces the risk of exposure of rough threads and the occurrence of peri-implantitis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Regarding 1-piece implants, such as the MII, the absence of a microgap limits the risk of bone resorption. In the present study, for the IS-BC we observed a negative mean value for the RI and positive mean value for the MII in mesio-distal sections. No significant difference was found when considering only the IS-\u003cem\u003ef\u003c/em\u003eBIC distance in mesio-distal sections, but the results seemed to show a lower bone resorption in bucco-lingual sections around MII. The RI were placed at the bone crest level and the machined smooth neck of MII were placed subcrestally. However, at T\u0026thinsp;+\u0026thinsp;16W an apical displacement of the crestal bone was observed around RI compared to MII (IS-BC). Consequently, the bone crest was higher around the MII and could favor a thicker biological width around MII implants, which was confirmed by the significantly greater mean values of PM-aJE and PM-\u003cem\u003ef\u003c/em\u003eBIC on mesio-distal sections. It is of note that several authors have reported that there is no significant difference in osseointegration and peri-implant bone remodeling between 2 stage and 1 stage (with flap) surgical protocols with similar placement depth [\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The observed differences in the present study could be explained by the use of a flapless technique for MII, however intraoperative 3D images that are part of the protocol, were not possible in this animal study. Consequently, the level of bone embedding of the rough surface of the MII implant could only be assessed using 2D imaging. As a result, we cannot exclude the possibility that some threads were positioned outside the bone in the vestibulo-lingual dimension, particularly in areas with narrow bone ridges. In addition, the oral intubation of the dogs made it impossible to check the existence of any occlusal contacts resulted in occlusal contact between the antagonist teeth and the MII. The differences in crestal bone remodeling between MII and RI is in accordance with that reported by Hermann \u003cem\u003eet al\u003c/em\u003e. who found significant cortical bone resorption on a smooth neck when comparing bone level and tissue level implants [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], but also with a meta-analysis that found that the marginal bone loss around rough threaded neck implants was significantly less than around the machined smooth neck in subcrestal placement [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. This was confirmed by the radiological findings herein that showed peri-implant bone remodeling (apex-\u003cem\u003ef\u003c/em\u003eBIC) between implant placement (T0) and end of study (T\u0026thinsp;+\u0026thinsp;16W) was significantly greater around MII than around RI.\u003c/p\u003e \u003cp\u003eAs described in the literature, only gingival cells can adhere to the smooth neck and the bone initially present around the collar was replaced by soft tissues [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] as found herein. The resultant larger epithelio-conjunctival attachment for MII could create a barrier to bacterial infiltration. Furthermore, the clinical results show a reduced thickness of keratinized tissue at implant placement (T0) around MII, which can be explained by the removal of keratinized tissue in the MII surgical protocol (Magic drill trephine). But after tissue maturation at T\u0026thinsp;+\u0026thinsp;16W the results are inversed, the keratinized tissue was significantly thicker around MII. This observation was confirmed by the histological results that showed a higher mean soft tissue height around MII between implant placement (T0) and end of study (T\u0026thinsp;+\u0026thinsp;16W) whereas there was a significant mean soft tissue reduction around RI. This phenomenon may indicate that a minimally invasive procedure along with a 1-piece smooth neck implant develop a sufficiently dense epithelial barrier and thick keratinized soft gingival tissue to prevent peri-implantitis [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. This hypothesis is supported by the results of an \u003cem\u003ein vitro\u003c/em\u003e study reported by Attik \u003cem\u003eet al\u003c/em\u003e. showing that adhesion and proliferation of human gingival fibroblasts are higher on the MII than on the RI under the scanning electron microscopy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, this difference may be reduced by the new smooth anodized surface at the neck of the RI (Xeal\u003csup\u003e\u0026reg;\u003c/sup\u003e surface replacing the rough TiUnit\u003csup\u003e\u0026reg;\u003c/sup\u003e surface) that allows the attachment of gingival soft tissues [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] to create a protective barrier on the underlying bone and improve long-term soft tissue stability [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor %BIC, the differences in surface treatment and thread design of RI and MII can explain the observed differences, as reported by Abrahamsson \u003cem\u003eet al\u003c/em\u003e. who found that micro-thread implants had a larger %BIC in comparison to macro-thread implants [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, the absence of significant difference in the mean bleeding index score between the 2 groups suggests that neither implant is more favorable for the development of a peri-implant inflammation. The greater frequency of Plaque Index 3 on MII can be explained by the wide MII platform design, compared to RI, which could be of importance as it is recognized that the presence of plaque leads to more bone resorption [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConcerning implant stability, the significant increase observed at healing abutment placement (T\u0026thinsp;+\u0026thinsp;8W) for RI can be explained by the difference in thread design and the implantation protocol; RI self-tapping implants obtain stability through undersized drilling and cortical bone compression in contrast with the adjusted implantation without bone compression (Magic Fin Thread) by fine morphological contact in cancellous bone of the MII. Furthermore, the study reported by Coutant \u003cem\u003eet al\u003c/em\u003e. showed that the primary stability of Magic Fin Thread was compatible with clinical osseointegration in sinus sites with severe bone atrophy (posterior maxillary areas with type IV bone and residual bone height 4 mm) [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe aim of this \u003cem\u003ein vivo\u003c/em\u003e preclinical study was to compare 2 different surgical protocols (with and without the opening of a flap) and these differed in 3 aspects (submerged versus transgingival healing, flap versus no flap, and different implant designs), which could be considered to be a limitation. We deliberately did not confine ourselves to comparing 2 different implant designs (bone level vs tissue level) or different levels of implant embedding, rather we investigated the advantages of placing an MII in terms of tissue quality, compared to a RI placed using conventional flap surgery. The comparison of identical mucosal healing between the 2 implants would only be possible if the RI implants and abutment were placed at the same time. We chose to follow the standard protocol for placing a BL implant with two surgical steps. This procedure is used clinically where RI implants can be put into function from 8 weeks according to the available data. This decision can indeed be considered as a limitation for soft tissue healing. Another limitation is the absence of 3D imaging and intubation through the mouth of the dogs, which could have influenced the results; however, unlike this animal study, clinicians who use MII will be able to verify the implant depths; furthermore, the canine model does not allow the assessment of infectious and hemorrhagic risk factors and therefore it is difficult to generalize the results to medically compromised patients. A clinical study targeted this population, respecting the MII insertion protocol and using 3D imaging, could be conducted to verify the results of the present study.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe present \u003cem\u003ein vivo\u003c/em\u003e preclinical study found a greater thickness of the epithelial-connective tissue for MII compared to RI, which contributed to the formation of a biological space that promoted physiological tissue remodeling and supported favorable tissue stability, thereby the hypothesis was accepted. It would now be interesting to confirm these results in humans, particularly in the elderly and medically compromised patients for whom the atraumatic flapless surgical protocol seems particularly suitable.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMII\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eminimally invasive implant\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ereference implant\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003efBIC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efirst Bone to Implant Contact\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eImplant Shoulder\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBone Crest\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaJE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eapical Junction Epithelial\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePeri implant Mucosa\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Union\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eARRIVE guidelines\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAnimal Research:Reporting of In Vivo Experiments\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPAFIS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAuthorization number for projects using animals for scientific purposes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eC.b\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebias correction factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard Deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of Interest:\u003c/h2\u003e \u003cp\u003eThe authors have stated explicitly that there are no conflicts of interest in connection with this study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSources of Funding Statement\u003c/strong\u003e \u003cp\u003eThis study was supported by an industrial partnership with InnoBioSurg (Daejon, Republic of Korea)\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003e All applicable international guidelines for the care and use of animals were complied with according to the Institutional Animal Care Guidelines of the French National ministry of research\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.B., B.G. and A.L. wrote the main manuscript. G.N. supervised the animal study, MPG made statistical analysis, A.L. reviewed the manuscript\u003c/p\u003e\u003ch2\u003eAcknowledgments:\u003c/h2\u003e \u003cp\u003eThe authors would like to thank Philip Robinson (DRS, Hospices Civils de Lyon) for manuscript preparation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eArısan V, B\u0026ouml;l\u0026uuml;kbaşı N, \u0026Ouml;ks\u0026uuml;z L. Computer-assisted flapless implant placement reduces the incidence of surgery-related bacteremia. Clin Oral Investig. 2013 Dec;17(9):1985\u0026ndash;93. \u003c/li\u003e\n\u003cli\u003eDudley J. Implants for the ageing population. Aust Dent J. 2015 Mar;60 Suppl 1:28\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eVissink A, Spijkervet F, Raghoebar GM. The medically compromised patient: Are dental implants a feasible option? Oral Dis. 2018 Mar;24(1\u0026ndash;2):253\u0026ndash;60. \u003c/li\u003e\n\u003cli\u003eKumar D, Sivaram G, Shivakumar B, Kumar T. Comparative evaluation of soft and hard tissue changes following endosseous implant placement using flap and flapless techniques in the posterior edentulous areas of the mandible-a randomized controlled trial. Oral Maxillofac Surg. 2018 Jun;22(2):215\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eBecker W, Goldstein M, Becker BE, Sennerby L. Minimally invasive flapless implant surgery: a prospective multicenter study. Clin Implant Dent Relat Res. 2005;7 Suppl 1:S21-27. \u003c/li\u003e\n\u003cli\u003eRomero-Ruiz MM, Mosquera-Perez R, Gutierrez-Perez JL, Torres-Lagares D. Flapless implant surgery: A review of the literature and 3 case reports. J Clin Exp Dent. 2015 Feb 1;7(1):e146\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eLlamas-Monteagudo O, Girb\u0026eacute;s-Ballester P, Vi\u0026ntilde;a-Almunia J, Pe\u0026ntilde;arrocha-Oltra D, Pe\u0026ntilde;arrocha-Diago M. Clinical parameters of implants placed in healed sites using flapped and flapless techniques: A systematic review. Med Oral Patol Oral Cir Bucal. 2017 Sep 1;22(5):e572\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eGao X, Qin S, Cai H, Wan Q. Comparison of general and aesthetic effects between flapless and flap techniques in dental implantation: a meta-analysis of randomized controlled trials. Int J Implant Dent. 2021 Oct 1;7(1):100. \u003c/li\u003e\n\u003cli\u003eFrizzera F, Calazans NNN, Pascoal CH, Martins ME, Mendon\u0026ccedil;a G. Flapless Guided Implant Surgeries Compared with Conventional Surgeries Performed by Nonexperienced Individuals: Randomized and Controlled Split-Mouth Clinical Trial. Int J Oral Maxillofac Implants. 2021 Aug;36(4):755\u0026ndash;61. \u003c/li\u003e\n\u003cli\u003eChrcanovic BR, Albrektsson T, Wennerberg A. Bone Quality and Quantity and Dental Implant Failure: A Systematic Review and Meta-analysis. Int J Prosthodont. 2017 Jun;30(3):219\u0026ndash;37. \u003c/li\u003e\n\u003cli\u003eDi Gianfilippo R, Valente NA, Toti P, Wang HL, Barone A. Influence of implant mucosal thickness on early bone loss: a systematic review with meta-analysis. J Periodontal Implant Sci. 2020 Aug;50(4):209\u0026ndash;25. \u003c/li\u003e\n\u003cli\u003eRamanauskaite A, Baseviciene N, Wang HL, T\u0026ouml;z\u0026uuml;m TF. Effect of history of periodontitis on implant success: meta-analysis and systematic review. Implant Dent. 2014 Dec;23(6):687\u0026ndash;96. \u003c/li\u003e\n\u003cli\u003eZheng Z, Ao X, Xie P, Jiang F, Chen W. The biological width around implant. J Prosthodont Res. 2021 Feb 24;65(1):11\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eDoornewaard R, Christiaens V, De Bruyn H, Jacobsson M, Cosyn J, Vervaeke S, et al. Long-Term Effect of Surface Roughness and Patients\u0026rsquo; Factors on Crestal Bone Loss at Dental Implants. A Systematic Review and Meta-Analysis. Clin Implant Dent Relat Res. 2017 Apr;19(2):372\u0026ndash;99. \u003c/li\u003e\n\u003cli\u003eRakic M, Galindo-Moreno P, Monje A, Radovanovic S, Wang HL, Cochran D, et al. How frequent does peri-implantitis occur? A systematic review and meta-analysis. Clin Oral Investig. 2018 May;22(4):1805\u0026ndash;16. \u003c/li\u003e\n\u003cli\u003eAttik N, Phantarasmy M, Abouelleil H, Chevalier C, Barraco A, Grosgogeat B, et al. Comparison of the Biological Behavior and Topographical Surface Assessment of a Minimally Invasive Dental Implant and a Standard Implant: An In Vitro Study. Materials (Basel). 2022 Oct 27;15(21):7540. \u003c/li\u003e\n\u003cli\u003eHermann JS, Jones AA, Bakaeen LG, Buser D, Schoolfield JD, Cochran DL. Influence of a machined collar on crestal bone changes around titanium implants: a histometric study in the canine mandible. J Periodontol. 2011 Sep;82(9):1329\u0026ndash;38. \u003c/li\u003e\n\u003cli\u003eLongoni S, Tinto M, Pacifico C, Sartori M, Andreano A. Effect of Peri-implant Keratinized Tissue Width on Tissue Health and Stability: Systematic Review and Meta-analysis. Int J Oral Maxillofac Implants. 2019 Dec;34(6):1307\u0026ndash;17. \u003c/li\u003e\n\u003cli\u003ePercie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020 Jul;18(7):e3000410. \u003c/li\u003e\n\u003cli\u003eOh JS, Kim SG, Lim SC, Ong JL. A comparative study of two noninvasive techniques to evaluate implant stability: Periotest and Osstell Mentor. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Apr;107(4):513\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eCarter HG, Barnes GP. The Gingival Bleeding Index. J Periodontol. 1974 Nov;45(11):801\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eL\u0026ouml;e H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol. 1967 Dec;38(6):Suppl:610-616. \u003c/li\u003e\n\u003cli\u003eDonath K, Breuner G. A method for the study of undecalcified bones and teeth with attached soft tissues. The S\u0026auml;ge-Schliff (sawing and grinding) technique. J Oral Pathol. 1982 Aug;11(4):318\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eSouza AB, Alshihri A, K\u0026auml;mmerer PW, Ara\u0026uacute;jo MG, Gallucci GO. Histological and micro-CT analysis of peri-implant soft and hard tissue healing on implants with different healing abutments configurations. Clin Oral Implants Res. 2018 Oct;29(10):1007\u0026ndash;15. \u003c/li\u003e\n\u003cli\u003eBabuska V, Moztarzadeh O, Kubikova T, Moztarzadeh A, Hrusak D, Tonar Z. Evaluating the osseointegration of nanostructured titanium implants in animal models: Current experimental methods and perspectives (Review). Biointerphases. 2016 Sep 15;11(3):030801. \u003c/li\u003e\n\u003cli\u003eLin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics. 1989 Mar;45(1):255\u0026ndash;68. \u003c/li\u003e\n\u003cli\u003eLiao JJZ, Lewis JW. A Note on Concordance Correlation Coefficient. PDA Journal of Pharmaceutical Science and Technology. 2000 Jan 1;54(1):23\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eBaixe S, Tenenbaum H, Etienne O. [Microbial contamination of the implant-abutment connections: Review of the literature]. Rev Stomatol Chir Maxillofac Chir Orale. 2016 Feb;117(1):20\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eSimons WF, De Smit M, Duyck J, Coucke W, Quirynen M. The proportion of cancellous bone as predictive factor for early marginal bone loss around implants in the posterior part of the mandible. Clin Oral Implants Res. 2015 Sep;26(9):1051\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eMacedo P, Pereira J, Vahey B, Henriques B, Benfatti C, Magini R, et al. Morse taper dental implants and platform switching: The new paradigm in oral implantology. European journal of dentistry. 2016 Mar [cited 2022 Sep 24];10(1).\u003c/li\u003e\n\u003cli\u003eSantiago JF, Batista VE de S, Verri FR, Hon\u0026oacute;rio HM, de Mello CC, Almeida DA dF, et al. Platform-switching implants and bone preservation: a systematic review and meta-analysis. Int J Oral Maxillofac Surg. 2016 Mar;45(3):332\u0026ndash;45. \u003c/li\u003e\n\u003cli\u003eChrcanovic BR, Albrektsson T, Wennerberg A. Immediately loaded non-submerged versus delayed loaded submerged dental implants: a meta-analysis. Int J Oral Maxillofac Surg. 2015 Apr;44(4):493\u0026ndash;506. \u003c/li\u003e\n\u003cli\u003eAl Amri MD. Crestal bone loss around submerged and nonsubmerged dental implants: A systematic review. J Prosthet Dent. 2016 May;115(5):564-570.e1. \u003c/li\u003e\n\u003cli\u003eMoustafa Ali RM, Alqutaibi AY, El-Din Gomaa AS, Abdallah MF. Effect of Submerged vs Nonsubmerged Implant Placement Protocols on Implant Failure and Marginal Bone Loss: A Systematic Review and Meta-Analysis. Int J Prosthodont. 2018 Feb;31(1):15\u0026ndash;22. \u003c/li\u003e\n\u003cli\u003eHermann JS, Cochran DL, Nummikoski PV, Buser D. Crestal bone changes around titanium implants. A radiographic evaluation of unloaded nonsubmerged and submerged implants in the canine mandible. J Periodontol. 1997 Nov;68(11):1117\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eHermann JS, Buser D, Schenk RK, Cochran DL. Crestal bone changes around titanium implants. A histometric evaluation of unloaded non-submerged and submerged implants in the canine mandible. J Periodontol. 2000 Sep;71(9):1412\u0026ndash;24. \u003c/li\u003e\n\u003cli\u003eHermann JS, Schoolfield JD, Schenk RK, Buser D, Cochran DL. Influence of the size of the microgap on crestal bone changes around titanium implants. A histometric evaluation of unloaded non-submerged implants in the canine mandible. J Periodontol. 2001 Oct;72(10):1372\u0026ndash;83. \u003c/li\u003e\n\u003cli\u003eZhang Q, Yue X. Marginal Bone Loss around Machined Smooth Neck Implants Compared to Rough Threaded Neck Implants: A Systematic Review and Meta-Analysis. J Prosthodont. 2021 Jun;30(5):401\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eSchwarz F, Hegewald A, Becker J. Impact of implant-abutment connection and positioning of the machined collar/microgap on crestal bone level changes: a systematic review. Clin Oral Implants Res. 2014 Apr;25(4):417\u0026ndash;25. \u003c/li\u003e\n\u003cli\u003eKoodaryan R, Hafezeqoran A. Evaluation of Implant Collar Surfaces for Marginal Bone Loss: A Systematic Review and Meta-Analysis. Biomed Res Int. 2016;2016:4987526. \u003c/li\u003e\n\u003cli\u003eBerglundh T, Lindhe J, Ericsson I, Marinello CP, Liljenberg B, Thomsen P. The soft tissue barrier at implants and teeth. Clin Oral Implants Res. 1991;2(2):81\u0026ndash;90. \u003c/li\u003e\n\u003cli\u003eCrenn MJ, Lefort L, Brazuna RP, Dubot P, Giorgi ML, Peyre P. Anodized SLM Ti6Al4V surfaces: influence of surface characteristics on NTs growth and resulted surfaces properties. J Mater Chem B. 2024 Nov 13;12(44):11502\u0026ndash;14. \u003c/li\u003e\n\u003cli\u003eSusin C, Finger Stadler A, Fiorini T, de Sousa Rabelo M, Ramos UD, Sch\u0026uuml;pbach P. Safety and efficacy of a novel anodized abutment on soft tissue healing in Yucatan mini-pigs. Clin Implant Dent Relat Res. 2019 Mar;21 Suppl 1:34\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eRompen E, Domken O, Degidi M, Pontes AEF, Piattelli A. The effect of material characteristics, of surface topography and of implant components and connections on soft tissue integration: a literature review. Clin Oral Implants Res. 2006 Oct;17 Suppl 2:55\u0026ndash;67. \u003c/li\u003e\n\u003cli\u003eAbrahamsson I, Berglundh T. Tissue characteristics at microthreaded implants: an experimental study in dogs. Clin Implant Dent Relat Res. 2006;8(3):107\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003ePranskunas M, Poskevicius L, Juodzbalys G, Kubilius R, Jimbo R. Influence of Peri-Implant Soft Tissue Condition and Plaque Accumulation on Peri-Implantitis: a Systematic Review. J Oral Maxillofac Res. 2016 Sep;7(3):e2. \u003c/li\u003e\n\u003cli\u003eMonje A, Insua Brandariz A, Wang HL. Understanding Peri-Implantitis as a Plaque-Associated and Site-Specific Entity: On the Local Predisposing Factors. J Clin Med. 2019 Feb 25;8:279. \u003c/li\u003e\n\u003cli\u003eCoutant JC, Canepa C, Naveau A, Sedarat C, Lauverjat Y, Ella B. Evaluation of thin-threaded implants primary stability in type IV bone right after maxillary sinus floor elevation: A human cadaver study. J Prosthodont. 2024 Nov 14; \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dental implants, Minimally invasive surgical procedures, Osseointegration","lastPublishedDoi":"10.21203/rs.3.rs-6674437/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6674437/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe purpose of the to test the hypothesis that the placement of a minimally invasive implant (MII) using a flapless technique provides a better quality of peri implant tissues compared to a reference implant (RI) placed with access flap in a canine model.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this \u003cem\u003ein vivo\u003c/em\u003e preclinical study 2 types of implants (MII without flap and RI with flap) were placed in both quadrants of the mandibula. Clinical, radiological, and histomorphometry measurements were performed at implant placement (T0), at healing abutment placement (T\u0026thinsp;+\u0026thinsp;8W), and at the end of the study (T\u0026thinsp;+\u0026thinsp;16W).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA significant increase in keratinized tissue thickness was observed around MII (3.00mm\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04 vs 3.68mm\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a significant decrease for RI (3.47mm\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74 vs 2.07mm\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) between T0 and T\u0026thinsp;+\u0026thinsp;16W. The biological width, in mesio-distal sections, was significantly greater around MII (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD PM-fBIC distances: 3680.5\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;629.2) than RI (2065.5\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;395.1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Bone remodeling, in mesio-distal sections, around MII (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD IS-BC 890.4\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;759.2) was higher than the implant shoulder (IS) and was significantly greater than around RI (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD IS-BC -283.4\u0026micro;m\u0026thinsp;\u0026plusmn;\u0026thinsp;285.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for which significant bone resorption was observed around RI.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe present \u003cem\u003ein vivo\u003c/em\u003e preclinical study found a greater thickness of the epithelial-connective tissue for MII compared to RI, which contributed to the formation of a biological space that promoted physiological tissue remodeling and supported favorable tissue stability; the hypothesis was therefore accepted. It would now be interesting to confirm these results in humans, particularly in the elderly and medically compromised patients for whom the atraumatic flapless surgical protocol seems particularly suitable.\u003c/p\u003e","manuscriptTitle":"In vivo preclinical study comparing the peri implant tissue of a minimally invasive implant using a flapless technique and a bone level implant using an open flap technique","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-10 15:39:13","doi":"10.21203/rs.3.rs-6674437/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"102a7edd-cc99-44cb-b4d7-ea801c0b450c","owner":[],"postedDate":"June 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T07:39:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-10 15:39:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6674437","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6674437","identity":"rs-6674437","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}