Effectiveness of dental implants indicated for early-loading protocols on peri- implant bone healing: An animal study

Effectiveness of dental implants indicated for early-loading protocols on peri- implant bone healing: An animal study | 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 Research Article Effectiveness of dental implants indicated for early-loading protocols on peri- implant bone healing: An animal study Sheng Zheng, Toru Ogawa, Masayo Nemoto, Liwei Wu, Ziqi Xie, Longshuang Hu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6937587/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 Objective Recent advancements in dental implantology focus on surface treatments that enable early loading protocols, potentially enhancing implant stability and accelerating osseointegration. This study aimed to evaluate the effects of hydrophilic surfaces on implant stability, osseointegration, and peri-implant bone healing. Method The four different types of implants, including the Straumann SLActive ® and Thomenn Inicell ® designed for early loading protocol, and the Straumann SLA ® and Thomenn SPI ® normal controls were randomly inserted into the proximal metaphysis of the tibiae of 20 New Zealand rabbits. Two implants were placed in each tibia, yielding 80 total implants. Subsequently, half of the rabbits underwent a healing period of two weeks, while the remaining half underwent a healing period of eight weeks. The implant stability quotient (ISQ) values for all the implants were measured at 0, 2, and 8 weeks to evaluate stability. In each healing period, half of the implants were subjected to removal torque testing to assess the mechanical strength of osseointegration, while the other implants underwent micro-CT, histological, and histomorphometrical assessment to evaluate the osseointegration and peri-implant bone quality and quantity, including the relative gray value (RGV), bone-to-implant contact (BIC), peri-implant bone volume/tissue volume (BV/TV). Statistical analysis was conducted using multiple Mann-Whitney U tests. Results A tendency towards higher ISQ values in the implants indicated for the early loading protocol was observed, whereas there was no significant difference in the ISQ values overall. For Straumann implants, SLActive ® demonstrated a marginally higher removal torque value than the SLA ® group at 2 weeks ( p = 0.068). Micro-CT analysis further showed that the RGV of dental implants in the early loading group (Inicell ® ) was significantly higher than that in the normal implant group (SPI ® ) at 2 weeks ( p < 0.05). Moreover, histomorphometrical analysis showed a significantly higher value of BV/TV ROI 1 in the early loading group (Inicell ® ) than the normal control group (SPI ® ) at 2 weeks ( p < 0.05). Conclusion These results, comparing SLActive® with SLA® of Straumann, and Inicell® with SPI® of Thomenn in rabbit tibia, suggest that dental implants indicated for early loading protocol may exhibit superior osseointegration and periosteogenesis, particularly during the initial healing stage. early loading hydrophilic surface osseointegration implant stability quotient value micro-CT analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Introduction The characteristics of the dental implant surface, such as topography, chemistry, mechanical, and physical properties have a decisive influence on the process of osseointegration. [ 1 – 4 ] Comparing with the smooth surface, dental implants with moderately rough surface involves combining sand-blasting and etching with acid (SLA) have a positive impact on osseointegration which has been reached a consensus in the last few decades. [ 5 ] The use of these implants has significantly decreased the early failures post implantation. Further implant surface modifications, such as improving wettability and enhancing hydrophilic properties, facilitating a faster transition from primary mechanical stability to secondary stability and accelerating the absorption of proteins on the implant surface, enabling the application of immediate loading or early loading protocols. [ 6 – 8 ] The advantage of hydrophilic implant surfaces lies in earlier osseointegration. Numerous dental implants produced by various manufacturers are available on the market, and different manufacturers have developed various techniques to achieve moderately rough and superhydrophilic surfaces. [ 9 , 10 ] Straumann (Straumann Holding AG, Switzerland) devised an implant with a SLActive® surface based on the SLA® implant, which has a hydrophilic and chemically active surface, featuring which promotes rapid protein adsorption and osteoblast attachment. [ 11 , 12 ] Thommen [Thommen Medical AG, Grenchen Switzerland] also developed an implant with a superhydrophilic surface, featuring a modified surface containing active hydroxyl ions (OH-), which increase the surface energy and enable accelerating the absorption of proteins on implant surface named Inicell®. Both hydrophilic properties are designed to promote faster osseointegration with the aim of reducing healing time, suggesting the ability of early loading protocol. [ 13 , 14 ] Despite different surface characteristics had been revealed in vitro studies, various studies have shown that the hydrophilic dental implants as Straumann SLActive® and Thommen Inicell® lead to better clinical outcomes than the hydrophobic implants, [ 15 – 18 ] especially in critical clinical situations such as low bone density and immediate loading protocols. [ 19 ] However, the benefit of these hydrophilic treatments on dental implant surface is yet to be fully explored, the precise impact of surface treatment combined with loading protocols in the initial phase post placement requires investigation in in vivo animal studies. [ 13 ] Therefore, this study aims to compare the effects of the respective hydrophilic and normal surface of titanium implants from two different manufactures in terms of implant stability and osseointegration. Through comprehensive assessment of implant stability quotient (ISQ) values, removal torque (RT) values, and peri-implant bone morphology at 2 and 8 weeks post-implantation, [ 20 , 21 ] we aim to provide clinically relevant insights that could optimize loading protocols and surface selection strategies. The findings may contribute to improving success rates and more predictable long-term outcomes in implant dentistry. 2. Materials and methods 2.1. Ethics statement The animal study protocol was approved by the Ethics Committee of Zhejiang Chinese Medical University Laboratory Animal Research Center (resolution number IACUC-20230814-08). 2.2. Implants and Groups Eighty commercially available dental implants were utilized in this study, including forty Straumann Bone Level Implants (3.3ø × 8 mm, Instiute Straumann AG, Switzerland): twenty SLActive® implants with hydrophilic surface and twenty SLA® implants with normal surface, and forty Thommen Implants (3.5ø × 8 mm, Thommen Medical AG, Switzerland): twenty SPI® ELEMENT MC INICELL® implants with hydrophilic surface and twenty SPI® ELEMENT implants with normal surface. The SLActive® and SPI® ELEMENT MC INICELL® implants (early loading groups: SLActive and Inicell) are indicated for early loading protocols, while the SLA® and SPI® ELEMENT implants (normal loading groups: SLA and SPI) are intended for normal loading protocols. 2.3. Animals and surgical procedure Twenty mature male New Zealand White rabbits, each weighing 2.5 ± 0.5 kg, were randomly assigned to two groups (n = 10 each) based on euthanization time points: 2 weeks and 8 weeks. The rabbits were housed individually, were provided food and water ad libitum, and maintained under a 12-hour light/dark cycle at room temperature. General anesthesia was induced with 2.5% isoflurane inhalation (Isoflurane USP, Halocarbon), and local anesthesia was achieved using 2% lidocaine with epinephrine (1:80,000). The medial surfaces of both hind limb tibiae were shaved and disinfected with 5% povidone-iodine. A full-thickness incision was made to expose the proximal tibial plateau. The cortices were perforated with a low rotational speed under constant cooling with saline water in accordance with the implant manufacturer’s instructions (Straumann® & Thomenn®). Two implants were placed in each tibia: the first approximately 10 mm distal to the knee joint, and the second 10 mm distal to the first. The implants were positioned using SA-310 W&H Elcomed implant unit (W&H, Burmoos, Austria) at 15rpm (Fig. 1 A and B). A total of 80 implant products were inserted into the proximal metaphysis of the tibiae of 20 New Zealand rabbits. The control and test groups were randomly allocated on the left and right sides. Cover screws were attached, and the surgical sites were closed with resorbable sutures (4 − 0 Vicryl, Ethicon). Postoperative care included intramuscular administration of penicillin (400,000 U/day) for 5 days. Rabbits were euthanized at their designated time points under isoflurane anesthesia. 2.4. Implant stability quotient test Implant stability was assessed using the Osstell system to measure the Implant Stability Quotient (ISQ) via resonance frequency analysis. ISQ values range from 1 to 100, with higher values indicating greater stability. Measurements were taken at baseline (immediately post-implantation), 2 weeks, and 8 weeks. For each implant, ISQ value was calculated as the average of values obtained from the outside-inside (OI) and medial-distal (MD) directions (Fig. 2 ). 2.5. Removal Torque test To evaluate the mechanical strength of osseointegration, removal torque testing was performed on half of the implants in each group at 2 and 8 weeks post-implantation. The tibia was secured to ensure the implant's long axis was perpendicular to the fixation base. A torque gauge (BTG90CN, Tohnichi Mfg. Co.) was fitted to the implant head, and a counterclockwise rotational load was applied until the implant rotated. The RT value was defined as the maximum rotational load recorded during this process. 2.6. Micro-computed tomography analysis The remaining rabbit tibias were extracted, the soft tissues were removed and the tibias, including the implants were scanned using micro-computed tomography (CT) before being sectioned. The micro-CT setup and procedure were based on a previous study. [ 22 ] Each sample was positioned in a water-filled plastic cylinder (29 x 57 mm) and scanned using a micro-CT system (ScanXmate-D225RSS270, Comscantecno), which was set at 200 kV and 100mA. After three-dimensional reconstruction, a sagittal slice along the axis of the tibia and dental implant was selected for analysis. The relative gray (RG) value (where water = 0 and implant = 100) was evaluated in the region of interest (ROI) of the cortical bone and trabecular bone adjacent to implant, respectively. Two rectangles (ROIs) were set as 0.4 × 0.8 mm each in the cortical bone, four squares (ROIs) were set as 0.4 × 0.4 mm each in the trabecular bone (Fig. 3 ). 2.7. Specimen preparation After micro-CT analysis, bone-implant blocks were fixed in phosphate-buffered formalin and dehydrated through a graded alcohol series. After dehydration, the samples were then embedded in polymethyl methacrylate. Embedded specimens were sectioned along the implant axis using a diamond saw (Exakt BS-300CP; Exakt Technologies). Sections were polished to a final thickness of 40 µm (Exakt MG-400CS; Exakt Technologies) and stained with Villanueva Goldner stain for histological evaluation. 2.8. Histological and histomorphometric analysis Histological and histomorphometric analyses were conducted at 100× magnification using a light microscope (Leica DM3000; Leica Laborlux). Samples were scanned with a high-sensitivity camera (Leica DFC295; Leica Laborlux) at a resolution of 1.28 µm/pixel. Digital image processing (Adobe Photoshop CS6; Adobe Systems and ImageJ, U.S. National Institutes of Health) facilitated the following analysis: 1. Bone-to-Implant Contact Percentage (BIC%): Calculated as the sum of the lengths of direct contact between bone and implant divided by the implant length (from the highest to the lowest BIC point) multiplied by 100.​ 2. Peri-Implant Bone Volume Relative to Tissue Volume (BV/TV%): Assessed within specific reference areas. Two ROIs were defined based on their distance from the implant surface: ROI1: 0-100µm from the implant surface; ROI2: 100–500µm from the implant surface (Fig. 4 ). 2.9. Statistical analysis Statistical analysis was performed using SPSS 26.0 software (IBM Company, Armonk, New York, NY, USA). Data normality and equal variance were confirmed by the Shapiro‒Wilk and Levene tests. Statistical analysis was conducted using multiple Mann-Whitney U tests. The significance level was set at p = 0.05. 3. Results 3.1. ISQ and Removal Torque test For both Straumann and Thommen implants, a tendency towards higher ISQ values was observed in the early loading groups (SLActive and Inicell) compared to their respective normal loading groups (SLA and SPI) at both 2 and 8 weeks. However, the differences in ISQ values between the early and normal loading groups were not statistically significant overall (Fig. 5 ). The RT test analysis is shown in Fig. 6 . For Straumann implants, the SLActive group had slightly higher RT values at 2 weeks compared to the SLA group, with a marginally significant difference ( p = 0.068). The RT values were nearly identical within both Straumann and Thommen implant groups at 8 weeks. 3.2. Micro-CT and Histomorphometric analysis The micro-CT and histomorphometric results are shown in Tables 1 and 2 , respectively. Micro-CT analysis showed that at 2 weeks of healing time, the RG values in the early loading group (Inicell) were significantly higher than that in the normal loading group (SPI) in the cortical area ( p < 0.05), while no significant difference was observed in the trabecular area. Although there were also no significant differences among the groups at 8 weeks in the RG values, a tendency towards higher RG values of the implants indicated for the early loading groups (SLActive and Inicell) was observed (Table 1 ). Table 1 Micro-CT Analysis (Mean ± SD) for the Thommen Implant Groups (Normal Loading vs. Early Loading) and Straumann Implant Groups (Normal Loading vs. Early Loading) Healing time Group Cortical Trabecular Group Cortical Trabecular 2 weeks SPI 21.57 ± 5.58 a 30.99 ± 3.16 SLA 27.99 ± 4.99 29.64 ± 6.68 Inicell 35.19 ± 3.88 a 31.88 ± 4.99 SLActive 27.67 ± 7.38 33.64 ± 1.54 8 weeks SPI 28.97 ± 11.37 41.21 ± 15.39 SLA 39.75 ± 4.47 43.64 ± 8.42 Inicell 29.84 ± 10.99 42.26 ± 11.50 SLActive 39.90 ± 5.56 50.04 ± 2.77 a Indicates a significant difference between the treatment and control groups. Table 2 Histomorphometric Analysis (Mean ± SD) for the Thommen Implant Groups (Normal Loading vs. Early Loading) and Straumann Implant Groups (Normal Loading vs. Early Loading) Healing time Group BIC value Bone (BV/TV) Group BIC value Bone (BV/TV) ROI1 ROI2 ROI1 ROI2 2 weeks SPI 33.60 ± 16.37 19.77 ± 3.65 a 20.64 ± 5.67 SLA 48.39 ± 14.35 22.24 ± 2.10 24.65 ± 4.09 Inicell 40.31 ± 13.64 26.45 ± 3.41 a 26.98 ± 6.67 SLActive 49.64 ± 5.16 21.83 ± 3.90 27.10 ± 3.25 8 weeks SPI 42.92 ± 17.23 41.22 ± 8.09 43.73 ± 10.53 SLA 28.34 ± 4.96 43.66 ± 10.68 58.15 ± 3.52 Inicell 54.97 ± 23.59 47.21 ± 11.01 43.79 ± 10.04 SLActive 30.28 ± 6.31 46.61 ± 11.49 58.86 ± 11.57 a Indicates a significant difference between the treatment and control groups Figure 7 shows representative central-section histological images at 2 weeks and 8 weeks for each group. Compared with the normal loading groups (SLA and SPI), the osteogenic reaction around the implants was more prominent in the early loading groups (SLActive and Inicell), the osteogenic response of peri-implant bone tended to be more visible in most cases at 8 weeks, especially in the SLActive group. The histomorphometric reslut revealed that, in the Thommen implant groups at 2 weeks, the Inicell implants were significantly higher BV/TV in ROI1 compared to the SPI implants ( p < 0.05, Table 2 ). Although there were no significant differences between groups in other histomorphometric reslut, all the parameters in the early loading groups tended to be greater than those in normal loading groups. 4. Discussion This study assessed the potential of early loading implants (SLActive and Inicell) featuring hydrophilic surfaces and conventional loading implants (SLA and SPI) with normal surfaces in terms of osseointegration. Specifically, the evaluation encompassed the mechanical strength of osseointegration as determined by ISQ and Removal Torque tests, as well as the quality and quantity of bone surrounding each implant as evaluated through micro-computed tomography (Micro-CT) and histomorphometric analyses. Previous studies have shown that the characteristics of a dental implant surface have a decisive influence on the process of osseointegration. [ 1 – 4 ] Surface modification techniques, including titanium plasma spraying, coating with hydroxyapatite, sandblasting, acid-etching, sandblasting combined with acid-etching, laser ablation, and anodization, involve creating a micro-rough titanium surface can not only affect the morphology of cells, thereby improving bone-implant contact, but also have a positive impact on osseointegration, reducing healing time. [ 10 , 15 ] With advances in technology, modifications of the surface, such as improving wettability and hydrophilic properties, which are designed to promote faster osseointegration, [ 9 , 10 ] further shorting the time needed to achieve secondary stability of the implant and accelerating absorption of proteins on the implant surface, thus enabled application of early loading protocols. [ 6 – 8 , 10 ] It is worth emphasizing that both Straumann (Straumann Holding AG, Switzerland) and Thommen (Thommen Medical AG, Switzerland) had developed implants with a superhydrophilic surface, named SLActive® and Inicell® respectively. Take the SLActive® implant as an example, the SLActive® surface differs from the SLA® surface due to its hydrophilic properties, unlike SLA® implant, SLActive® implant undergoes rinsing under protective nitrogen gas conditions, which prevents air exposure and allows storage in a sealed tube with isotonic NaCl solution. This unique process imparts SLActive® implants with higher surface energy and greater hydrophilicity than SLA® implants. [ 15 , 16 , 23 ] According to the previous study showed that the titanium dental implants do not have similar surface properties, even though they were all created using the sandblasting combined with acid-etching (SA) process. [ 24 – 25 ] Therefore, we did not perform inter-group comparisons between the Straumann and Thommen implant groups in this study due to the surface treatment, implant design (both micro-design and macro-design) differences which may potential impact on osseointegration. [ 26 ] Instead, we conducted intra-group comparisons, comparing the two types of implants within each group (SLA ® vs. SLActive ® for Straumann, and SPI ® vs. Inicell ® for Thommen) respectively, to better understand the effects of hydrophilic surface treatment and early loading on osseointegration. The differences in the Thommen and Straumann groups at 2 weeks could be attributed to these inherent implant design factors. The observation at 2 weeks of healing time showed that most of the evaluated parameters, both the SLActive and Inicell groups outperformed their counterparts, the SLActive group had slightly higher RT values compared to the SLA group, with a marginally significant difference ( p = 0.068). Moreover, significant differences were found both in the Inicell group's RG value measurements in cortical and BV/TV% assessment in ROI1,comparing to the SPI implant. Additionally, the micro-CT analysis and histomorphometric evaluation highlighted a clear advantage of hydrophilic surfaces in the cortical region, the findings aligns with the previous study of Shin et al. [ 27 ] This suggests a more favorable early bone response around the implants with hydrophilic surfaces. While, the torque variation in Inicell implants likely reflects methodological limitations in assessing early osseointegration, [ 28 ] rather than true biological differences. This finding aligns with emerging clinical trends toward reduced healing periods, [ 10 , 14 ] while maintaining the biological principles of implant integration. This study also highlights the surface energy and wettability characteristics of these modified surfaces appear to create a more favorable micro environment for early bone deposition. [ 29 , 30 ] The present study reveals that, both Straumann and Thommen implants showed a tendency for higher ISQ values in the early loading groups (SLActive and Inicell) compared to their respective normal loading groups (SLA and SPI) after 2 and 8weeks, with a more notable increase at 8 weeks. Osseointegration is vital for implant success, comprising primary stability, established through initial bone contact, and secondary stability, which develops as bone remodeling progresses during healing. Inadequate early stability can lead to micromotion and fibrous tissue formation, undermining bone-implant contact and osseointegration. [ 31 , 32 ] Our findings suggest that early loading combined with hydrophilic surface treatments may improve ISQ values by enhancing stability in the initial phase, thus promoting more effective osseointegration in the early healing phase. Overall, the present study reveals that after 8 weeks of healing time, there were no statistically significant differences in any of the measured parameters, suggesting that the early advantage may level off with longer healing times, which is in line with previous studies. [ 12 , 20 ] However, comparing the early loading groups with their corresponding normal loading groups, the SLActive implants and the Inicell implants consistently tended to show superior performance in terms of ISQ, Removal Torque (RT)values, RG values, Bone-to-Implant contact (BIC) values and BV/TV%. The results of this study suggest that early loading implants (SLActive and Inicell) with hydrophilic surface may enhance initial osseointegration and peri-implant bone formation, particularly during the critical early healing phase. Despite its reliable methodology, this study has some limitations. There are various commercial implants available in clinical practice, each featuring different surface treatments. This study focuses on four commercially available dental implants, which may not represent some other kind of hydrophilic surface treatment technologies on osseointegration. Future studies will employ more advanced surface treatment technologies for the implants to investigate their impact on osseointegration. Moreover, longer-term studies and investigations into the biological mechanisms, including the molecular pathways that are activated by hydrophilic surfaces will be conducted both in vivo and in vitro to provide more reliable clinical practice guidelines. 5. Conclusion These results, comparing SLActive and SLA implants of Straumann, as well as Inicell and SPI implants of Thommen in rabbit tibia models, suggest that dental implants indicated for early loading protocols with hydrophilic surfaces may exhibit superior osseointegration, particularly during the initial healing phase. Abbreviations ISQ Implant stability quotient OI Outside-Inside MD Medial-Distal BIC Bone-to-Implant Contact BV/TV Bone Volume Relative to Tissue Volume ROI Regions of interest RT Removal torque RGV Relative gray value Declarations Acknowledgements Not applicable. Authors’ contributions All authors contributed to the experimental design, data acquisition and analysis, and the drafting of the original manuscript. Sheng Zheng and Toru Ogawa further led the writing, review, and editing processes, while Hiroyasu Kanetaka supervised the entire study. All authors have read and approved the final version of the manuscript. Funding This work was supported by the Pharmaceuticals and Medical Devices Regulatory Harmonization and Evaluation Research Project of the Japan Agency for Medical Research and Development (AMED). Ethics approval and consent to participate All procedures were performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Zhejiang Chinese Medical University Laboratory Animal Research Center (resolution number IACUC-20230814-08) Consent for publication Not applicable. Competing interests All authors declare that they have no competing interests. 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Impact of a hydrophilic dental implant surface on osseointegration: biomechanical results in rabbit. J Oral Implantol. 2021;47(2):163–8. Fraser D, Funkenbusch P, Ercoli C, Meirelles L. Biomechanical analysis of the osseointegration of porous tantalum implants. J Prosthet Dent. 2020;123(6):811–20. Leles CR, de Paula MS, Curado TFF, Silva JR, Leles JLR, McKenna G, Schimmel M. Flapped versus flapless surgery and delayed versus immediate loading for a four mini implant mandibular overdenture: A RCT on post-surgical symptoms and short-term clinical outcomes. Clin Oral Implants Res. 2022;33(9):953–64. 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-6937587","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":495648521,"identity":"68398436-97af-464f-8004-c9c8f9b70c09","order_by":0,"name":"Sheng Zheng","email":"","orcid":"","institution":"Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Sheng","middleName":"","lastName":"Zheng","suffix":""},{"id":495648526,"identity":"5e6b48b4-e8fe-4e61-b00f-a86733b4e34a","order_by":1,"name":"Toru Ogawa","email":"","orcid":"","institution":"Tohoku University","correspondingAuthor":false,"prefix":"","firstName":"Toru","middleName":"","lastName":"Ogawa","suffix":""},{"id":495648529,"identity":"d44a20d7-a257-47f6-b879-f25be97f7cf6","order_by":2,"name":"Masayo Nemoto","email":"","orcid":"","institution":"Tohoku University","correspondingAuthor":false,"prefix":"","firstName":"Masayo","middleName":"","lastName":"Nemoto","suffix":""},{"id":495648530,"identity":"3f7ff46e-5797-47f2-9d58-ec7c149ef360","order_by":3,"name":"Liwei Wu","email":"","orcid":"","institution":"Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Liwei","middleName":"","lastName":"Wu","suffix":""},{"id":495648532,"identity":"0bb909f7-a9f7-4abe-9675-bf316c32d917","order_by":4,"name":"Ziqi Xie","email":"","orcid":"","institution":"Tohoku University","correspondingAuthor":false,"prefix":"","firstName":"Ziqi","middleName":"","lastName":"Xie","suffix":""},{"id":495648535,"identity":"c7f695de-ae07-4396-9957-84eadbdf858f","order_by":5,"name":"Longshuang Hu","email":"","orcid":"","institution":"Tohoku University","correspondingAuthor":false,"prefix":"","firstName":"Longshuang","middleName":"","lastName":"Hu","suffix":""},{"id":495648538,"identity":"fe1f7437-dcdd-40fe-81f0-f4da275711fe","order_by":6,"name":"Kenta Shobara","email":"","orcid":"","institution":"Tohoku University","correspondingAuthor":false,"prefix":"","firstName":"Kenta","middleName":"","lastName":"Shobara","suffix":""},{"id":495648540,"identity":"01847df1-c948-4942-a061-911926fafbe6","order_by":7,"name":"Hiroki Hihara","email":"","orcid":"","institution":"Tohoku University","correspondingAuthor":false,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Hihara","suffix":""},{"id":495648543,"identity":"5df1cc30-1f47-4e20-b35b-05260fa1498c","order_by":8,"name":"Hiroyasu Kanetaka","email":"data:image/png;base64,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","orcid":"","institution":"Tohoku University","correspondingAuthor":true,"prefix":"","firstName":"Hiroyasu","middleName":"","lastName":"Kanetaka","suffix":""}],"badges":[],"createdAt":"2025-06-20 09:38:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6937587/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6937587/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88532916,"identity":"b526854f-2247-4280-9c72-122c4098aa5f","added_by":"auto","created_at":"2025-08-07 11:59:00","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":514115,"visible":true,"origin":"","legend":"\u003cp\u003eThe tibial of a rabbit after installation of two dental implants.\u003c/p\u003e\n\u003cp\u003eA: Two implants with different surfaces were inserted in each tibia,the first approximately 10 mm distal to the knee joint, the second 10 mm distal to the first; B: The process of implantation surgery.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6937587/v1/9ff3c4e71a6f0baec8b31f55.jpeg"},{"id":88533420,"identity":"f3697572-16c1-4eba-bc97-076f480c9644","added_by":"auto","created_at":"2025-08-07 12:07:00","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":212653,"visible":true,"origin":"","legend":"\u003cp\u003eThe green arrow indicates the measurement of OI (outside-inside direction) ISQ values, while the yellow arrow indicates the measurement of MD (medial-distal direction) ISQ values.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6937587/v1/d59c95856b123ee87c57c4cd.jpeg"},{"id":88532923,"identity":"e03fd9be-60df-4686-b397-59840bebde09","added_by":"auto","created_at":"2025-08-07 11:59:00","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":120499,"visible":true,"origin":"","legend":"\u003cp\u003eThe Micro-CT images illustrate the division of each implant into adjacent cortical bone and trabecular bone areas for analysis. Two observation regions were defined in the upper area of the implant, each measuring a 400×800 μm rectangle in the cortical bone adjacent to the implant. Four observation regions were defined in the lower area of the implant, each measuring a 400×400 μm square in the trabecular bone adjacent to the implant. The average data represents the relative gray value in both the cortical and trabecular bone regions surrounding the implant.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6937587/v1/25066253baa7db3bf20beb56.jpeg"},{"id":88533419,"identity":"dbfee6cf-ec2f-439f-a16b-5bd0ca35702a","added_by":"auto","created_at":"2025-08-07 12:07:00","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":268415,"visible":true,"origin":"","legend":"\u003cp\u003eThe reference sites for bone volume relative to tissue volume (BV/TV) evaluation. ROI1: 0-100 μm from the implant surface, ROI2: 100-500 μm. from the implant surface.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6937587/v1/80b3cd499bb0a302157277df.jpeg"},{"id":88532921,"identity":"cb30dd8f-bd65-43ab-8f0b-92f2c54c19d3","added_by":"auto","created_at":"2025-08-07 11:59:00","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":179930,"visible":true,"origin":"","legend":"\u003cp\u003eISQ Values (Mean ± SD) for the Thommen Implant Groups (Normal vs. Early Loading) in (A) outside–inside directions and (B) medial–distal directions, and for the Straumann Implant Groups (Normal vs. Early Loading) in (C) outside–inside directions and (D) medial–distal directions.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6937587/v1/133704c68351fdda4cd46f2c.jpeg"},{"id":88533421,"identity":"c9b7b146-811d-48cd-ad61-0d44ffca732c","added_by":"auto","created_at":"2025-08-07 12:07:00","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":95546,"visible":true,"origin":"","legend":"\u003cp\u003eRT Values (Mean ± SD) for the Straumann Implant Groups (Normal vs. Early Loading) at 2 weeks and 8 weeks in (A), and Thommen Implant Groups for the (Normal vs. Early Loading) in (B).\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6937587/v1/4442c6fec2f49dd64535b6b9.jpeg"},{"id":88532922,"identity":"3e19e9d4-063d-43db-a456-4b3c6c770ad3","added_by":"auto","created_at":"2025-08-07 11:59:00","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1020663,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative central-section histological images at 2 weeks and 8 weeks for each group.\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6937587/v1/04b9f0c64a810c84d54104ec.jpeg"},{"id":88850965,"identity":"8baafcbb-d283-4a35-9d8c-27479fd3c836","added_by":"auto","created_at":"2025-08-12 05:32:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3223697,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6937587/v1/c7c1732f-dd8c-435a-8d21-082765680128.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effectiveness of dental implants indicated for early-loading protocols on peri- implant bone healing: An animal study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe characteristics of the dental implant surface, such as topography, chemistry, mechanical, and physical properties have a decisive influence on the process of osseointegration.\u003csup\u003e[\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e Comparing with the smooth surface, dental implants with moderately rough surface involves combining sand-blasting and etching with acid (SLA) have a positive impact on osseointegration which has been reached a consensus in the last few decades.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e The use of these implants has significantly decreased the early failures post implantation.\u003c/p\u003e\u003cp\u003eFurther implant surface modifications, such as improving wettability and enhancing hydrophilic properties, facilitating a faster transition from primary mechanical stability to secondary stability and accelerating the absorption of proteins on the implant surface, enabling the application of immediate loading or early loading protocols.\u003csup\u003e[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e The advantage of hydrophilic implant surfaces lies in earlier osseointegration.\u003c/p\u003e\u003cp\u003eNumerous dental implants produced by various manufacturers are available on the market, and different manufacturers have developed various techniques to achieve moderately rough and superhydrophilic surfaces.\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e Straumann (Straumann Holding AG, Switzerland) devised an implant with a SLActive\u0026reg; surface based on the SLA\u0026reg; implant, which has a hydrophilic and chemically active surface, featuring which promotes rapid protein adsorption and osteoblast attachment.\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e Thommen [Thommen Medical AG, Grenchen Switzerland] also developed an implant with a superhydrophilic surface, featuring a modified surface containing active hydroxyl ions (OH-), which increase the surface energy and enable accelerating the absorption of proteins on implant surface named Inicell\u0026reg;. Both hydrophilic properties are designed to promote faster osseointegration with the aim of reducing healing time, suggesting the ability of early loading protocol.\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eDespite different surface characteristics had been revealed in vitro studies, various studies have shown that the hydrophilic dental implants as Straumann SLActive\u0026reg; and Thommen Inicell\u0026reg; lead to better clinical outcomes than the hydrophobic implants,\u003csup\u003e[\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e especially in critical clinical situations such as low bone density and immediate loading protocols.\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eHowever, the benefit of these hydrophilic treatments on dental implant surface is yet to be fully explored, the precise impact of surface treatment combined with loading protocols in the initial phase post placement requires investigation in in vivo animal studies.\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e Therefore, this study aims to compare the effects of the respective hydrophilic and normal surface of titanium implants from two different manufactures in terms of implant stability and osseointegration. Through comprehensive assessment of implant stability quotient (ISQ) values, removal torque (RT) values, and peri-implant bone morphology at 2 and 8 weeks post-implantation,\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e we aim to provide clinically relevant insights that could optimize loading protocols and surface selection strategies. The findings may contribute to improving success rates and more predictable long-term outcomes in implant dentistry.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Ethics statement\u003c/h2\u003e\u003cp\u003eThe animal study protocol was approved by the Ethics Committee of Zhejiang Chinese Medical University Laboratory Animal Research Center (resolution number IACUC-20230814-08).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Implants and Groups\u003c/h2\u003e\u003cp\u003eEighty commercially available dental implants were utilized in this study, including forty Straumann Bone Level Implants (3.3\u0026oslash; \u0026times; 8 mm, Instiute Straumann AG, Switzerland): twenty SLActive\u0026reg; implants with hydrophilic surface and twenty SLA\u0026reg; implants with normal surface, and forty Thommen Implants (3.5\u0026oslash; \u0026times; 8 mm, Thommen Medical AG, Switzerland): twenty SPI\u0026reg; ELEMENT MC INICELL\u0026reg; implants with hydrophilic surface and twenty SPI\u0026reg; ELEMENT implants with normal surface.\u003c/p\u003e\u003cp\u003eThe SLActive\u0026reg; and SPI\u0026reg; ELEMENT MC INICELL\u0026reg; implants (early loading groups: SLActive and Inicell) are indicated for early loading protocols, while the SLA\u0026reg; and SPI\u0026reg; ELEMENT implants (normal loading groups: SLA and SPI) are intended for normal loading protocols.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Animals and surgical procedure\u003c/h2\u003e\u003cp\u003eTwenty mature male New Zealand White rabbits, each weighing 2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 kg, were randomly assigned to two groups (n\u0026thinsp;=\u0026thinsp;10 each) based on euthanization time points: 2 weeks and 8 weeks. The rabbits were housed individually, were provided food and water ad libitum, and maintained under a 12-hour light/dark cycle at room temperature.\u003c/p\u003e\u003cp\u003eGeneral anesthesia was induced with 2.5% isoflurane inhalation (Isoflurane USP, Halocarbon), and local anesthesia was achieved using 2% lidocaine with epinephrine (1:80,000). The medial surfaces of both hind limb tibiae were shaved and disinfected with 5% povidone-iodine. A full-thickness incision was made to expose the proximal tibial plateau. The cortices were perforated with a low rotational speed under constant cooling with saline water in accordance with the implant manufacturer\u0026rsquo;s instructions (Straumann\u0026reg; \u0026amp; Thomenn\u0026reg;). Two implants were placed in each tibia: the first approximately 10 mm distal to the knee joint, and the second 10 mm distal to the first. The implants were positioned using SA-310 W\u0026amp;H Elcomed implant unit (W\u0026amp;H, Burmoos, Austria) at 15rpm (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and B). A total of 80 implant products were inserted into the proximal metaphysis of the tibiae of 20 New Zealand rabbits. The control and test groups were randomly allocated on the left and right sides. Cover screws were attached, and the surgical sites were closed with resorbable sutures (4\u0026thinsp;\u0026minus;\u0026thinsp;0 Vicryl, Ethicon). Postoperative care included intramuscular administration of penicillin (400,000 U/day) for 5 days. Rabbits were euthanized at their designated time points under isoflurane anesthesia.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Implant stability quotient test\u003c/h2\u003e\u003cp\u003eImplant stability was assessed using the Osstell system to measure the Implant Stability Quotient (ISQ) via resonance frequency analysis. ISQ values range from 1 to 100, with higher values indicating greater stability. Measurements were taken at baseline (immediately post-implantation), 2 weeks, and 8 weeks. For each implant, ISQ value was calculated as the average of values obtained from the outside-inside (OI) and medial-distal (MD) directions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5. Removal Torque test\u003c/h2\u003e\u003cp\u003eTo evaluate the mechanical strength of osseointegration, removal torque testing was performed on half of the implants in each group at 2 and 8 weeks post-implantation. The tibia was secured to ensure the implant's long axis was perpendicular to the fixation base. A torque gauge (BTG90CN, Tohnichi Mfg. Co.) was fitted to the implant head, and a counterclockwise rotational load was applied until the implant rotated. The RT value was defined as the maximum rotational load recorded during this process.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6. Micro-computed tomography analysis\u003c/h2\u003e\u003cp\u003eThe remaining rabbit tibias were extracted, the soft tissues were removed and the tibias, including the implants were scanned using micro-computed tomography (CT) before being sectioned. The micro-CT setup and procedure were based on a previous study.\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e Each sample was positioned in a water-filled plastic cylinder (29 x 57 mm) and scanned using a micro-CT system (ScanXmate-D225RSS270, Comscantecno), which was set at 200 kV and 100mA. After three-dimensional reconstruction, a sagittal slice along the axis of the tibia and dental implant was selected for analysis. The relative gray (RG) value (where water\u0026thinsp;=\u0026thinsp;0 and implant\u0026thinsp;=\u0026thinsp;100) was evaluated in the region of interest (ROI) of the cortical bone and trabecular bone adjacent to implant, respectively. Two rectangles (ROIs) were set as 0.4 \u0026times; 0.8 mm each in the cortical bone, four squares (ROIs) were set as 0.4 \u0026times; 0.4 mm each in the trabecular bone (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e2.7. Specimen preparation\u003c/h2\u003e\u003cp\u003eAfter micro-CT analysis, bone-implant blocks were fixed in phosphate-buffered formalin and dehydrated through a graded alcohol series. After dehydration, the samples were then embedded in polymethyl methacrylate. Embedded specimens were sectioned along the implant axis using a diamond saw (Exakt BS-300CP; Exakt Technologies). Sections were polished to a final thickness of 40 \u0026micro;m (Exakt MG-400CS; Exakt Technologies) and stained with Villanueva Goldner stain for histological evaluation.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e2.8. Histological and histomorphometric analysis\u003c/h2\u003e\u003cp\u003eHistological and histomorphometric analyses were conducted at 100\u0026times; magnification using a light microscope (Leica DM3000; Leica Laborlux). Samples were scanned with a high-sensitivity camera (Leica DFC295; Leica Laborlux) at a resolution of 1.28 \u0026micro;m/pixel. Digital image processing (Adobe Photoshop CS6; Adobe Systems and ImageJ, U.S. National Institutes of Health) facilitated the following analysis:\u003c/p\u003e\u003cp\u003e1. Bone-to-Implant Contact Percentage (BIC%): Calculated as the sum of the lengths of direct contact between bone and implant divided by the implant length (from the highest to the lowest BIC point) multiplied by 100.​\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003e2. Peri-Implant Bone Volume Relative to Tissue Volume (BV/TV%): Assessed within specific reference areas.\u003c/h3\u003e\n\u003cp\u003eTwo ROIs were defined based on their distance from the implant surface: ROI1: 0-100\u0026micro;m from the implant surface; ROI2: 100\u0026ndash;500\u0026micro;m from the implant surface (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e2.9. Statistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS 26.0 software (IBM Company, Armonk, New York, NY, USA). Data normality and equal variance were confirmed by the Shapiro‒Wilk and Levene tests. Statistical analysis was conducted using multiple Mann-Whitney U tests. The significance level was set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.1. ISQ and Removal Torque test\u003c/h2\u003e\u003cp\u003eFor both Straumann and Thommen implants, a tendency towards higher ISQ values was observed in the early loading groups (SLActive and Inicell) compared to their respective normal loading groups (SLA and SPI) at both 2 and 8 weeks. However, the differences in ISQ values between the early and normal loading groups were not statistically significant overall (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe RT test analysis is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. For Straumann implants, the SLActive group had slightly higher RT values at 2 weeks compared to the SLA group, with a marginally significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.068). The RT values were nearly identical within both Straumann and Thommen implant groups at 8 weeks.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Micro-CT and Histomorphometric analysis\u003c/h2\u003e\u003cp\u003eThe micro-CT and histomorphometric results are shown in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, respectively. Micro-CT analysis showed that at 2 weeks of healing time, the RG values in the early loading group (Inicell) were significantly higher than that in the normal loading group (SPI) in the cortical area (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while no significant difference was observed in the trabecular area. Although there were also no significant differences among the groups at 8 weeks in the RG values, a tendency towards higher RG values of the implants indicated for the early loading groups (SLActive and Inicell) was observed (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\u003eMicro-CT Analysis (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) for the Thommen Implant Groups (Normal Loading vs. Early Loading) and Straumann Implant Groups (Normal Loading vs. Early Loading)\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=\"char\" char=\"\u0026plusmn;\" 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\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHealing time\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCortical\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTrabecular\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCortical\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eTrabecular\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSPI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.57\u0026thinsp;\u0026plusmn;\u0026thinsp;5.58\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e30.99\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSLA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e27.99\u0026thinsp;\u0026plusmn;\u0026thinsp;4.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e29.64\u0026thinsp;\u0026plusmn;\u0026thinsp;6.68\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInicell\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35.19\u0026thinsp;\u0026plusmn;\u0026thinsp;3.88\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e31.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSLActive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e27.67\u0026thinsp;\u0026plusmn;\u0026thinsp;7.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e33.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e8 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSPI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.97\u0026thinsp;\u0026plusmn;\u0026thinsp;11.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e41.21\u0026thinsp;\u0026plusmn;\u0026thinsp;15.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSLA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e39.75\u0026thinsp;\u0026plusmn;\u0026thinsp;4.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e43.64\u0026thinsp;\u0026plusmn;\u0026thinsp;8.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInicell\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.84\u0026thinsp;\u0026plusmn;\u0026thinsp;10.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e42.26\u0026thinsp;\u0026plusmn;\u0026thinsp;11.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSLActive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e39.90\u0026thinsp;\u0026plusmn;\u0026thinsp;5.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e\u003cp\u003e50.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003ea\u003c/sup\u003e Indicates a significant difference between the treatment and control groups.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\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\u003eHistomorphometric Analysis (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) for the Thommen Implant Groups (Normal Loading vs. Early Loading) and Straumann Implant Groups (Normal Loading vs. Early Loading)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\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=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHealing time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBIC value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eBone (BV/TV)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBIC value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003eBone (BV/TV)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eROI1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eROI2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eROI1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eROI2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSPI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.60\u0026thinsp;\u0026plusmn;\u0026thinsp;16.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.77\u0026thinsp;\u0026plusmn;\u0026thinsp;3.65\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSLA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e48.39\u0026thinsp;\u0026plusmn;\u0026thinsp;14.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e22.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e24.65\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInicell\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40.31\u0026thinsp;\u0026plusmn;\u0026thinsp;13.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.45\u0026thinsp;\u0026plusmn;\u0026thinsp;3.41\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e26.98\u0026thinsp;\u0026plusmn;\u0026thinsp;6.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSLActive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e49.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e21.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e27.10\u0026thinsp;\u0026plusmn;\u0026thinsp;3.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e8 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSPI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42.92\u0026thinsp;\u0026plusmn;\u0026thinsp;17.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41.22\u0026thinsp;\u0026plusmn;\u0026thinsp;8.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e43.73\u0026thinsp;\u0026plusmn;\u0026thinsp;10.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSLA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e28.34\u0026thinsp;\u0026plusmn;\u0026thinsp;4.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e43.66\u0026thinsp;\u0026plusmn;\u0026thinsp;10.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e58.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInicell\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54.97\u0026thinsp;\u0026plusmn;\u0026thinsp;23.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e47.21\u0026thinsp;\u0026plusmn;\u0026thinsp;11.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e43.79\u0026thinsp;\u0026plusmn;\u0026thinsp;10.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSLActive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e30.28\u0026thinsp;\u0026plusmn;\u0026thinsp;6.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e46.61\u0026thinsp;\u0026plusmn;\u0026thinsp;11.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e58.86\u0026thinsp;\u0026plusmn;\u0026thinsp;11.57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csup\u003ea\u003c/sup\u003e Indicates a significant difference between the treatment and control groups\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e shows representative central-section histological images at 2 weeks and 8 weeks for each group. Compared with the normal loading groups (SLA and SPI), the osteogenic reaction around the implants was more prominent in the early loading groups (SLActive and Inicell), the osteogenic response of peri-implant bone tended to be more visible in most cases at 8 weeks, especially in the SLActive group. The histomorphometric reslut revealed that, in the Thommen implant groups at 2 weeks, the Inicell implants were significantly higher BV/TV in ROI1 compared to the SPI implants (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Although there were no significant differences between groups in other histomorphometric reslut, all the parameters in the early loading groups tended to be greater than those in normal loading groups.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study assessed the potential of early loading implants (SLActive and Inicell) featuring hydrophilic surfaces and conventional loading implants (SLA and SPI) with normal surfaces in terms of osseointegration. Specifically, the evaluation encompassed the mechanical strength of osseointegration as determined by ISQ and Removal Torque tests, as well as the quality and quantity of bone surrounding each implant as evaluated through micro-computed tomography (Micro-CT) and histomorphometric analyses.\u003c/p\u003e\u003cp\u003ePrevious studies have shown that the characteristics of a dental implant surface have a decisive influence on the process of osseointegration.\u003csup\u003e[\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e Surface modification techniques, including titanium plasma spraying, coating with hydroxyapatite, sandblasting, acid-etching, sandblasting combined with acid-etching, laser ablation, and anodization, involve creating a micro-rough titanium surface can not only affect the morphology of cells, thereby improving bone-implant contact, but also have a positive impact on osseointegration, reducing healing time.\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWith advances in technology, modifications of the surface, such as improving wettability and hydrophilic properties, which are designed to promote faster osseointegration,\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e further shorting the time needed to achieve secondary stability of the implant and accelerating absorption of proteins on the implant surface, thus enabled application of early loading protocols.\u003csup\u003e[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e It is worth emphasizing that both Straumann (Straumann Holding AG, Switzerland) and Thommen (Thommen Medical AG, Switzerland) had developed implants with a superhydrophilic surface, named SLActive\u0026reg; and Inicell\u0026reg; respectively. Take the SLActive\u0026reg; implant as an example, the SLActive\u0026reg; surface differs from the SLA\u0026reg; surface due to its hydrophilic properties, unlike SLA\u0026reg; implant, SLActive\u0026reg; implant undergoes rinsing under protective nitrogen gas conditions, which prevents air exposure and allows storage in a sealed tube with isotonic NaCl solution. This unique process imparts SLActive\u0026reg; implants with higher surface energy and greater hydrophilicity than SLA\u0026reg; implants.\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAccording to the previous study showed that the titanium dental implants do not have similar surface properties, even though they were all created using the sandblasting combined with acid-etching (SA) process.\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e Therefore, we did not perform inter-group comparisons between the Straumann and Thommen implant groups in this study due to the surface treatment, implant design (both micro-design and macro-design) differences which may potential impact on osseointegration.\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e Instead, we conducted intra-group comparisons, comparing the two types of implants within each group (SLA\u003csup\u003e\u0026reg;\u003c/sup\u003e vs. SLActive\u003csup\u003e\u0026reg;\u003c/sup\u003e for Straumann, and SPI\u003csup\u003e\u0026reg;\u003c/sup\u003e vs. Inicell\u003csup\u003e\u0026reg;\u003c/sup\u003e for Thommen) respectively, to better understand the effects of hydrophilic surface treatment and early loading on osseointegration. The differences in the Thommen and Straumann groups at 2 weeks could be attributed to these inherent implant design factors.\u003c/p\u003e\u003cp\u003eThe observation at 2 weeks of healing time showed that most of the evaluated parameters, both the SLActive and Inicell groups outperformed their counterparts, the SLActive group had slightly higher RT values compared to the SLA group, with a marginally significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.068). Moreover, significant differences were found both in the Inicell group's RG value measurements in cortical and BV/TV% assessment in ROI1,comparing to the SPI implant. Additionally, the micro-CT analysis and histomorphometric evaluation highlighted a clear advantage of hydrophilic surfaces in the cortical region, the findings aligns with the previous study of Shin et al.\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e This suggests a more favorable early bone response around the implants with hydrophilic surfaces. While, the torque variation in Inicell implants likely reflects methodological limitations in assessing early osseointegration,\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e rather than true biological differences. This finding aligns with emerging clinical trends toward reduced healing periods,\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e while maintaining the biological principles of implant integration. This study also highlights the surface energy and wettability characteristics of these modified surfaces appear to create a more favorable micro environment for early bone deposition.\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe present study reveals that, both Straumann and Thommen implants showed a tendency for higher ISQ values in the early loading groups (SLActive and Inicell) compared to their respective normal loading groups (SLA and SPI) after 2 and 8weeks, with a more notable increase at 8 weeks. Osseointegration is vital for implant success, comprising primary stability, established through initial bone contact, and secondary stability, which develops as bone remodeling progresses during healing. Inadequate early stability can lead to micromotion and fibrous tissue formation, undermining bone-implant contact and osseointegration.\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e Our findings suggest that early loading combined with hydrophilic surface treatments may improve ISQ values by enhancing stability in the initial phase, thus promoting more effective osseointegration in the early healing phase.\u003c/p\u003e\u003cp\u003eOverall, the present study reveals that after 8 weeks of healing time, there were no statistically significant differences in any of the measured parameters, suggesting that the early advantage may level off with longer healing times, which is in line with previous studies.\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e However, comparing the early loading groups with their corresponding normal loading groups, the SLActive implants and the Inicell implants consistently tended to show superior performance in terms of ISQ, Removal Torque (RT)values, RG values, Bone-to-Implant contact (BIC) values and BV/TV%. The results of this study suggest that early loading implants (SLActive and Inicell) with hydrophilic surface may enhance initial osseointegration and peri-implant bone formation, particularly during the critical early healing phase.\u003c/p\u003e\u003cp\u003eDespite its reliable methodology, this study has some limitations. There are various commercial implants available in clinical practice, each featuring different surface treatments. This study focuses on four commercially available dental implants, which may not represent some other kind of hydrophilic surface treatment technologies on osseointegration. Future studies will employ more advanced surface treatment technologies for the implants to investigate their impact on osseointegration. Moreover, longer-term studies and investigations into the biological mechanisms, including the molecular pathways that are activated by hydrophilic surfaces will be conducted both in vivo and in vitro to provide more reliable clinical practice guidelines.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThese results, comparing SLActive and SLA implants of Straumann, as well as Inicell and SPI implants of Thommen in rabbit tibia models, suggest that dental implants indicated for early loading protocols with hydrophilic surfaces may exhibit superior osseointegration, particularly during the initial healing phase.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eISQ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eImplant stability quotient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOutside-Inside\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedial-Distal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBIC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBone-to-Implant Contact\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBV/TV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBone Volume Relative to Tissue Volume\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eROI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRegions of interest\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRemoval torque\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRGV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRelative gray value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the experimental design, data acquisition and analysis, and the drafting of the original manuscript. Sheng Zheng and Toru Ogawa further led the writing, review, and editing processes, while Hiroyasu Kanetaka supervised the entire study. All authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Pharmaceuticals and Medical Devices Regulatory Harmonization and Evaluation Research Project of the Japan Agency for Medical Research and Development (AMED).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures were performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Zhejiang Chinese Medical University Laboratory Animal Research Center (resolution number IACUC-20230814-08)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets supporting the conclusions of this article are included within the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlbrektsson T, Wennerberg A. 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Int J Mol Sci. 2021;22(17):9361.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShobara K, Ogawa T, Shibamoto A, Miyashita M, Ito A, Sitalaksmi RM. Osteogenic effect of low-intensity pulsed ultrasound and whole‐body vibration on peri‐implant bone. An experimental in vivo study. Clin Oral Implants Res. 2021;32(5):641\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJinno Y, Stocchero M, Galli S, Toia M, Becktor JP. Impact of a hydrophilic dental implant surface on osseointegration: biomechanical results in rabbit. J Oral Implantol. 2021;47(2):163\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFraser D, Funkenbusch P, Ercoli C, Meirelles L. Biomechanical analysis of the osseointegration of porous tantalum implants. J Prosthet Dent. 2020;123(6):811\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLeles CR, de Paula MS, Curado TFF, Silva JR, Leles JLR, McKenna G, Schimmel M. Flapped versus flapless surgery and delayed versus immediate loading for a four mini implant mandibular overdenture: A RCT on post-surgical symptoms and short-term clinical outcomes. Clin Oral Implants Res. 2022;33(9):953\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\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":"early loading, hydrophilic surface, osseointegration, implant stability quotient value, micro-CT analysis","lastPublishedDoi":"10.21203/rs.3.rs-6937587/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6937587/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eRecent advancements in dental implantology focus on surface treatments that enable early loading protocols, potentially enhancing implant stability and accelerating osseointegration. This study aimed to evaluate the effects of hydrophilic surfaces on implant stability, osseointegration, and peri-implant bone healing.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003eThe four different types of implants, including the Straumann SLActive\u003csup\u003e\u0026reg;\u003c/sup\u003e and Thomenn Inicell\u003csup\u003e\u0026reg;\u003c/sup\u003e designed for early loading protocol, and the Straumann SLA\u003csup\u003e\u0026reg;\u003c/sup\u003e and Thomenn SPI\u003csup\u003e\u0026reg;\u003c/sup\u003e normal controls were randomly inserted into the proximal metaphysis of the tibiae of 20 New Zealand rabbits. Two implants were placed in each tibia, yielding 80 total implants. Subsequently, half of the rabbits underwent a healing period of two weeks, while the remaining half underwent a healing period of eight weeks. The implant stability quotient (ISQ) values for all the implants were measured at 0, 2, and 8 weeks to evaluate stability. In each healing period, half of the implants were subjected to removal torque testing to assess the mechanical strength of osseointegration, while the other implants underwent micro-CT, histological, and histomorphometrical assessment to evaluate the osseointegration and peri-implant bone quality and quantity, including the relative gray value (RGV), bone-to-implant contact (BIC), peri-implant bone volume/tissue volume (BV/TV). Statistical analysis was conducted using multiple Mann-Whitney U tests.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA tendency towards higher ISQ values in the implants indicated for the early loading protocol was observed, whereas there was no significant difference in the ISQ values overall. For Straumann implants, SLActive\u003csup\u003e\u0026reg;\u003c/sup\u003e demonstrated a marginally higher removal torque value than the SLA\u003csup\u003e\u0026reg;\u003c/sup\u003e group at 2 weeks (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.068). Micro-CT analysis further showed that the RGV of dental implants in the early loading group (Inicell\u003csup\u003e\u0026reg;\u003c/sup\u003e) was significantly higher than that in the normal implant group (SPI\u003csup\u003e\u0026reg;\u003c/sup\u003e) at 2 weeks (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Moreover, histomorphometrical analysis showed a significantly higher value of BV/TV ROI 1 in the early loading group (Inicell\u003csup\u003e\u0026reg;\u003c/sup\u003e) than the normal control group (SPI\u003csup\u003e\u0026reg;\u003c/sup\u003e) at 2 weeks (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThese results, comparing SLActive\u0026reg; with SLA\u0026reg; of Straumann, and Inicell\u0026reg; with SPI\u0026reg; of Thomenn in rabbit tibia, suggest that dental implants indicated for early loading protocol may exhibit superior osseointegration and periosteogenesis, particularly during the initial healing stage.\u003c/p\u003e","manuscriptTitle":"Effectiveness of dental implants indicated for early-loading protocols on peri- implant bone healing: An animal study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-07 11:58:55","doi":"10.21203/rs.3.rs-6937587/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":"27ae183a-fab5-456c-ac94-acd153b420ed","owner":[],"postedDate":"August 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-05T22:08:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-07 11:58:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6937587","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6937587","identity":"rs-6937587","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}