Immune response to implant surface decontamination methods in the surgical peri-implantitis management

Immune response to implant surface decontamination methods in the surgical peri-implantitis management | 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 Immune response to implant surface decontamination methods in the surgical peri-implantitis management Rakasevic Dragana, Aleksic Zoran, Lazic Zoran, Soldatovic Ivan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7575328/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: The study assessed the efficacy of different implant surface decontamination methods in surgical peri-implantitis (PI) treatment, considering the immune response. Material and Methods: Forty-four patients (aged 58.7 ± 9.4) dignosed with 52 peri-implantitis (peri-implant probing depth, (PPD) > 5 mm, bleeding on probing (BOP “+”), and bone loss > 2 mm) completed a two-year study. ISD was employed by either photodynamic therapy (PDT, test group) or 1% chlorhexidine di-gluconate gel (control group) followed by peri-implant bone defects reconstruction. Interleukins (IL) 17A, IL-1β, and IL-6 concentrations, clinical and radiographic outcomes were assessed throughout 24 months postoperatively. Results: IL-17A, IL-1β, and IL-6 concentrations were significantly reduced 24 months postoperatievly (p = 0.007, p < 0.001, and p = 0.006) in the test group compared to the control one. A statistically significant decrease in terms of PPD was achieved in the test compared to the control group at 12 and 24 months postoperatively (p= 0.036, p= 0.043). Conclusion: PDT may provide a feasible method for implant surface decontamination, improving immune response in reconstructive peri-implantitis treatment. Clinical relevance: A reconstructive peri-implantitis surgery combined with PDT effectively decreases pro-inflammatory interleukin during the first 24 months postoperatively, significantly enhancing clinical and radiographic outcomes. Study was registered retrospectively at ClinicalTrials.com (NCT05187663). peri-implantitis photodynamic therapy implant surface decontamination pro-inflammatory interleukin reconstructive therapy Figures Figure 1 Figure 2 Figure 3 1. Introduction Peri-implantitis is defined as a biofilm-mediated inflammatory condition [1], that, if left untreated, leads to implant loss. The host's susceptibility to pathogens and released titanium particles [2] triggers deleterious immune-mediated host-tissue responses [3], inducing a cascade reaction of bone-resorption-mediated interleukins (ILs)-1β, TNF-α, IL-10, IL-6, IL-17 [4, 5]. This results in osteoclastic differentiation and osteoclastogenesis [6, 7], increasing bone loss severity. Moreover, IL-17 by negative feedback maintains inflammation and supports aggressive disease progression. Therefore, understanding IL's role in peri-implantitis pathogenesis could be crucial to develope effective treatment strategies to modulate the host's immune response in peri-implantitis, reduce inflammation, restore tissue homeostasis, and ultimately improve clinical outcomes. Peri-implantitis therapy was based initially on the principle of periodontitis treatment, employing mechanical methods combined with anti-inflammatory/antibacterial approaches [8]. The distinct structural features of peri-implantitis and implant surfaces as opposed to periodontitis and natural roots [9] indicate that implant surface decontamination (ISD) is an crutial step in both non-surgical and surgical therapy. ISD aims to eliminate pathogens and their products from implant surface to maintain implant biocompatibility, chemical composition, and roughness, arresting the disease progression and possibly allowing tissue regeneration [10]. Several proposed ISD methods, including mechanical (e.g. ultrasonic devices, metal curettes [11]) and chemical (citric acid [12]), demonstrate potential implant surface damage or alteration, increasing roughness, corrosion, and titanium particle release, and contributing to disease recurrence [13, 14]. As a chemical agent, chlorhexidine (CHX) is one of the most widely used bisbiguanide antiseptics, available in solutions, chips and gels. In addition to its antibacterial properties, CHX demonstrated to have a dose-dependent cytotoxic effect on fibroblasts [15-17]. However, research on CHX's effect on immunomodulation [17] in surgical peri-implantitis treatment remains scarce. Subantimicrobial systemic antibiotic administration appears to play a host-modulating role and a notable positive short-term outcome on clinical parameters [18], however, antibiotics are associated with bacterial resistance and harmful side effects [19, 20]. To address this issue, photodynamic therapy (PDT) emerges as a promising adjunctive therapy [21] that can immunomodulate the host response [22] in peri-implant tissues as an alternative to antibiotics [23] without altering implant surface [14, 24, 25]. PDT's working mechanism is based on binding target cells to an engaging photosensitizer (PS), activated by diode laser irradiation. Through interaction with tissue oxide, PS induces a single oxygen onset, causing a toxic effect on pathogen cells and consequently, their death [26]. Numerous experimental [25, 27], animal [28, 29], non-surgical [23, 30], and surgical studies [31-33] demonstrated undeniable microbiological decontamination and partial bone formation at various implant surfaces uitlizing PDT. Nevertheless, PDT's influence on bone-mediated inflammatory ILs and possible immunomodulation in reconstructive peri-implantitis treatment is still limited. Considering a lack of a comprehensive ISD protocol for peri-implantitis, this study aimed to determine whether different ISD methods modulate immune response, enhancing clinical and radiographic outcomes, 24 months after peri-implantitis reconstructive surgery. 2. Material and Methods 2.1 Study design and Patient selection The study was designed based on a previously published randomised clinical trials, RCT [31], accoridng to Declaration of Helsinki of 1975, revised in 2004, and CONSORT 2010 statement. Prior to the study, the local Ethics Committee of School of Dental Medicine, University of Belgrade, approved the study (number 36/28). Eighty-one patients with peri-implantitis signs were screened and recruited from January 2014 to December 2017. Only patients meeting all eligibility criteria were enrolled in the study: Aged > 18 years old with ability to sign inform consent; Systematically healthy or with mild or moderate well-controlled systemic conditions or diseases; No systemic antibiotic medication and anti-inflammatory drugs within the last 3 months; Presence of at least one prosthetically rehabilitated implant (bone- or tissue- level) in the function ≥ 1-year with peri-implantitis signs. Peri-implantitis was defined: Peri-implant probing depth (PPD) ≥ 5 mm with positive sign of bleeding on probing (BOP ‘’+’’) and/or suppuration at least one side around the implant, and radiographic bone lost < 2 mm [34] (Figure 1 a, b, c). Implant malposition, radiographic bone loss ≥ two-thirds (severe peri-implantitis) with or without implant mobility; previous surgical peri-implantitis treatment within last 6 months; heavy smoking habit (>10 cigarettes/day); presence of systemic diseases including diabetes mellitus, leukaemia, musculoskeletal diseases and disorders or uncontrolled systemic diseases (ASA type III); earlier head and neck radiation therapy; uses high-dosed of antiresorptive drug (i.e., bisphosphonate), immunosuppressors; pregnancy and lactation, were considered as excusion criteria. 2.2 Outcome variables Clinical and radiographic examination Clinical parameters including PPD, clinical attachment level (CAL), BOP, plaque index (Pi) score, mucosal recession (MR), were measured at baseline, six, 12, and 24 months after the surgery using a graduated periodontal probe (PCPUNC 15, Hu Friedy, Chicago, USA), with 0.25 N force. Whenever required and if the periodontal probe could not reach the area around the implant, the crown was removed. Assessment of periapical radiographs were obtained from the same implants utilizing the long cone paralleling technique. Radiographic bone level (RBL) changes were estimated around the implant, measured from the prosthetic connection platform to the bottom of the defect before and at 12 and 24 months postoperatively. Clinical and radiographic examinations were performed by the two blind and calibrated periodontists (DR, ZA). To establish inter-examiner reliability, five implants with diagnosed peri-implantitis were included. The first four measurements of PPD (clinical variable) and 10 measurements of BL (radiographic variable) were repeated 24 hours apart. Calibration was accepted if inter-examiner reproducibility resulted in inter-class correlation coefficients of 0.94 (CI 95% 0.90 to 0.96, standard error (SE) 0.12) for PPD and 0.90 (CI 95% 0.89 to 0.95, standard error (SE) 0.19) for radiographic BL. Immunological samples and analyses Peri-implant crevicular fluid (PICF) samples were collected from each implant previously diagnosed with peri-implantitis [7] using standard paper strips (Periopaper, Oralflow Inc., Smithtown, NY, USA). A calibrated Periotron (Periotron® 6000, Interstate Drug Exchange, Amityville, NY, USA) was utilized to measure PICF volume, after which paper strips were inserted in micro-centrifuge plastic tubes and immediately stored at -70 ºC until further processing. Blood-contaminated strips were discharged. Samples were vortexed for 10 sec and centrifuged for 5 min at 3000 g before final analyses. The quantitative detections of human IL-1β, IL-6, and IL-17A in PICFs were determined employing enzyme-linked immunosorbent assay (ELISA) using commercially available ELISA kits (Human IL-1β / IL-6 / IL-17A High Sensitivity ELISA, Bender MedSystems GmbH, Vienna, Austria). The assay procedure specified in the manufacturer´s product manual was followed for each kit to obtain optimal test performance. In brief, the absorbance of each micro-well was read on a Multiskan EX spectrophotometer (Thermo Electron Corporation, Vantaa, Finland) using 450 nm as the primary wavelength. Concentrations of ILs for each sample were assessed from standard curves by interpolation. Standard curves were generated for each tested interleukin by plotting the absorbance for each standard concentration on the Y-axis against the known standard concentration on the X-axis. Results were expressed as pg of sample/ ml of PICF volume. 2.3 Intervention with implant surface decontamination Peri-implantitis was treated surgically performing regenerative approaches to reconstruct peri-implant bone defects (PIBD) according to the procedure described earlier [31]. Briefly, two weeks before surgery, each patient underwent full-mouth non-surgical treatment and oral hygiene instruction, along with single mechanical debridement around implant diagnosed with peri-implantitis. Before ISD during the surgery, a non-transparent white envelope was used to randomise patients into one (test) group employing PDT (HELBO, Photodynamic Systems GmbH, Wels, Austria) and another contol group using CHX (Chlorhexamed® – Direkt; GlaxoSmithKline, GmbH & Co. KG, Munich, Germany). In the test group, phenothiazine chloride (10 mg/mL of HELBO® Blue Photosensitizer), was applied onto the implant surface (3 min) and fullfilled PIBD, following saline solution irrigation and laser light exposure (180 sec/implant) (HELBO ® TheraLite Laser, 660 nm, 100mW, total dose of 44 J/cm2) (Figure 2 a-c). In the control group, 1% CHX gel was applied directly onto the implant surface (1 min), followed by abundant saline solution irrigation (1 min). Precaution was taken to avoid contact between the bone and the CHX gel. Subsequently, PIBDs were reconstructed using bovine bone substitute and collagen membrane (Bio-Oss® and Bio-Gide®, Geistlich Pharma, AG, Wolhusen, Schweiz) (Figure 2d). A systemic antibiotic (Amoxicillin, 500 mg or, in case of allergy, Clindamycin, 600 mg, Hemofarm, Serbia, three times per day for 5 days) was prescribed postoperatively along with oral hygiene reinforcement. Antiseptics and painkillers were not recommended during the procedure. Follow-up controls involved supportive peri-implant care (SPIC) aiming to maintain achieved results every three months within the period of 24 months. SPIC considered oral hygiene reinforcement and mechanical plaque removal. 2.4 Data analyses The sample size was set according to study Schwarz et al. [35] in which total BOP were reduced for 85.2 ± 16.4% and 71.6 ± 24.9% performing the two divers ISD methods (plastic curets and cotton pellets vs. Er:YAG laser). Using a two-sample equal-variance t-test with 80% power to reject the null hypothesis of equal means, α= 0.05, with 10% drop-out rates and if SD would not exceed 15%, a total of 26 implants per group were required. BOP and concentrations of IL-6, IL-17A, and IL-1β were considered as primary outcomes while secondary outcomes were PPD, CAL, Pi score, MR, RBL, and patients’ and implants’ demographic parameters. Statistical analyzes were performed by using SPSS 20.0 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.) and R 3.4.2. (R Core Team (2017), R Foundation for Statistical Computing, Vienna, Austria). Results are presented as count (%), means ± SD or median (25 th -75 th Percentile) depending on data type and distribution. To assess correlation between variables Pearson and Spearman correlation was used. Linear mix model (LM) was emplyed to determinate the relationship between change of dependent variable and treatment adjusted for other variables. The model used the following formula: interleukins = group*time + group + time + clinical parameters. All p values < 0.05 were considered significant. 3. Results Out of 81 patients evaluated, 48 were eligible for inclusion and enrolled in the study. Four patients were excluded from further analyses (two in the control group and two in the test group) reported acute infection signs (swelling and suppuration), antibiotic intake a week before a six-month follow-up appointment, and an one patient never showed up for an appointment (CONSORT Flow Chart). Demographic and implant-based factors are presented in Table 1. No side effects and implant loss were reported at 24 months follow-up. Initial (PPD < 5 mm) and moderated (6 < PPD < 8 mm) stages of peri-implantitis (n= 52)[36] were treated in 44 patients (mean ages 58.7 ± 9.4). Peri-implantitis was mostly detected in the posterior part of the mandible (63.4%), with statistically significant differences among the regions (p= 0.019). 3.1 Clinical, radiographi, and immunological outcomes A significant improvement in clinical and radiographic parameters was observed within the tested groups 12 and 24 months postoperatively (p > 0.05) (Table 2 a, b; Figure 2 e, f, g). BOP decreased in both groups, however, a slightly greater reduction was observed in the test group at 12 months postperatievly (p = 0.048). At 24 months, a statistically significant reduction in PPD was gained in the test compared to control group (Δ baseline - 24 months, p = 0.043). No statistical differences were found among groups regarding IL-17A, IL-6, and IL-1β concentrations prior to treatement (Table 3). Nevertheless, compared to the control group, the test group achieved significantly greater reductions in followed ILs (p <0.001). While ILs' concentrations continued to decrease significantly in the test group, a trend of ILs rising was recorded in the control group. Utilizing LM model the positive correlation was detected between clinical parameters such as PPD and ILs concentration changes (Figure 3 a, b, c). The increases in IL-1β were statistically related to increases in IL-6 (p = 0.046), PPD (p = 0.010), and CAL (p = 0.013). Moreover, PDT interacting with reduction of IL-1β was significantly related to IL-6 concentration (p= 0.007) and PPD decreases (p= 0.041), and CAL gained (p= 0.004) at 12 months postoperatively, yet without statistical differences at 24 months. Conversely, CHX interacting with a greater IL-17 concentration showed correlation with increases in terms of IL-1β and PPD at 12 and 24 months. No significant correlation was found between detected infra-bony defects and the following ILs. 4. Discussion The present RCT was conducted to evaluate the immune response induced by two diverse ISD approaches in reconstructive peri-implantitis therapy. According to the study's findings, ISD of moderate implant surface roughness (75%) employing PDT, as compared to CHX application, reduced statistically significantly pro-inflammatory IL-17A, IL-1β, and IL-6 concentrations, associated directly with significant improvements in clinical parameters, specifically PPD, at 12 and 24 months (p = 0.036, p = 0.013). Additionally, PDT engagement was associated with greater reductions in BOP and significant increases in radiographic bone levels (p = 0.04) following surgery. An aggressive and rapid bone resorption in peri-impantitis is caused by a host immune response, initiated by different cell types, including T cells, which stimulate a cascade reaction of pro-inflammatory cytokines [37] such as IL-17A, IL-1β, and IL-6. Furthermore, implant surface features, including implant macro- and micro-topography, wettability, and hydrophilicity [12], influence immune system response during peri-implantitis. Despite the ability to influence early and rapid osseointegration, rough and modified layers of implant surfaces are prone to plaque accumulation and biofilm formation. As a result, it hinders effective microorganism removal, modifies implant surface properties, and thus alters immune responses, causing peri-implantitis. Therefore, an appropriate ISD is essential for treating peri-implantitis efficiently to arrest disease progression, allowing tissue to regenerate. Ideally, an ISD method in peri-implantitis therapy should remove all deposits from the implant surface without affecting surface biocompatibility or integrity, while simultaneously suppressing bacteria regrowth [13], supporting immune response, and significantly influencing the re-osseointegration [10, 21]. Various mechanical and chemotherapeutic agents displayed successful clinical and radiographic outcomes [19, 38, 39] following peri-implantitis therapy, however, studies revealed greater surface alteration, changes in surface energy and wettability when these methods were utilised [12]. Consequently, this could affect a host's immune response, impairing tissue regeneration. Mechanical methods, including scalers and metal curettes, showed severe damage to the implant surface, increasing roughness and bacterial adherence, and titanium (TP) particles release [2]. Some chemotherapeutic agents may damage the implant surface, causing corrosion, which, along with TP release and biofilm formation, may encourage neutrophils and macrophages to secrete pro-inflammatory cytokines directly or indirectly, inducing further bone resorption. Accordingly, photodynamic therapy, PDT, is an effective method of microorganism reduction in non-surgical peri-implantitis treatment [23], resulting in IL-17 and IL-1β decreases and demonstrating any alteration of zirconium or titanium surfaces in vitro [24, 25]. PDT produces reactive oxygen species (ROS), which damage microbial cells [40], activate cell signalling pathways, release inflammatory mediators, and modulate immune responses [41]. The eradication of peri-implantitis pathogens from different titanium surfaces was demonstrated earlier by employing PDT and regenerative surgical techniques [42-44]. Results showed a reduction in inflammation signs, including BOP and pro-inflammatory ILs, along with an enhancement of clinical parameters. This is consistent with the present study, which found a greater reduction of PPD when PDT was used for ISD compared to 1% CHX gel at 24 months following peri-implantitis surgery (Δ baseline- 24 months, p = 0.043). Additionally, PPD interacting with PDT was positively correlated with CAL gain and IL-1β, IL-17A, and IL-6 decreases at 12- and 24-month postoperatively. Furthermore, BOP reduction was positively influenced by a decrease in pro-inflammatory ILs after 12 months (p = 0.048), suggesting that these ILs are crucial to determining peri-implantitis severity. IL-1β behaves as a powerful stimulator of osteoclast cell differentiation and bone resorption. It was often detected in high levels along with IL-6 in patients with peri-implantitis [4, 5], similar to our findings. A synergistic effect between ILs influencing PPD changes and positive BOP was observed in our study, supporting the importance of these ILs as indicators of treatment success. Moreover, both methods applied for ISD resulted in IL-17A reduction after 6 months. Recent studies [45] demonstrated a reduction in IL-17A level, albeit without statistical significance, following open flap peri-implantitis surgery combined with ISD employing mechanical methods, saline irrigation, air polishing, and 2% chlorhexidine irrigation. Additionally, this 3-month study [45] showed a decrease in IL-1β, IL-6, disrupting the correlation between TNF-α with IL-17A, and IL-1β, and significantly improving clinical outcomes. Although the above-mentioned and present studies have shown a reduction in pro-inflammatory ILs in the short term, our study reveals ILs increases at 12 and 24 months when 1% CHX gel was used for ISD. As a broad-spectrum bactericidal and bacteriostatic agent, CHX was previously utilized in peri-implantitis therapy. Nevertheless, supporting our findings, a small number of studies have failed to demonstrate CHX's significance in surgical peri-implantitis treatments [46-48]. Despite the limited studies, CHX appears to alter the implant surface, affecting wettability, and exhibits cytotoxic effects on fibroblasts and mesenchymal cells [15-17]. Even so, an in vitro study didn't reveal that 1% CHX impaired osteoblasts [49]. The reason could be that CHX is a time-dependent agent, which implies that the short exposure time of the implant surface (1 minute) may be insufficient to harm peri-implant cells and increase ILs. However, possible differences compared to PDT could be attributed to CHX's inability to eliminate pathogens and their products from the surface, leaving their biofilm remnants adherent to the surface. This could alter surface energy, inducing an immune response, decreasing osteoblast adhesion and maturation, and subsequently, disease recurrence [12, 50]. This might be an explanation for the pro-inflammatory ILs increases in this study, resulting in inflammation recurrence and bone resorption. Thus, the consequent bone resorption in the control group might be explained by the overexpression of IL-17A, which induces osteoblast precursors to generate inflammatory factors, such as IL-1β and IL-6, up-regulating osteoclast activity [51]. IL-17A promotes osteoclast activation and pro-inflammatory ILs release, indicating that it plays an important role in osteoclastogenesis [52], along with RANK. The fact that osteoclast activity is mediated by IL-17A concentration suggests that suppressing IL-17A may cause a decrease in IL-6 and IL-1β. Consequently, bone loss may be suppressed, encouraging bone formation. Accordingly, present results indicated that adjuvant PDT could decrease pro-inflammatory ILs such as IL-17A, IL-6, and IL-1β. Furthermore, reduction of these ILs combined with PIBD reconstruction may also influence the possibility of bone gain, potentially enhancing re-osseointegration. The possibility of bone formation on previously decontaminated surfaces was early demonstrated [53] determining partial re-osseointegration (59.2%) of ligature-induced peri-implantitis using PDT and guided bone regeneration (BioOss® and BioGide®)[29]. Long-term outcomes demonstrated significant bone gain with stable outcomes after ISD with PDT and PIBD reconstruction in the treatment of moderate and sever peri-implantitis [33, 54], similar to present 24-month outcomes. Another explanation for the successful results might be the exposure time to photosensitizers and laser. According to animal studies, PTD affects peri-implant pocket reduction [55] and significant bone gain [28] when more than one minute of PS is delivered to the treated area, followed by > 80 seconds/implant of light irradiation. Therefore, 3 minutes of PS exposure and 180 seconds of irradiation/implant combined with SPIC may explain stable clinical outcomes after 24 months. Further, low-level laser radiation stimulates cell proliferation and regeneration such as osteoblasts [56], explaining the additional bone gain following PDT. In addition to the small sample size, the study limitation could be the independent ELISA analyses of ILs and the inability to assess other bone metabolism and mediators, such as TNF alpha and RANKL. This might limit the insight into the true dynamics of ILs interplay in surrounding peri-implant tissues. 5. Conclusion Implant surface decontamination utilising PDT combined with a reconstructive surgical approach could be considered an effective method for peri-implantitis management, resulting in decreased pro-inflammatory ILs and clinical and radiographic outcomes enhancement. Declarations Conflict of Interest The authors declare no competing interests. Founding No funding was obtained for this study. Ethical approval The study was approved by the local Ethics Committee of School of Dental Medicine, University of Belgrade. Ethical approved number 36/28. Affiliation: Ethics Committee of the School of Dental Medicine University of Belgrade, Belgrade, Serbia.(www.stomf.bg.ac.rs; e-mail: [email protected] ). I nformed Consent Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper. Authors’ contributions: All authors contributed to the study conception and design. All authors read and approved the final manuscript. Conceptualization: R.D., M. A., A.Z., L.Z.; Methodology: L.Z, R.D., M. A., A.Z.; Formal analysis and investigation: R.D., S. I; Figure prepared by: R.D., S. I; Writing - original draft preparation: R.D.; Writing - review and editing: R.D., A.Z., M.A.; Supervision: A.Z., M.A. References Schwarz, F., et al., Peri-implantitis. J Periodontol, 2018. 89 Suppl 1 : p. S267-s290. 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A 12-month prospective clinical study. Clin Oral Implants Res, 2012. 23 (2): p. 205-10. Irshad, M., et al., Effects of Implant Surface Debridement and Systemic Antibiotics on the Clinical and Microbiological Variables of Periimplantitis. Biomed Res Int, 2021. 2021 : p. 6660052. Cai, Z., et al., Antimicrobial effects of photodynamic therapy with antiseptics on Staphylococcus aureus biofilm on titanium surface. Photodiagnosis Photodyn Ther, 2019. 25 : p. 382-388. Aebisher, D., P. Woźnicki, and D. Bartusik-Aebisher, Photodynamic Therapy and Adaptive Immunity Induced by Reactive Oxygen Species: Recent Reports. Cancers, 2024. 16 (5): p. 967. Haas, R., et al., Elimination of bacteria on different implant surfaces through photosensitization and soft laser. An in vitro study. Clin Oral Implants Res, 1997. 8 (4): p. 249-54. Dortbudak, O., et al., Lethal photosensitization for decontamination of implant surfaces in the treatment of peri-implantitis. Clin Oral Implants Res, 2001. 12 (2): p. 104-8. Rakašević, D. and D. Gabrić, The Effect of Implant Surface Design and Their Decontamination Methods in Peri-Implantitis Treatment , in Current Concepts in Dental Implantology , G. Dragana and V. Marko, Editors. 2021, IntechOpen: Rijeka. p. Ch. 12. Gonçalves, L., et al., The Effect of Peri-Implant Therapy on the Expression of Th17-Related Cytokines in Patients with Peri-Implant Mucositis and Peri-Implantitis: A Prospective Longitudinal Study. J Clin Med, 2025. 14 (2). de Waal, Y.C., et al., Implant decontamination with 2% chlorhexidine during surgical peri-implantitis treatment: a randomized, double-blind, controlled trial. Clin Oral Implants Res, 2015. 26 (9): p. 1015-23. Wilensky, A., et al., The efficacy of implant surface decontamination using chemicals during surgical treatment of peri-implantitis: A systematic review and meta-analysis. J Clin Periodontol, 2023. 50 Suppl 26 : p. 336-358. Roccuzzo, M., et al., Surgical therapy of peri-implantitis lesions by means of a bovine-derived xenograft: comparative results of a prospective study on two different implant surfaces. J Clin Periodontol, 2011. 38 (8): p. 738-45. Verdugo, F., et al., Bone microbial decontamination agents in osseous grafting: an in vitro study with fresh human explants. J Periodontol, 2011. 82 (6): p. 863-71. Lee, B.S., et al., Surface property alterations and osteoblast attachment to contaminated titanium surfaces after different surface treatments: An in vitro study. Clin Implant Dent Relat Res, 2018. 20 (4): p. 583-591. Van bezooijen, R.L., et al., Interleukin-17: A new bone acting cytokine in vitro. J Bone Miner Res, 1999. 14 (9): p. 1513-21. Lee, Y., The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases , in BMB Rep . 2013. p. 479-83. Renvert, S., I. Polyzois, and R. Maguire, Re-osseointegration on previously contaminated surfaces: a systematic review. Clin Oral Implants Res, 2009. 20 Suppl 4 : p. 216-27. Etemadi, A., H. Sabri, and M. Enssi, Surgical reconstruction of peri-implantitis with adjunctive antimicrobial photodynamic therapy: A case report with 5-year follow-up. Clin Adv Periodontics, 2024. 14 (3): p. 185-191. Madi, M. and A.S. Alagl, The Effect of Different Implant Surfaces and Photodynamic Therapy on Periodontopathic Bacteria Using TaqMan PCR Assay following Peri-Implantitis Treatment in Dog Model. Biomed Res Int, 2018. 2018 : p. 7570105. Miranda, J.M., et al., Photobiomodulation Therapy in the Proliferation and Differentiation of Human Umbilical Cord Mesenchymal Stem Cells: An In Vitro Study. J Lasers Med Sci, 2020. 11 (4): p. 469-474. Tables Table 1. Socio-demographic, restorative, and implant-based variables at baseline Test group Control group Total p -value Age, mean ± SD 58.7 ± 9.4 Gender, N (%) Male 18 (82) 16 (73) 34 (77.3) 0.132 Female 4 (18) 6 (27) 10 (22.7) Period of implant loading, (years, mean ± SD) 7.01±3.52 History of treated periodontitis, N (%) Yes 14 (64) 16 (72) 30 (65) 0.335 No 8 (36) 6 (28) 14 (35) Smokers ( < 10 cigarettes), N (%) 2 (10) 1 (5) 3 (5) 0.987 Number of treated implants 26 26 52 0.213 Location, n (%) Maxilla 7 (27) 6 (24) 13 (25) 0.866 Mandible 19 (73) 20 (76) 39 (75) Region, n (%) Premolar 8 (31) 11 (42) 19 (37) 0.019* Molar 18 (69) 15 (58) 33 (63) Implant surface, n (%) MTX 4 (15) 3 (12) 7 (13) 0.192 Ossteospead 5 (19) 6 (24) 11 (21) TiUnite 11 (42) 10 (38) 21 (40) BCT 6 (24) 7 (26) 13 (25) Surface roughness, n (%) Moderate 20 (77) 19 (74) 39 (75) 0.689 Smooth 6 (23) 7 (27) 13 (25) Type of restoration, n (%) Single crown, cement-retained 15 (58) 13 (50) 28 (54) 0.087 Partial or full-arch bridge, cement-retained 7 (27) 9 (35) 16 (31) Implant-supported prosthesis 4 (15) 4 (15) 8 (15) Osseous defects, n (%) Class 1 b 9 (35) 12 (46) 21 (40) 0.177 Class 1 d 9 (35) 8 (30) 17 (33) Class 1 e 8 (30) 6 (24) 14 (27) PPD, n (%) > 5 mm 15 (58) 15 (58) 30 (58) 0.278 > 6 mm 11 (42) 11 (42) 22 (42) > 8 mm 0 (0) 0 (0) 0 (0) RBL at mesial site, n (%) > 2 mm 9 (35) 7 (27) 16 (31) 0.129 > 3 mm 13 (50) 14 (54) 27 (52) > 4 mm 4 (15) 5 (20) 9 (17) RBL at distal site, n (%) > 2 mm 11 (42) 12 (46) 23 (45) 0.683 > 3 mm 10 (38) 10 (38) 20 (38) > 4 mm 5 (19) 4 (15) 9 (17) † n- number of implant diagnosed with peri-implantitis presented in percentages (%) ; N- number of subject with peri-implantitis presented in percentages. ‡ MTX- Acid washed surface, (Zimmer Biomet Dental, Carlsbad, CA, USA); TiUnite- Porous anodized surface (Nobel BioCare, Gothenburg, Swede); Osseospeed- Fluoride-modified titanium dioxide grit-blasted (AstraTech, Mölndal, Sweden), BCT- Machined polished implant surface (BCT Implant System, SCG, Serbia); PPD- distribution of peri-implant probing depth presented in millimetres before any treatment; RBL- distribution of marginal bone loss (peri-implantits severity[34]) based on radiographic analyses presented in millimetres before treatment. *Statistically significant differences in changes ( p < 0.05). Table 2a. Clinical outcomes variables on implants level at baseline, and six, 12, and 24 months after the surgical procedure. Test group (n = 26) Control group (n = 26) p -value PPD, mean ± SD baseline 5.38 ± 0.7 5.41 ± 1.15 0.378 6 months 2.52 ± 0.6* 2.94 ± 0.8 0.257 12 months 2.50 ± 0.55* 3.06 ± 1.16 0.036 ** Δ baseline - 12 months 2.88 ± 0.6 2.35 ± 1.05 0.083 24 months 2.32 ± 0.42* 3.01 ± 1.03* 0.013 ** Δ baseline - 24 months 2.96 ± 0.55 2.4 ± 0.93 0.043 ** CAL, mean ± SD baseline 5.17 ± 1.3 5.27 ± 1.24 0.367 6 months 2.56 ± 1.04 2.89 ± 0.86 0.225 12 months 2.52 ± 0.97* 2.97 ± 1.12 0.130 Δ baseline - 12 months 2. 65 ± 1.31 2.29 ± 1.27 0.083 24 months 2.43 ± 0.91* 2.95 ± 1.2* 0.095 Δ baseline - 24 months 2.74 ± 1.37 2.32 ± 1.15 0.081 MR, mean ± SD baseline 0.74 ± 0.9 0.69 ± 0.95 0.476 6 months 0.58 ± 0.76 0.56 ± 0.8 0.612 12 months 0.54 ± 0.75 0.53 ± 0.87 0.463 Δ baseline - 12 months 0.2 ± 0.62 0.16 ± 0.6 0.574 24 months 0.54 ± 0.87 0.57 ± 0.89 0.45 Δ baseline - 24 months 0.2 ± 0.05 0.12 ± 0.03 0.077 BOP, mean ± SD baseline 86 ± 19 83.94 ± 26.3 0.761 6 months 0.2 ± 1.1 0.62 ± 3.21 0.336 12 months 0.67 ± 3.33* 6.17 ± 15.4* 0.048 ** Δ baseline - 12 months 85.33 ± 18.8 77.76 ± 26.98 0.445 24 months 4.67 ± 9.03* 8.02 ± 12.55* 0.169 Δ baseline - 24 months 81.33 ± 24.21 75.91 ± 36.22 0.413 Pi, mean ± SD baseline 96.7 ± 6.8 85.18 ± 23 0.141 6 months 10.67 ± 17.3 17.28 ± 11.2 0.139 12 months 7.3 ± 11.8 14.8 ± 20.1 0.286 Δ baseline - 12 months 89.33 ± 5 70.30 ± 2.9 0.004 ** 24 months 8.4 ± 4 14.2 ± 12.2 0.006 ** Δ baseline - 24 months 88.3 ± 2.8 71 ± 10.8 0.001 ** § SD, standard deviation; ¶ PPD, peri-implant probing depth; CAL, clinical attachment level; MR, mucosal recession; BOP, bleeding on probing; Pi, Plaque index score; PPD, CAL, MR expressed in mm; BOP and Pi expressed as percentage. * Time-related within-group statistically significant difference baseline vs 12 months; baseline vs 24 months; p< 0.001; analyzed by t test or Wilcoxon Signed-Rank test; ** Statistically significant difference between the groups by t test or Mann-Whitney Test (p < 0.05). Table 2b. Radiographic bone level, RBL changes assessed on implants level at baseline, and 12 and 24 months after the surgical procedure. Test group (n = 26) Control group (n = 26) p -value RBL, mesial side, mean ± SD baseline 3.21 ± 0.9 3.33 ± 1.1 0.662 12 months 0.4 ± 0.21* 0.6 ± 0.46* 0.029 ** Δ baseline - 12 months 2.81 ± 0.69 2.73 ± 0.05 0.405 24 months 0.6 ± 0.24* 1.1 ± 0.42* < 0.001 ** Δ baseline - 24 months 2.61 ± 0.66 2.23 ± 0.68 0.117 RBL, distal side, mean ± SD baseline 2.2 ± 0.75 2.1 ± 0.75 0.667 12 months 0.3 ± 0.23* 0.61 ± 0.3* 0.041 ** Δ baseline - 12 months 1.97 ± 0.67 1.5 ± 0.73 0.043 ** 24 months 0.3 ± 0.22* 0.7 ± 0.31* 0.786 Δ baseline - 24 months 1.98 ± 0.72 1.41 ± 0.71 0.045 ** § SD, standard deviation; * Time-related within-group statistically significant difference baseline vs 12 months; baseline vs 24 months; p< 0.001; analyzed by t test or Wilcoxon Signed-Rank test; ** Statistically significant difference between the groups by t test or Mann-Whitney Test (p < 0.05). Table 3. Immunological outcomes measured and their changes among baseline, six, 12 and 24 months after the surgery. Test group (n = 26) Control group (n = 26) p-Value IL-6 , mean ± SD baseline 0.56 ± 0.37 0.86 ± 0.991 0.456 6 months 0.27 ± 0.2 0.59 ± 0.85 0.046** 12 months 0.14 ± 0.22 1.01 ± 0.2 0.004** Δ baseline -12 months 0.42 ± 0.33 -0.15 ± 0.7 0.012 24 months 0.23 ± 0.24 0.73 ± 0.8 0.006** Δ baseline - 24 months 0.33 ± 0.36 0.13 ± 0.65 0.133 IL - 1 β, mean ± SD baseline 75.32 ± 39.29 93.72 ± 39.27 0.081 6 months 26.43 ± 7.67 59.5 ± 30.79 <0.001** 12 months 30.21 ± 17.71 80.59 ± 51.9 <0.001** Δ baseline -12 months 45.11 ± 36.74 13.124 ± 45.84 0.033 24 months 28.42 ± 20.58 88.37 ± 55.43 <0.001** Δ baseline - 24 months 46.9 ± 41 5.35 ± 48.28 0.012 IL-17A, mean ± SD baseline 4.26 ± 1.05 4.31 ± 1.94 0.921 6 months 2.66 ± 1.03 3.61 ± 1.53 0.012** 12 months 2.98 ± 1.5 4.47 ± 1.81 0.002** Δ baseline -12 months 1.3 ± 1.98 -0.16 ± 1.62 0.006 24 months 2.93 ± 1.32 4.61 ± 2.74 0.007** Δ baseline - 24 months 1.33 ± 1.99 -0.29 ± 2.54 0.013 § SD, standard deviation; * Time-related within-group statistically significant difference baseline vs 12 months; baseline vs 24 months; p< 0.001; analyzed by t test or Wilcoxon Signed-Rank test; ** Statistically significant difference between the groups by t test or Mann-Whitney Test (p < 0.05). Additional Declarations No competing interests reported. Supplementary Files Suppl..pdf 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7575328","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":519190087,"identity":"24012e41-e8de-4251-9e37-8f4244e927f5","order_by":0,"name":"Rakasevic Dragana","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDCCA3CCsYHhA5BiYydFC+MMkBZm4rUwMDDzgEkCOvhuH2D78OOMnT2/RHLjZ5tf2+T5mBkYP3zMwa1F8lwC88yeG8mJM2ckNkvn9t02bGNmYJacuQ23FoMzQIfwfGBOMDhzsI05t+c2I1ALGzMvAS2Mfz7U29uDtFj23LYnSgszz43DjBvYG4GKf9xOJKhF8gxjM7PMmeOJM443Nkv2NtxObmNmbMbrF74zzIcZ3xyrtudvZn/44cef27bz25sPfviIRws40hHsNnQRwuAPKYpHwSgYBaNgpAAAo+FRaCoGIrEAAAAASUVORK5CYII=","orcid":"","institution":"University of Belgrade","correspondingAuthor":true,"prefix":"","firstName":"Rakasevic","middleName":"","lastName":"Dragana","suffix":""},{"id":519190088,"identity":"e232d086-e247-4533-b028-b91d1268c8f6","order_by":1,"name":"Aleksic Zoran","email":"","orcid":"","institution":"University of Belgrade","correspondingAuthor":false,"prefix":"","firstName":"Aleksic","middleName":"","lastName":"Zoran","suffix":""},{"id":519190089,"identity":"f3670759-ef73-438c-a30b-99cb8038a1f2","order_by":2,"name":"Lazic Zoran","email":"","orcid":"","institution":"Military Medical Academy","correspondingAuthor":false,"prefix":"","firstName":"Lazic","middleName":"","lastName":"Zoran","suffix":""},{"id":519190090,"identity":"21f21ec0-7f2c-4bb7-9e44-48cd9174c529","order_by":3,"name":"Soldatovic Ivan","email":"","orcid":"","institution":"University of Belgrade","correspondingAuthor":false,"prefix":"","firstName":"Soldatovic","middleName":"","lastName":"Ivan","suffix":""},{"id":519190091,"identity":"d4edbe16-4e5d-44b3-99cc-453be93f883c","order_by":4,"name":"Markovic Aleksa","email":"","orcid":"","institution":"University of Belgrade","correspondingAuthor":false,"prefix":"","firstName":"Markovic","middleName":"","lastName":"Aleksa","suffix":""}],"badges":[],"createdAt":"2025-09-09 15:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7575328/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7575328/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":93238292,"identity":"89c7915e-2adb-4ec0-9bc6-e00af30c8d9d","added_by":"auto","created_at":"2025-10-10 14:33:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":5713,"visible":true,"origin":"","legend":"\u003cp\u003eAssessment of clinical (a) and radiographic (b, c) parameters in peri-implantitis diagnosis.\u003c/p\u003e","description":"","filename":"placeholderimage.png","url":"https://assets-eu.researchsquare.com/files/rs-7575328/v1/17bf7218ef228b17be403a9d.png"},{"id":93238294,"identity":"448b4e8e-901e-4c3f-ad2c-d51ad41b485a","added_by":"auto","created_at":"2025-10-10 14:33:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3473974,"visible":true,"origin":"","legend":"\u003cp\u003ePeri-implant infra-bony defect (a) reconstruction following implant surface decontamination by means of photodynamic therapy (b, c) and bovine bone substitute (d). Clinical and radiographic outcomes 24 months postoperatively (e, f, g).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7575328/v1/0b6cdc75289472dd9f131976.png"},{"id":93239990,"identity":"28b51961-0f2b-4e92-8c0c-0c9cb7060536","added_by":"auto","created_at":"2025-10-10 14:41:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":457324,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of mean concentration of IL-1β (a), IL-6 (b), IL-17 (c) and PPD values (95% CI) within 24 months follow-ups in test and control groups.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7575328/v1/6fe216ef327ccf565ed00ad6.png"},{"id":95528150,"identity":"ad3cb505-22e2-4dad-b28f-47c18f775ed3","added_by":"auto","created_at":"2025-11-10 10:15:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4884322,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7575328/v1/791bef54-74e3-49f8-9944-50f9dabe141e.pdf"},{"id":93238291,"identity":"800d1eaa-f70a-4900-99d3-39b99ec15042","added_by":"auto","created_at":"2025-10-10 14:33:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":77073,"visible":true,"origin":"","legend":"","description":"","filename":"Suppl..pdf","url":"https://assets-eu.researchsquare.com/files/rs-7575328/v1/18eca3530ada7c9e8d756954.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immune response to implant surface decontamination methods in the surgical peri-implantitis management","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePeri-implantitis is defined as a biofilm-mediated inflammatory condition\u0026nbsp;[1],\u0026nbsp;that, if left untreated, leads to implant loss. The host\u0026apos;s susceptibility to pathogens and released titanium particles\u0026nbsp;[2]\u0026nbsp;triggers deleterious immune-mediated host-tissue responses\u0026nbsp;[3], inducing a cascade reaction of bone-resorption-mediated interleukins (ILs)-1\u0026beta;, TNF-\u0026alpha;, IL-10, IL-6, IL-17\u0026nbsp;[4, 5]. This\u0026nbsp;results in osteoclastic differentiation and osteoclastogenesis\u0026nbsp;[6, 7],\u0026nbsp;increasing bone loss severity. Moreover, IL-17 by negative feedback maintains inflammation and supports aggressive disease progression. Therefore, understanding IL\u0026apos;s role in peri-implantitis pathogenesis could be crucial to develope effective treatment strategies to modulate the host\u0026apos;s immune response in peri-implantitis, reduce inflammation, restore tissue homeostasis, and ultimately improve clinical outcomes. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePeri-implantitis therapy was based initially on the principle of periodontitis treatment, employing mechanical methods combined with anti-inflammatory/antibacterial approaches [8]. The distinct structural features of peri-implantitis and implant surfaces as opposed to periodontitis and natural roots [9] indicate that implant surface decontamination (ISD) is an crutial step in both non-surgical and surgical therapy. ISD aims to eliminate pathogens and their products from implant surface to maintain implant biocompatibility, chemical composition, and roughness, arresting the disease progression and possibly allowing tissue regeneration [10]. Several proposed ISD methods, including mechanical (e.g. ultrasonic devices, metal curettes\u0026nbsp;[11]) and chemical (citric acid\u0026nbsp;[12]), demonstrate potential implant surface damage or alteration, increasing roughness, corrosion, and titanium particle release, and contributing to disease recurrence\u0026nbsp;[13, 14]. As a chemical agent, chlorhexidine (CHX) is one of the most widely used bisbiguanide antiseptics, available in solutions, chips and gels. In addition to its antibacterial properties, CHX demonstrated to have a dose-dependent cytotoxic effect on fibroblasts\u0026nbsp;[15-17]. However, research on CHX\u0026apos;s effect on immunomodulation\u0026nbsp;[17]\u0026nbsp;in surgical peri-implantitis treatment remains scarce. Subantimicrobial systemic antibiotic administration appears to play a host-modulating role and a notable positive short-term outcome on clinical parameters\u0026nbsp;[18], however,\u0026nbsp;antibiotics are associated with bacterial resistance and harmful side effects\u0026nbsp;[19, 20].\u0026nbsp;To address this issue, photodynamic therapy (PDT) emerges as a promising adjunctive therapy\u0026nbsp;[21]\u0026nbsp;that can immunomodulate the host response\u0026nbsp;[22]\u0026nbsp;in peri-implant tissues as an alternative to antibiotics\u0026nbsp;[23]\u0026nbsp;without altering implant surface\u0026nbsp;[14, 24, 25].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePDT\u0026apos;s working mechanism is based on binding target cells to an engaging photosensitizer (PS), activated by diode laser irradiation. Through interaction with tissue oxide, PS induces a single oxygen onset, causing a toxic effect on pathogen cells and consequently, their death\u0026nbsp;[26]. Numerous experimental\u0026nbsp;[25, 27], animal [28, 29], non-surgical [23, 30], and surgical studies [31-33]\u0026nbsp;demonstrated undeniable microbiological decontamination and partial bone formation at various implant surfaces uitlizing PDT. Nevertheless, PDT\u0026apos;s influence on bone-mediated inflammatory ILs and possible immunomodulation in reconstructive peri-implantitis treatment is still limited.\u003c/p\u003e\n\u003cp\u003eConsidering a lack of a comprehensive ISD protocol for peri-implantitis, this study aimed to determine whether different ISD methods modulate immune response, enhancing clinical and radiographic outcomes, 24 months after peri-implantitis reconstructive surgery.\u0026nbsp;\u003c/p\u003e"},{"header":"2. Material and Methods ","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.1 Study design and \u003cem\u003ePatient selection\u003c/em\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was designed based on a previously published randomised clinical trials, RCT [31], accoridng to Declaration of Helsinki of 1975, revised in 2004, and CONSORT 2010 statement. Prior to the study, the local Ethics Committee of School of Dental Medicine, University of Belgrade, approved the study (number 36/28).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEighty-one patients with peri-implantitis signs were screened and recruited from January 2014 to December 2017. Only patients meeting all eligibility criteria were enrolled in the study: Aged \u003cu\u003e\u0026gt;\u003c/u\u003e 18 years old with ability to sign inform consent; Systematically healthy or with mild or moderate well-controlled systemic conditions or diseases; No systemic antibiotic medication and anti-inflammatory drugs within the last 3 months; Presence of at least one prosthetically rehabilitated implant (bone- or tissue- level) in the function \u0026ge; 1-year with peri-implantitis signs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePeri-implantitis was defined: Peri-implant probing depth (PPD) \u0026ge; 5 mm with positive sign of bleeding on probing (BOP \u0026lsquo;\u0026rsquo;+\u0026rsquo;\u0026rsquo;) and/or suppuration at least one side around the implant, and radiographic bone lost \u003cu\u003e\u0026lt;\u003c/u\u003e 2 mm [34] (Figure 1 a, b, c).\u003c/p\u003e\n\u003cp\u003eImplant malposition, radiographic bone loss\u0026nbsp;\u0026ge; two-thirds (severe peri-implantitis) with or without implant mobility; previous surgical peri-implantitis treatment within last 6 months; heavy smoking habit (\u0026gt;10 cigarettes/day); presence of systemic diseases including diabetes mellitus, leukaemia, musculoskeletal diseases and disorders or uncontrolled systemic diseases (ASA type III); earlier head and neck radiation therapy; uses high-dosed of antiresorptive drug (i.e., bisphosphonate), immunosuppressors; pregnancy and lactation, were considered as excusion criteria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.2 Outcome variables\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eClinical and radiographic examination\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eClinical parameters including PPD, clinical attachment level (CAL), BOP, plaque index (Pi) score,\u0026nbsp;mucosal recession (MR), were measured at baseline, six, 12, and 24 months after the surgery using a graduated periodontal probe (PCPUNC 15, Hu Friedy, Chicago, USA), with 0.25 N force. Whenever required and if the periodontal probe could not reach the area around the implant, the crown was removed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAssessment of periapical radiographs were obtained from the same implants utilizing the long cone paralleling technique. Radiographic bone level (RBL) changes were estimated around the implant, measured from the prosthetic connection platform to the bottom of the defect before and at 12 and 24 months postoperatively.\u003c/p\u003e\n\u003cp\u003eClinical and radiographic examinations were performed by the two blind and calibrated periodontists (DR, ZA). To establish inter-examiner reliability, five implants with diagnosed peri-implantitis were included. The first four measurements of PPD (clinical variable) and 10 measurements of BL (radiographic variable) were repeated 24 hours apart. Calibration was accepted if inter-examiner reproducibility resulted in inter-class correlation coefficients of 0.94 (CI 95% 0.90 to 0.96, standard error (SE) 0.12) for PPD and 0.90 (CI 95% 0.89 to 0.95, standard error (SE) 0.19) for radiographic BL.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eImmunological samples and analyses\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePeri-implant crevicular fluid (PICF) samples were collected from each implant previously diagnosed with peri-implantitis [7] using standard paper strips (Periopaper, Oralflow Inc., Smithtown, NY, USA). A calibrated Periotron (Periotron\u0026reg; 6000, Interstate Drug Exchange, Amityville, NY, USA) was utilized to measure PICF volume, after which paper strips were inserted in micro-centrifuge plastic tubes and immediately stored at -70 \u0026ordm;C until further processing. Blood-contaminated strips were discharged. Samples were vortexed for 10 sec and centrifuged for 5 min at 3000 g before final analyses.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe quantitative detections of human IL-1\u0026beta;, IL-6, and IL-17A in PICFs were determined employing enzyme-linked immunosorbent assay (ELISA) using commercially available ELISA kits (Human IL-1\u0026beta; / IL-6 / IL-17A High Sensitivity ELISA, Bender MedSystems GmbH, Vienna, Austria). The assay procedure specified in the manufacturer\u0026acute;s product manual was followed for each kit to obtain optimal test performance. In brief, the absorbance of each micro-well was read on a Multiskan EX spectrophotometer (Thermo Electron Corporation, Vantaa, Finland) using 450 nm as the primary wavelength. Concentrations of ILs for each sample were assessed from standard curves by interpolation. Standard curves were generated for each tested interleukin by plotting the absorbance for each standard concentration on the Y-axis against the known standard concentration on the X-axis. Results were expressed as pg of sample/ ml of PICF volume.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003e2.3 Intervention with implant surface decontamination\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePeri-implantitis was treated surgically performing regenerative approaches to reconstruct peri-implant bone defects (PIBD) according to the procedure described earlier [31]. Briefly, two weeks before surgery, each patient underwent full-mouth non-surgical treatment and oral hygiene instruction, along with single mechanical debridement around implant diagnosed with peri-implantitis. Before ISD during the surgery, a non-transparent white envelope was used to randomise patients into one (test) group employing PDT (HELBO, Photodynamic Systems GmbH, Wels, Austria) and another contol group using CHX (Chlorhexamed\u0026reg; \u0026ndash; Direkt; GlaxoSmithKline, GmbH \u0026amp; Co. KG, Munich, Germany). In the test group, phenothiazine chloride (10 mg/mL of HELBO\u0026reg; Blue Photosensitizer), was applied onto the implant surface (3 min) and fullfilled PIBD, following saline solution irrigation and laser light exposure (180 sec/implant) (HELBO \u0026reg; TheraLite Laser, 660 nm, 100mW, total dose of 44 J/cm2) (Figure 2 a-c). In the control group, 1% CHX gel was applied directly onto the implant surface (1 min), followed by abundant saline solution irrigation (1 min). Precaution was taken to avoid contact between the bone and the CHX gel. Subsequently, PIBDs were reconstructed using bovine bone substitute and collagen membrane (Bio-Oss\u0026reg; and Bio-Gide\u0026reg;, Geistlich Pharma, AG, Wolhusen, Schweiz) (Figure 2d).\u003c/p\u003e\n\u003cp\u003eA systemic antibiotic (Amoxicillin, 500 mg or, in case of allergy, Clindamycin, 600 mg, Hemofarm, Serbia, three times per day for 5 days) was prescribed postoperatively along with oral hygiene reinforcement. Antiseptics and painkillers were not recommended during the procedure.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFollow-up controls involved supportive peri-implant care (SPIC) aiming to maintain achieved results every three months within the period of 24 months. SPIC considered oral hygiene reinforcement and mechanical plaque removal.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003e2.4 Data analyses\u0026nbsp;\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe sample size was set according to study Schwarz et al. [35] in which total BOP were reduced for 85.2 \u0026plusmn; 16.4% and 71.6 \u0026plusmn; 24.9% performing the two divers ISD methods (plastic curets and cotton pellets vs. Er:YAG laser). Using a two-sample equal-variance t-test with 80% power to reject the null hypothesis of equal means, \u0026alpha;= 0.05, with 10% drop-out rates and if SD would not exceed 15%, a total of 26 implants per group were required.\u003c/p\u003e\n\u003cp\u003eBOP\u0026nbsp;and concentrations of\u0026nbsp;IL-6, IL-17A, and IL-1\u0026beta; were considered as primary outcomes while secondary outcomes were PPD, CAL, Pi score,\u0026nbsp;MR, RBL, and patients\u0026rsquo; and implants\u0026rsquo; demographic parameters.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical analyzes were performed by using SPSS 20.0 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.) and R 3.4.2. (R Core Team (2017), R Foundation for Statistical Computing, Vienna, Austria). Results are presented as count (%), means \u0026plusmn; SD or median (25\u003csup\u003eth\u003c/sup\u003e-75\u003csup\u003eth\u0026nbsp;\u003c/sup\u003ePercentile) depending on data type and distribution. To assess correlation between variables Pearson and Spearman correlation was used. Linear mix model (LM) was emplyed to determinate the relationship between change of dependent variable and treatment adjusted for other variables.\u0026nbsp;The model used the following formula:\u0026nbsp;interleukins = group*time + group + time + clinical parameters. All \u003cem\u003ep\u003c/em\u003e values \u0026lt; 0.05 were considered significant.\u0026nbsp;\u003c/p\u003e"},{"header":"3.\tResults ","content":"\u003cp\u003eOut of 81 patients evaluated, 48 were eligible for inclusion and enrolled in the study. Four patients were excluded from further analyses (two in the control group and two in the test group) reported acute infection signs (swelling and suppuration), antibiotic intake a week before a six-month follow-up appointment, and an one patient never showed up for an appointment (CONSORT Flow Chart).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemographic and implant-based factors are presented in Table 1. No side effects and implant loss were reported at 24 months follow-up. Initial (PPD\u003cu\u003e\u0026lt;\u003c/u\u003e 5 mm) and moderated (6 \u0026lt; PPD \u003cu\u003e\u0026lt;\u003c/u\u003e 8 mm) stages of peri-implantitis (n= 52)[36] were treated in 44 patients (mean ages 58.7 \u0026plusmn; 9.4). Peri-implantitis was mostly detected in the posterior part of the mandible (63.4%), with statistically significant differences among the regions (p= 0.019).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003e3.1 Clinical, radiographi, and immunological outcomes\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA significant improvement in clinical and radiographic parameters was observed within the tested groups 12 and 24 months postoperatively (p \u0026gt; 0.05) (Table 2 a, b; Figure 2 e, f, g). BOP decreased in both groups, however, a slightly greater reduction was observed in the test group at 12 months postperatievly (p = 0.048). At 24 months, a statistically significant reduction in PPD was gained in the test compared to control group (\u0026Delta; baseline - 24 months, p = 0.043).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo statistical differences were found among groups regarding IL-17A, IL-6, and IL-1\u0026beta; concentrations prior to treatement (Table 3). Nevertheless, compared to the control group, the test group achieved significantly greater reductions in followed ILs (p \u0026lt;0.001). While ILs\u0026apos; concentrations continued to decrease significantly in the test group, a trend of ILs rising was recorded in the control group. Utilizing LM model the positive correlation was detected between clinical parameters such as PPD and ILs concentration changes (Figure 3 a, b, c). The increases in IL-1\u0026beta; were statistically related to increases in IL-6 (p = 0.046), PPD (p = 0.010), and CAL (p = 0.013). Moreover, PDT interacting with reduction of IL-1\u0026beta; was significantly related to IL-6 concentration (p= 0.007) and PPD decreases (p= 0.041), and CAL gained (p= 0.004) at 12 months postoperatively, yet without statistical differences at 24 months. Conversely, CHX interacting with a greater IL-17 concentration showed correlation with increases in terms of IL-1\u0026beta; and PPD at 12 and 24 months. No significant correlation was found between detected infra-bony defects and the following ILs.\u003c/p\u003e"},{"header":"4.\tDiscussion ","content":"\u003cp\u003eThe present RCT was conducted to evaluate the immune response induced by two diverse ISD approaches in reconstructive peri-implantitis therapy. According to the study\u0026apos;s findings, ISD of moderate implant surface roughness (75%) employing PDT, as compared to CHX application, reduced statistically significantly pro-inflammatory IL-17A, IL-1\u0026beta;, and IL-6 concentrations, associated directly with significant improvements in clinical parameters, specifically PPD, at 12 and 24 months (p = 0.036, p = 0.013). Additionally, PDT engagement was associated with greater reductions in BOP and significant increases in radiographic bone levels (p = 0.04) following surgery.\u003c/p\u003e\n\u003cp\u003eAn aggressive and rapid bone resorption in peri-impantitis is caused by a host immune response, initiated by different cell types, including T cells, which stimulate a cascade reaction of pro-inflammatory cytokines [37] such as IL-17A, IL-1\u0026beta;, and IL-6. Furthermore, implant surface features, including implant macro- and micro-topography, wettability, and hydrophilicity [12], influence immune system response during peri-implantitis. Despite the ability to influence early and rapid osseointegration, rough and modified layers of implant surfaces are prone to plaque accumulation and biofilm formation. As a result, it hinders effective microorganism removal, modifies implant surface properties, and thus alters immune responses, causing peri-implantitis. Therefore, an appropriate ISD is essential for treating peri-implantitis efficiently to arrest disease progression, allowing tissue to regenerate.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIdeally, an ISD method in peri-implantitis therapy should remove all deposits from the implant surface without affecting surface biocompatibility or integrity, while simultaneously suppressing bacteria regrowth [13], supporting immune response, and significantly influencing the re-osseointegration [10, 21]. Various mechanical and chemotherapeutic agents displayed successful clinical and radiographic outcomes [19, 38, 39] following peri-implantitis therapy, however, studies revealed greater surface alteration, changes in surface energy and wettability when these methods were utilised [12]. Consequently, this could affect a host\u0026apos;s immune response, impairing tissue regeneration. Mechanical methods, including scalers and metal curettes, showed severe damage to the implant surface, increasing roughness and bacterial adherence, and titanium (TP) particles release [2]. Some chemotherapeutic agents may damage the implant surface, causing corrosion, which, along with TP release and biofilm formation, may encourage neutrophils and macrophages to secrete pro-inflammatory cytokines directly or indirectly, inducing further bone resorption. Accordingly, photodynamic therapy, PDT, is an effective method of microorganism reduction in non-surgical peri-implantitis treatment [23], resulting in IL-17 and IL-1\u0026beta; decreases and demonstrating any alteration of zirconium or titanium surfaces \u003cem\u003ein vitro\u0026nbsp;\u003c/em\u003e[24, 25]. PDT produces reactive oxygen species (ROS), which\u0026nbsp;damage microbial cells\u0026nbsp;[40], activate cell signalling pathways, release inflammatory mediators, and modulate immune responses [41]. The eradication of peri-implantitis pathogens from different titanium surfaces was demonstrated earlier by employing PDT and regenerative surgical techniques [42-44]. Results showed a reduction in inflammation signs, including BOP and pro-inflammatory ILs, along with an enhancement of clinical parameters. This is consistent with the present study, which found a greater reduction of PPD when PDT was used for ISD compared to 1% CHX gel at 24 months following peri-implantitis surgery (\u0026Delta; baseline- 24 months, p = 0.043). Additionally, PPD interacting with PDT was positively correlated with CAL gain and IL-1\u0026beta;, IL-17A, and IL-6 decreases at 12- and 24-month postoperatively. Furthermore, BOP reduction was positively influenced by a decrease in pro-inflammatory ILs after 12 months (p = 0.048), suggesting that these ILs are crucial to determining peri-implantitis severity.\u003c/p\u003e\n\u003cp\u003eIL-1\u0026beta; behaves as a powerful stimulator of osteoclast cell differentiation and bone resorption. It was often detected in high levels along with IL-6 in patients with peri-implantitis [4, 5], similar to our findings. A synergistic effect between ILs influencing PPD changes and positive BOP was observed in our study, supporting the importance of these ILs as indicators of treatment success. Moreover, both methods applied for ISD resulted in IL-17A reduction after 6 months. Recent studies [45] demonstrated a reduction in IL-17A level, albeit without statistical significance, following open flap peri-implantitis surgery combined with ISD employing mechanical methods, saline irrigation, air polishing, and 2% chlorhexidine irrigation. Additionally, this 3-month study [45] showed a decrease in IL-1\u0026beta;, IL-6, disrupting the correlation between TNF-\u0026alpha; with IL-17A, and IL-1\u0026beta;, and significantly improving clinical outcomes. Although the above-mentioned and present studies have shown a reduction in pro-inflammatory ILs in the short term, our study reveals ILs increases at 12 and 24 months when 1% CHX gel was used for ISD. As a broad-spectrum bactericidal and bacteriostatic agent, CHX was previously utilized in peri-implantitis therapy. Nevertheless, supporting our findings, a small number of studies have failed to demonstrate CHX\u0026apos;s significance in surgical peri-implantitis treatments [46-48]. Despite the limited studies, CHX appears to alter the implant surface, affecting wettability, and exhibits cytotoxic effects on fibroblasts and mesenchymal cells [15-17]. Even so, an \u003cem\u003ein vitro\u003c/em\u003e study didn\u0026apos;t reveal that 1% CHX impaired osteoblasts [49]. The reason could be that CHX is a time-dependent agent, which implies that the short exposure time of the implant surface (1 minute) may be insufficient to harm peri-implant cells and increase ILs. However, possible differences compared to PDT could be attributed to CHX\u0026apos;s inability to eliminate pathogens and their products from the surface, leaving their biofilm remnants adherent to the surface. This could alter surface energy, inducing an immune response, decreasing osteoblast adhesion and maturation, and subsequently, disease recurrence [12, 50]. This might be an explanation for the pro-inflammatory ILs increases in this study, resulting in inflammation recurrence and bone resorption. Thus, the consequent bone resorption in the control group might be explained by the overexpression of IL-17A, which induces osteoblast precursors to generate inflammatory factors, such as IL-1\u0026beta; and IL-6, up-regulating osteoclast activity [51]. IL-17A promotes osteoclast activation and pro-inflammatory ILs release, indicating that it plays an important role in osteoclastogenesis [52], along with RANK. The fact that osteoclast activity is mediated by IL-17A concentration suggests that suppressing IL-17A may cause a decrease in IL-6 and IL-1\u0026beta;. Consequently, bone loss may be suppressed, encouraging bone formation. Accordingly, present results indicated that adjuvant PDT could decrease pro-inflammatory ILs such as IL-17A, IL-6, and IL-1\u0026beta;. Furthermore, reduction of these ILs combined with PIBD reconstruction may also influence the possibility of bone gain, potentially enhancing re-osseointegration.\u003c/p\u003e\n\u003cp\u003eThe possibility of bone formation on previously decontaminated surfaces was early demonstrated [53] determining partial re-osseointegration (59.2%) of ligature-induced peri-implantitis using PDT and guided bone regeneration (BioOss\u0026reg; and BioGide\u0026reg;)[29]. Long-term outcomes demonstrated significant bone gain with stable outcomes after ISD with PDT and PIBD reconstruction in the treatment of moderate and sever peri-implantitis [33, 54], similar to present 24-month outcomes. Another explanation for the successful results might be the exposure time to photosensitizers and laser. According to animal studies, PTD affects peri-implant pocket reduction [55] and significant bone gain [28] when more than one minute of PS is delivered to the treated area, followed by \u0026gt; 80 seconds/implant of light irradiation. Therefore, 3 minutes of PS exposure and 180 seconds of irradiation/implant combined with SPIC may explain stable clinical outcomes after 24 months. Further, low-level laser radiation stimulates cell proliferation and regeneration such as osteoblasts [56], explaining the additional bone gain following PDT. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition to the small sample size, the study limitation could be the independent ELISA analyses of ILs and the inability to assess other bone metabolism and mediators, such as TNF alpha and RANKL. This might limit the insight into the true dynamics of ILs interplay in surrounding peri-implant tissues.\u0026nbsp;\u003c/p\u003e"},{"header":"5.\tConclusion ","content":"\u003cp\u003eImplant surface decontamination utilising PDT combined with a reconstructive surgical approach could be considered an effective method for peri-implantitis management, resulting in decreased pro-inflammatory ILs and clinical and radiographic outcomes enhancement.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFounding\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was obtained for this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;study\u0026nbsp;was approved by the local Ethics Committee of School of Dental Medicine, University of Belgrade. Ethical approved number 36/28.\u003c/p\u003e\n\u003cp\u003eAffiliation: Ethics Committee of the School of Dental Medicine University of Belgrade, Belgrade, Serbia.(www.stomf.bg.ac.rs; e-mail: [email protected]).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eI\u003c/strong\u003e\u003cstrong\u003enformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003econtributions:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design.\u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eConceptualization: R.D., M. A., A.Z., L.Z.; Methodology: L.Z, R.D., M. A., A.Z.; Formal analysis and investigation: R.D., S. I; Figure prepared by: R.D., S. I; Writing - original draft preparation: R.D.; Writing - review and editing: R.D., A.Z., M.A.; Supervision: A.Z., M.A.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSchwarz, F., et al., \u003cem\u003ePeri-implantitis.\u003c/em\u003e J Periodontol, 2018. \u003cstrong\u003e89 Suppl 1\u003c/strong\u003e: p. 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Rosen, \u003cem\u003eA proposed classification for peri-implantitis.\u003c/em\u003e Int J Periodontics Restorative Dent, 2012. \u003cstrong\u003e32\u003c/strong\u003e(5): p. 533-40.\u003c/li\u003e\n\u003cli\u003eNguyen Vo, T.N., et al., \u003cem\u003eLigature induced peri-implantitis: tissue destruction and inflammatory progression in a murine model.\u003c/em\u003e Clin Oral Implants Res, 2017. \u003cstrong\u003e28\u003c/strong\u003e(2): p. 129-136.\u003c/li\u003e\n\u003cli\u003eHeitz-Mayfield, L.J., et al., \u003cem\u003eAnti-infective surgical therapy of peri-implantitis. A 12-month prospective clinical study.\u003c/em\u003e Clin Oral Implants Res, 2012. \u003cstrong\u003e23\u003c/strong\u003e(2): p. 205-10.\u003c/li\u003e\n\u003cli\u003eIrshad, M., et al., \u003cem\u003eEffects of Implant Surface Debridement and Systemic Antibiotics on the Clinical and Microbiological Variables of Periimplantitis.\u003c/em\u003e Biomed Res Int, 2021. \u003cstrong\u003e2021\u003c/strong\u003e: p. 6660052.\u003c/li\u003e\n\u003cli\u003eCai, Z., et al., \u003cem\u003eAntimicrobial effects of photodynamic therapy with antiseptics on Staphylococcus aureus biofilm on titanium surface.\u003c/em\u003e Photodiagnosis Photodyn Ther, 2019. \u003cstrong\u003e25\u003c/strong\u003e: p. 382-388.\u003c/li\u003e\n\u003cli\u003eAebisher, D., P. Woźnicki, and D. Bartusik-Aebisher, \u003cem\u003ePhotodynamic Therapy and Adaptive Immunity Induced by Reactive Oxygen Species: Recent Reports.\u003c/em\u003e Cancers, 2024. \u003cstrong\u003e16\u003c/strong\u003e(5): p. 967.\u003c/li\u003e\n\u003cli\u003eHaas, R., et al., \u003cem\u003eElimination of bacteria on different implant surfaces through photosensitization and soft laser. An in vitro study.\u003c/em\u003e Clin Oral Implants Res, 1997. \u003cstrong\u003e8\u003c/strong\u003e(4): p. 249-54.\u003c/li\u003e\n\u003cli\u003eDortbudak, O., et al., \u003cem\u003eLethal photosensitization for decontamination of implant surfaces in the treatment of peri-implantitis.\u003c/em\u003e Clin Oral Implants Res, 2001. \u003cstrong\u003e12\u003c/strong\u003e(2): p. 104-8.\u003c/li\u003e\n\u003cli\u003eRaka\u0026scaron;ević, D. and D. Gabrić, \u003cem\u003eThe Effect of Implant Surface Design and Their Decontamination Methods in Peri-Implantitis Treatment\u003c/em\u003e, in \u003cem\u003eCurrent Concepts in Dental Implantology\u003c/em\u003e, G. Dragana and V. Marko, Editors. 2021, IntechOpen: Rijeka. p. Ch. 12.\u003c/li\u003e\n\u003cli\u003eGon\u0026ccedil;alves, L., et al., \u003cem\u003eThe Effect of Peri-Implant Therapy on the Expression of Th17-Related Cytokines in Patients with Peri-Implant Mucositis and Peri-Implantitis: A Prospective Longitudinal Study.\u003c/em\u003e J Clin Med, 2025. \u003cstrong\u003e14\u003c/strong\u003e(2).\u003c/li\u003e\n\u003cli\u003ede Waal, Y.C., et al., \u003cem\u003eImplant decontamination with 2% chlorhexidine during surgical peri-implantitis treatment: a randomized, double-blind, controlled trial.\u003c/em\u003e Clin Oral Implants Res, 2015. \u003cstrong\u003e26\u003c/strong\u003e(9): p. 1015-23.\u003c/li\u003e\n\u003cli\u003eWilensky, A., et al., \u003cem\u003eThe efficacy of implant surface decontamination using chemicals during surgical treatment of peri-implantitis: A systematic review and meta-analysis.\u003c/em\u003e J Clin Periodontol, 2023. \u003cstrong\u003e50 Suppl 26\u003c/strong\u003e: p. 336-358.\u003c/li\u003e\n\u003cli\u003eRoccuzzo, M., et al., \u003cem\u003eSurgical therapy of peri-implantitis lesions by means of a bovine-derived xenograft: comparative results of a prospective study on two different implant surfaces.\u003c/em\u003e J Clin Periodontol, 2011. \u003cstrong\u003e38\u003c/strong\u003e(8): p. 738-45.\u003c/li\u003e\n\u003cli\u003eVerdugo, F., et al., \u003cem\u003eBone microbial decontamination agents in osseous grafting: an in vitro study with fresh human explants.\u003c/em\u003e J Periodontol, 2011. \u003cstrong\u003e82\u003c/strong\u003e(6): p. 863-71.\u003c/li\u003e\n\u003cli\u003eLee, B.S., et al., \u003cem\u003eSurface property alterations and osteoblast attachment to contaminated titanium surfaces after different surface treatments: An in vitro study.\u003c/em\u003e Clin Implant Dent Relat Res, 2018. \u003cstrong\u003e20\u003c/strong\u003e(4): p. 583-591.\u003c/li\u003e\n\u003cli\u003eVan bezooijen, R.L., et al., \u003cem\u003eInterleukin-17: A new bone acting cytokine in vitro.\u003c/em\u003e J Bone Miner Res, 1999. \u003cstrong\u003e14\u003c/strong\u003e(9): p. 1513-21.\u003c/li\u003e\n\u003cli\u003eLee, Y., \u003cem\u003eThe role of interleukin-17 in bone metabolism and inflammatory skeletal diseases\u003c/em\u003e, in \u003cem\u003eBMB Rep\u003c/em\u003e. 2013. p. 479-83.\u003c/li\u003e\n\u003cli\u003eRenvert, S., I. Polyzois, and R. Maguire, \u003cem\u003eRe-osseointegration on previously contaminated surfaces: a systematic review.\u003c/em\u003e Clin Oral Implants Res, 2009. \u003cstrong\u003e20 Suppl 4\u003c/strong\u003e: p. 216-27.\u003c/li\u003e\n\u003cli\u003eEtemadi, A., H. Sabri, and M. Enssi, \u003cem\u003eSurgical reconstruction of peri-implantitis with adjunctive antimicrobial photodynamic therapy: A case report with 5-year follow-up.\u003c/em\u003e Clin Adv Periodontics, 2024. \u003cstrong\u003e14\u003c/strong\u003e(3): p. 185-191.\u003c/li\u003e\n\u003cli\u003eMadi, M. and A.S. Alagl, \u003cem\u003eThe Effect of Different Implant Surfaces and Photodynamic Therapy on Periodontopathic Bacteria Using TaqMan PCR Assay following Peri-Implantitis Treatment in Dog Model.\u003c/em\u003e Biomed Res Int, 2018. \u003cstrong\u003e2018\u003c/strong\u003e: p. 7570105.\u003c/li\u003e\n\u003cli\u003eMiranda, J.M., et al., \u003cem\u003ePhotobiomodulation Therapy in the Proliferation and Differentiation of Human Umbilical Cord Mesenchymal Stem Cells: An In Vitro Study.\u003c/em\u003e J Lasers Med Sci, 2020. \u003cstrong\u003e11\u003c/strong\u003e(4): p. 469-474.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Socio-demographic, restorative, and implant-based variables at baseline\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTest group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e58.7 \u0026plusmn; 9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e18 (82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e16 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e34 (77.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e6 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e10 (22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeriod of implant loading, (years, mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e7.01\u0026plusmn;3.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistory of treated periodontitis, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e14 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e16 (72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e30 (65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.335\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e8 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e6 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e14 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmokers (\u003cu\u003e\u0026lt;\u003c/u\u003e 10 cigarettes), N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e3 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.987\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of treated implants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.213\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocation, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eMaxilla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e7 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e6 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e13 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.866\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eMandible\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e19 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e20 (76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e39 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegion, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003ePremolar\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e8 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e11 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e19 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.019*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eMolar\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e18 (69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e15 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e33 (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImplant surface, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eMTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e3 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e7 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eOssteospead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e5 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e6 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e11 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eTiUnite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e11 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e10 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e21 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eBCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e6 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e7 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e13 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurface roughness,\u0026nbsp;n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eModerate\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e20 (77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e19 (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e39 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.689\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eSmooth\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e6 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e7 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e13 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of restoration, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eSingle crown, cement-retained\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e15 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e13 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e28 (54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003ePartial or full-arch bridge, cement-retained\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e7 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e9 (35) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e16 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eImplant-supported prosthesis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e4 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e8 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOsseous defects, n (%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eClass 1 b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e9 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e12 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e21 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.177\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eClass 1 d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e9 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e8 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e17 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003eClass 1 e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e8 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e6 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e14 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePPD, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 5 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e15 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e15 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e30 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.278\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 6 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e11 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e11 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e22 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026gt; 8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRBL at mesial site, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 2 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e9 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e7 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e16 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 3 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e13 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e14 (54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e27 (52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cu\u003e\u0026gt;\u003c/u\u003e 4 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e5 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e9 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRBL at distal site, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 2 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e11 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e12 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e23 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.683\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 3 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e10 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e10 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e20 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e 4 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e5 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e4 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e9 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003csup\u003e\u0026dagger;\u0026nbsp;\u003c/sup\u003en- number of implant diagnosed with peri-implantitis presented in percentages (%) ; N- number of subject with peri-implantitis presented in percentages.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026Dagger;\u0026nbsp;\u003c/sup\u003eMTX- Acid washed surface, (Zimmer Biomet Dental, Carlsbad, CA, USA); TiUnite- Porous anodized surface (Nobel BioCare, Gothenburg, Swede); Osseospeed- Fluoride-modified titanium dioxide grit-blasted (AstraTech, Mölndal, Sweden), BCT- Machined polished implant surface (BCT Implant System, SCG, Serbia); PPD- distribution of peri-implant probing depth presented in millimetres before any treatment; RBL- distribution of marginal bone loss (peri-implantits severity[34]) based on radiographic analyses presented in millimetres before treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e*Statistically significant differences in changes (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt;\u003cem\u003e\u0026nbsp;\u003c/em\u003e0.05). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2a.\u003c/strong\u003e Clinical outcomes variables on implants level at baseline, and six, 12, and 24 months after the surgical procedure.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTest group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;(n = 26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;(n = 26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePPD, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e5.38 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e5.41 \u0026plusmn; 1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.378\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.52 \u0026plusmn; 0.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.94 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.257\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.50 \u0026plusmn; 0.55*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e3.06 \u0026plusmn; 1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.036 \u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.88 \u0026plusmn; 0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.35 \u0026plusmn; 1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.32 \u0026plusmn; 0.42*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e3.01 \u0026plusmn; 1.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.013 \u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.96 \u0026plusmn; 0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.4 \u0026plusmn; 0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.043 \u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAL, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e5.17 \u0026plusmn; 1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e5.27 \u0026plusmn; 1.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.367\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.56 \u0026plusmn; 1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.89\u0026nbsp;\u0026plusmn; 0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.225\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.52 \u0026plusmn; 0.97*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.97 \u0026plusmn; 1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2. 65\u0026nbsp;\u0026plusmn; 1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.29\u0026nbsp;\u0026plusmn; 1.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.43 \u0026plusmn; 0.91*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.95 \u0026plusmn; 1.2*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e2.74\u0026nbsp;\u0026plusmn; 1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e2.32\u0026nbsp;\u0026plusmn; 1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMR, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.74 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.69 \u0026plusmn; 0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.476\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.58 \u0026plusmn; 0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.56 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.612\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.54 \u0026plusmn; 0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.53 \u0026plusmn; 0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.463\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.2\u0026nbsp;\u0026plusmn; 0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.16\u0026nbsp;\u0026plusmn; 0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.54 \u0026plusmn; 0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.57 \u0026plusmn; 0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.2\u0026nbsp;\u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.12\u0026nbsp;\u0026plusmn; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.077\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBOP, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e86 \u0026plusmn; 19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e83.94 \u0026plusmn; 26.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.761\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.2 \u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e0.62 \u0026plusmn; 3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.336\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.67 \u0026plusmn; 3.33*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e6.17 \u0026plusmn; 15.4*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.048 **\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e85.33 \u0026plusmn; 18.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e77.76 \u0026plusmn; 26.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.445\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e4.67 \u0026plusmn; 9.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e8.02 \u0026plusmn; 12.55*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e81.33 \u0026plusmn; 24.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e75.91 \u0026plusmn; 36.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.413\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePi, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e96.7 \u0026plusmn; 6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e85.18 \u0026plusmn; 23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e10.67 \u0026plusmn; 17.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e17.28 \u0026plusmn; 11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e7.3 \u0026plusmn; 11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e14.8 \u0026plusmn; 20.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.286\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e89.33 \u0026plusmn; 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e70.30 \u0026plusmn; 2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.004 **\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e8.4 \u0026plusmn; 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e14.2 \u0026plusmn; 12.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.006 **\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e88.3 \u0026plusmn; 2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e71 \u0026plusmn; 10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.001 **\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026sect;\u0026nbsp;\u003c/sup\u003eSD, standard deviation;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026para;\u003c/sup\u003e PPD, peri-implant probing depth; CAL, clinical attachment level; MR, mucosal recession; BOP, bleeding on probing; Pi, Plaque index score; PPD, CAL, MR expressed in mm; BOP and Pi expressed as percentage.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e* Time-related within-group statistically significant difference baseline vs 12 months; baseline vs 24 months; p\u0026lt; 0.001; analyzed by t test or Wilcoxon Signed-Rank test;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e** Statistically significant difference between the groups by t test or Mann-Whitney Test (p \u0026lt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2b.\u003c/strong\u003e Radiographic bone level, RBL changes assessed on implants level at baseline, and 12 and 24 months after the surgical procedure.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTest group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;(n = 26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; (n = 26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRBL, mesial side, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.21 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.33 \u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.662\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.4 \u0026plusmn; 0.21*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.6 \u0026plusmn; 0.46*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.029 \u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026Delta; baseline - 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.81 \u0026plusmn; 0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.73 \u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.405\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.6 \u0026plusmn; 0.24*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;1.1 \u0026plusmn; 0.42*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt; 0.001 \u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.61 \u0026plusmn; 0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.23 \u0026plusmn; 0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.117\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRBL, distal side, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.2 \u0026plusmn; 0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.1 \u0026plusmn; 0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.667\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.3 \u0026plusmn; 0.23*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.61 \u0026plusmn; 0.3*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.041 \u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026Delta; baseline - 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.97 \u0026plusmn; 0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.5 \u0026plusmn; 0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.043 \u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.3 \u0026plusmn; 0.22*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;0.7 \u0026plusmn; 0.31*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.786\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.98 \u0026plusmn; 0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.41 \u0026plusmn; 0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.045 \u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026sect;\u0026nbsp;\u003c/sup\u003eSD, standard deviation;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e* Time-related within-group statistically significant difference baseline vs 12 months; baseline vs 24 months; p\u0026lt; 0.001; analyzed by t test or Wilcoxon Signed-Rank test;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e** Statistically significant difference between the groups by t test or Mann-Whitney Test (p \u0026lt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Immunological outcomes measured and their changes among baseline, six, 12 and 24 months after the surgery.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"554\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTest group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;(n = 26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;(n = 26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-6\u003c/strong\u003e\u003cstrong\u003e, mean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.56 \u0026plusmn; 0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.86 \u0026plusmn; 0.991\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.456\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.27 \u0026plusmn; 0.2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.59 \u0026plusmn; 0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.046**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.14 \u0026plusmn; 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.01 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.004**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026Delta; baseline -12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.42 \u0026plusmn; 0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.15 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.23 \u0026plusmn; 0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.73 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.006**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.33 \u0026plusmn; 0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.13 \u0026plusmn; 0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e\u0026beta;,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003emean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e75.32 \u0026plusmn; 39.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e93.72 \u0026plusmn; 39.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26.43 \u0026plusmn; 7.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e59.5 \u0026plusmn; 30.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.21 \u0026plusmn; 17.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e80.59 \u0026plusmn; 51.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026Delta; baseline -12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e45.11 \u0026plusmn; 36.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13.124 \u0026plusmn; 45.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e28.42 \u0026plusmn; 20.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e88.37 \u0026plusmn; 55.43\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e46.9 \u0026plusmn; 41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.35 \u0026plusmn; 48.28\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-17A,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003emean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ebaseline\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.26 \u0026plusmn; 1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.31 \u0026plusmn; 1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.921\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.66 \u0026plusmn; 1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.61 \u0026plusmn; 1.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.012**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.98 \u0026plusmn; 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.47 \u0026plusmn; 1.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.002**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026Delta; baseline -12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.3 \u0026plusmn; 1.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.16 \u0026plusmn; 1.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.93 \u0026plusmn; 1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.61 \u0026plusmn; 2.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.007**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026Delta; baseline - 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.33 \u0026plusmn; 1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.29 \u0026plusmn; 2.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026sect;\u0026nbsp;\u003c/sup\u003eSD, standard deviation;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e* Time-related within-group statistically significant difference baseline vs 12 months; baseline vs 24 months; p\u0026lt; 0.001; analyzed by t test or Wilcoxon Signed-Rank test;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e** Statistically significant difference between the groups by t test or Mann-Whitney Test (p \u0026lt; 0.05).\u0026nbsp;\u003c/p\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":"peri-implantitis, photodynamic therapy, implant surface decontamination, pro-inflammatory interleukin, reconstructive therapy","lastPublishedDoi":"10.21203/rs.3.rs-7575328/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7575328/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e The study assessed the efficacy of different implant surface decontamination methods in surgical peri-implantitis (PI) treatment, considering the immune response.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterial and Methods:\u003c/strong\u003e Forty-four patients (aged 58.7 ± 9.4) dignosed with 52 peri-implantitis (peri-implant probing depth, (PPD) \u0026gt; 5 mm, bleeding on probing (BOP “+”), and bone loss \u0026gt; 2 mm) completed a two-year study. ISD was employed by either photodynamic therapy (PDT, test group) or 1% chlorhexidine di-gluconate gel (control group) followed by peri-implant bone defects reconstruction. Interleukins (IL) 17A, IL-1β, and IL-6 concentrations, clinical and radiographic outcomes were assessed throughout 24 months postoperatively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e IL-17A, IL-1β, and IL-6 concentrations were significantly reduced 24 months postoperatievly (p = 0.007, p \u0026lt; 0.001, and p = 0.006) in the test group compared to the control one. A statistically significant decrease in terms of PPD was achieved in the test compared to the control group at 12 and 24 months postoperatively (p= 0.036, p= 0.043).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e PDT may provide a feasible method for implant surface decontamination, improving immune response in reconstructive peri-implantitis treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical relevance:\u003c/strong\u003eA reconstructive peri-implantitis surgery combined with PDT effectively decreases pro-inflammatory interleukin during the first 24 months postoperatively, significantly enhancing clinical and radiographic outcomes.\u003c/p\u003e\n\u003cp\u003eStudy was registered retrospectively at ClinicalTrials.com (NCT05187663).\u003c/p\u003e","manuscriptTitle":"Immune response to implant surface decontamination methods in the surgical peri-implantitis management","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-10 14:33:08","doi":"10.21203/rs.3.rs-7575328/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":"4c91dc23-30a9-4444-8862-b2e08f56ed93","owner":[],"postedDate":"October 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-09T22:23:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-10 14:33:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7575328","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7575328","identity":"rs-7575328","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}