The Effects of Fixed Space Maintainers Luted with Resin Cement on Interleukin-18 Levels in Gingival Crevicular Fluid

The Effects of Fixed Space Maintainers Luted with Resin Cement on Interleukin-18 Levels in Gingival Crevicular Fluid | 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 Article The Effects of Fixed Space Maintainers Luted with Resin Cement on Interleukin-18 Levels in Gingival Crevicular Fluid Suat Serhan Altıntepe Dogan, Ozgur Dogan, Esra Nur Akgul, Ayhan Vurmaz This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8793963/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract The aim of this study was to compare periodontal parameters and IL-18 (Interleukin-18) levels in gingival crevicular fluid (GCF) following fixed space maintainers (FSMs) luted with resin cement (RC) versus glass ionomer cement (GIC) in children. This split-mouth study was conducted in 31 children aged 6 to 10 years who received FSMs after premature loss of mandibular second primary molars. Left mandibular first molars were luted with self-adhesive RC and right molars with conventional GIC. Gingival Index (GI), Plaque Index (PI), and Periodontal Probing Depth (PPD) were recorded at baseline and 1 week follow-up. GCF was collected from the teeth using Periopaper® strips before luting and at the one-week follow-up and IL-18 levels were measured with ELISA. Mann-Whitney U test was used for intergroup comparisons, and Wilcoxon Signed Ranks test for intragroup comparisons. Pre- and post-luting differences were analyzed, revealing no significant distinctions between the right and left sides across the PI, GI, and PPD parameters (p > 0.05). In the RC group, IL-18 measurements taken at two different intervals showed a significant difference (p = 0.036). RC-luted FSMs showed increased IL-18, suggesting a heightened inflammatory response, possibly related to RC components. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Fixed Space Maintainer IL-18 Glass Ionomer Cement Resin Cement Gingival Inflammation Figures Figure 1 Figure 2 Figure 3 Introduction Fixed space maintainers (FSMs) are important preventive orthodontic devices used in pediatric dentistry. These devices are specifically designed to preserve the spaces left by premature tooth loss or planned tooth extractions. Maintaining these spaces is crucial for guiding the proper eruption of permanent teeth, contributing to a child’s healthy dental development 1 , 2 . Pediatric dentists are the most frequently consulted professionals during this stage, and their preventive practices significantly impact the preservation of the edentulous space during the transition from mixed dentition to permanent dentition 3 , 4 . FSMs need to remain cemented in the mouth for an extended period, as even a matter of days can be significant in this process. To achieve optimal results, the cementation process must be conducted with durable luting cement. Traditionally, it has been advised to cement FSMs using conventional glass ionomer cement (GIC) 5 , 6 . However, over the past decade, resin cement (RC) has become increasingly prevalent 7 – 9 due to significant advancements in bonding technology and the rising adoption of adhesive resin cement within dentistry 10 – 12 . While RC has been adopted to potentially improve the longevity of FSMs, concerns arise regarding the possibility of residual luting cement extending into the gingival sulcus. Such remnants may contribute to periodontal inflammation, yet research examining this issue in pediatric patients remains limited. To better understand the biological implications of cement remnants, gingival crevicular fluid (GCF) serves as the primary medium for analyzing alterations in the local tissue environment, thereby facilitating the assessment of periodontal health and disease. This fluid is instrumental in understanding the physiological changes occurring in periodontal conditions. The noninvasive collection of biomarkers in GCF is an essential diagnostic method for accurately assessing gingival health in clinical practice 13 . Numerous inflammatory cytokine biomarkers indicate the presence of gingival inflammation. Pro-inflammatory cytokines, tumor necrosis factor (TNF-α), anti-inflammatory cytokines, and matrix metalloproteinases play significant roles in regulating inflammatory responses 13 , 14 . Among these biomarkers, interleukin-18 (IL-18) is a significant pro-inflammatory cytokine belonging to the interleukin-1 (IL-1) family. It is essential in the immune response to infections and various diseases 15 . The function of IL-18 in the inflammatory response is to facilitate the expression of adhesion molecules on endothelial cells, thereby increasing the recruitment of immune cells to the site of inflammation. The accumulation of IL-18 in regions that are persistently exposed to irritants triggers chronic tissue damage, facilitating the progression of the disease's pathogenesis 16 . The role of IL-18 in immune regulation and inflammation suggests that it may serve as a potential biomarker for tracking the progression of various diseases 16 , 17 . Studies have indicated that the expression levels of IL-18 are significantly elevated in gingival crevicular fluid and gingival tissue samples associated with gingival inflammation and periodontal diseases 16 , 18 , 19 . Given these considerations, it is important to re-evaluate FSM cementation protocols, particularly when RC is used in areas close to the gingival pocket. However, current literature remains unclear about inflammation effects in the periodontal sulcus caused by using resin cement for luting space maintainers. The null hypothesis of this study states that FSMs luted with conventional GIC and those luted with resin cement result in similar alterations in IL-18 levels within the GCF of pediatric patients. Methods Study Design This study was designed as a non-randomized split-mouth clinical trial that was conducted at Afyonkarahisar Health Sciences University, Faculty of Dentistry, Department of Pediatric Dentistry clinic between June 2022 and June 2023. This study protocol was initiated following approval from the Ethics Committee of the Faculty of Medicine, Afyonkarahisar Health Sciences University (reference number: 2022/7/336), and all procedures were carried out in accordance with the ethical standards outlined in the Declaration of Helsinki. The protocol was retrospectively registered at ClinicalTrials.gov (Identifier: NCT06811597; registration date: 06 February 2025). Comprehensive information was provided to all participants and parents regarding the importance of oral hygiene maintenance. Measures were taken to ensure that optimal oral hygiene standards were upheld throughout the study. This study was conducted under the Consolidated Standards of Reporting Trials (CONSORT) guidelines (Fig. 1) and ethical principles for medical research involving human subjects as outlined in the Declaration of Helsinki. All patients provided informed consent by signing a consent form. Sample Size Given the scarcity of identical studies in the existing literature, the sample size calculation was based on an established effect size. The effect size was determined to be 0.55 for the difference in IL levels measured on the first and seventh days following the application of FSM bonding material to either the right or left side of the jaw. Using a paired t-test with a statistical power of 0.80, the minimum required sample size was calculated to be twenty-eight participants. To account for a potential 10% dropout rate, thirty-six participants were initially enrolled. The study ultimately concluded with thirty-one participants. Eligibility Criteria Inclusion Criteria Children who do not have any underlying systemic diseases. Children have not received any antibiotic treatment in the past four months. Both girls and boys between the ages of 6 and 10. The second primary molar teeth (75 and 85) were extracted from patients due to caries and associated periapical pathologies. Existence of the antagonistic tooth of the abutment tooth. Children and their parents willing to participate in the study and attend one week follow-up were included. Exclusion Criteria Children present with periodontal disease. Children with cognitive disabilities. Children with skeletal or dental malocclusion. Children and their parents who did not meet the specified criteria were excluded from the study. Clinical Procedures The patients who elected to undergo FSM treatment had previously visited the pediatric dentistry clinic at which their teeth, numbered 75 and 85, were extracted due to carious lesions and periapical pathologies. The extractions were performed at one-week intervals. This procedure was conducted utilizing behavioral guidance techniques while the patient was seated in the dental chair at the clinic. Following each tooth extraction, a week was designated for the healing of the extraction site. Subsequently, an appointment was scheduled for the following week to obtain impressions for the space maintainer. The study examined various factors, including the patient’s age, gender, Plaque index (PI), Gingival Index (GI), and Periodontal Probing Depth (PPD). All measurements were conducted utilizing a Williams periodontal probe (122-006, HuFriedy, Chicago, IL, USA) on the multiple surfaces of each tooth: mesiobuccal, buccal, distobuccal, distolingual, lingual, and mesiolingual 20 . The GI scores 21 , which range from 0 to 3, were determined by aggregating the scores from the buccal, lingual, mesial, and distal surfaces of each tooth. This total was then divided by four to yield an average score, where a value of 0 signifies healthy gingival conditions and a score of 3 denotes severe inflammation of the gums characterized by spontaneous bleeding. The PI scores [21] for each tooth were computed on a scale of 0 to 3, derived from the scores assigned to the buccal, lingual, mesial, and distal surfaces. A score of 0 indicates the absence of visible plaque, while a score of 3 denotes severe plaque accumulation. The cumulative score for each tooth was then averaged by dividing the total by four. Orthodontic bands (Morelli, Alameda Jundiaí, 230/250, Sorocaba 18085-090, Sao Paulo, Brazil) corresponding to the identified tooth numbers were promptly selected and fitted on the same day. The loop component was shaped and contoured to align with the dental arch and then soldered into place. The bands were polished using a periodontal polishing rubber without polishing paste. Before luting the FSMs, GCF samples were collected from the mid-buccal area of the targeted teeth using Periopaper (Periopaper®, Proflow Inc. Amityville, NY, USA). The strips were carefully placed into the gingival sulcus or periodontal pocket until slight resistance was felt and retained for 1 minute 22 . Contaminated or unsuitable periopapers were discarded, and a new sample was obtained if necessary. All collected Periopaper strips were pooled in Eppendorf tubes (Eppendorf®, Eppendorf AG, Hamburg, Germany) containing 40 μL of 1% Bovine Serum Albumin solution in phosphate-buffered saline (pH:7.4) with Tween, centrifuged at 12,000 g for 5 minutes at 4 ºC and stored at −80 °C in an Ultra Low-Temperature Freezer (Qingdao Carebios Biological Technology Co. Shandong., China) until they were required for laboratory analysis. A split-mouth design was used to minimize inter-individual variability. However, allocation was not randomized. The luting materials were predetermined as follows: Resin cement (RC) was applied to the left mandibular first permanent molar (tooth 36). Glass ionomer cement (GIC) was applied to the right mandibular first permanent molar (tooth 46). This fixed allocation was implemented to standardize clinical procedures across participants. All clinical procedures were performed by the same pediatric dentist to minimize operator variability. After the procedure, patients were instructed to refrain from all oral intake for the initial 30 minutes post-procedure and to avoid chewing hard foods for a subsequent 24-hour period. The patients were once more advised regarding the importance of oral hygiene education. After the initial evaluation, periodontal parameters were reassessed in the patients scheduled for follow-up one week later. Additionally, a GCF sample was recollected from the same site for analysis. ELISA assays were conducted to quantify IL-18 levels in GCF samples. After the implementation of these protocols, patients were advised to schedule their regular follow-up examinations (Fig. 2). Figure 2. An illustration of the patient included in the study. (A) Baseline intraoral photograph presented prior to the procedure. (B) The GCF sample immediately before the luting process. (C) Acquisition of the GCF sample during the one-week follow-up session post-luting. (D) In certain instances, GCF samples were obtained from a site approved by the FSM due to insufficient GCF volume being collected initially. IL-18 Measurement The assays were conducted employing human-specific IL-18 ELISA kits sourced (Elabscience Biotechnology, Houston, TX, 77079, USA). The procedures were carried out following the manufacturer's specifications and protocols. Eppendorf tubes containing periopapers were equilibrated to room temperature for 20 minutes after the thawing process. The samples were then incubated on a rocking platform overnight at 4 °C. The concentrations of IL-18 in the GCF samples were quantitatively assessed using a commercially available enzyme-linked immunosorbent assay (ELISA) format on a Chemwell 2910 Microplate Spectrophotometer (Awareness Technology Inc., Palm City, USA). The assays were performed in 96-well plates (ISOLAB, Laborgerate GmbH, Istanbul, Türkiye). Standardized concentration curves and corresponding absorbance values were employed to quantify the IL-18 levels in patient samples, expressed in picograms per milliliter (pg/mL). Statistical Analysis Data analysis was conducted using SPSS version 24.0 (Statistical Package for the Social Sciences, IBM, NY, USA). Descriptive statistics for quantitative variables were reported as mean ± standard deviation and median (range: minimum-maximum). Both mean ± standard deviation and median (minimum-maximum) were utilized to describe quantitative variables. The Mann-Whitney U test was employed to assess differences between two categories of qualitative variables for the quantitative variable, given the violation of normal distribution assumptions. The Wilcoxon Signed Ranks test was used to evaluate differences between two dependent quantitative variables due to normality violations. The results were evaluated at the p <0.05 significance level. Results Upon analyzing the changes in PI measurements before and after the luting of space maintainers, only the variations observed in teeth 36 and 46 were statistically significant (p=0.002). The PI values recorded from the teeth designated for the luting of the fixed space maintainers showed a statistically significant increase in comparison to the PI values obtained during the control sessions within the first week (Table 1). In the scope of statistical analysis, we evaluated pre- and post-intervention differences and investigated whether there were statistically significant distinctions between the right and left sides regarding these differences. Our results demonstrated no significant difference across all evaluated parameters between the right and left sides (p>0.05) (Table 1). Index Tooth Time Avg.±SD Median (Min-Max) p value GI Right (46) Before Luting 0.46±0.43 0.33 (0.00-1.66) 0.104 a After Luting 0.30±0.34 0.33 (0.00-1.33 Left (36) Before Luting 0.40±0.35 0.33 (0.00-1.33) 0.741 a After Luting 0.39±0.38 0.33 (0.00-1.66) Right (46) Difference for Tooth 46 -0.16±0.51 0.00 (-1.33-0.67) 0.311 b Left (36) Difference for Tooth 36 -0.01±0.47 0.00 (-1.17-1.00) Right (84) Before Luting 0.20±0.33 0.00 (0.00-1.16) 0.909 a After Luting 0.20±0.27 0.00 (0.00-1.00) Left (74) Before Luting 0.30±0.35 0.33 (0.00-1.33) 0.842 a After Luting 0.28±0.36 0.16 (0.00-1.33) Right (84) Difference for Tooth 84 0.00±0.34 0.00 (-1.16-1.00) 0.964 b Left (74) Difference for Tooth 74 -0.02±0.39 0.00 (-1.17-1.17) PI Right (46) Before Luting 0.71±0.46 0.66 (0.00-2.00) 0.002 a After Luting 0.40±0.37 0.33 (0.00-1.16) Left (36) Before Luting 0.63±0.45 0.66 (0.00-2.00) 0.144 a After Luting 0.47±0.48 0.33 (0.00-2.00) Right Difference for Tooth 46 -0.31±0.51 -0.16 (-1.84-0.50) 0.485 b Left Difference for Tooth 36 -0.16±0.69 -0.17 (-1.67-1.67) Right (84) Before Luting 0.45±0.36 0.33 (0.00-1.33) 0.126 a After Luting 0.58±0.47 0.66 (0.00-2.00) Left (74) Before Luting 0.64±0.41 0.66 (0.00-1.33) 0.370 a After Luting 0.58±0.48 0.50 (0.00-2.00) Right (84) Difference for Tooth 84 0.13±0.51 0.00 (-1.00-1.67) 0.228 b Left (74) Difference for Tooth 74 -0.06±0.43 0.00 (-1.00-1.00) PPD Right (46) Before Luting 1.28±0.33 1.16 (1.00-2.16) 0.497 a After Luting 1.33±0.41 1.16 (1.00-2.50) Left (36) Before Luting 1.33±0.39 1.16 (1.00-2.50) 0.192 a After Luting 1.44±0.48 1.33 (1.00-2.66) Right (46) Difference for Tooth 46 0.05±0.29 0.00 (-0.50-0.84) 0.352 b Left (36) Difference for Tooth 36 0.11±0.39 0.00 (-0.50-1.17) Right (84) Before Luting 1.08±0.16 1.00 (1.00-1.66) 0.686 a After Luting 1.09±0.14 1.00 (1.00-1.50) Left (74) Before Luting 1.06±0.12 1.00 (1.00-1.50) 0.137 a After Luting 1.10±0.12 1.00 (1.00-1.33) Right (84) Difference for Tooth 84 0.01±0.18 0.00 (-0.50-0.34) 0.440 b Left (74) Difference for Tooth 74 0.04±0.16 0.00 (-0.50-0.33) GI: Gingival Index, PI: Plaque Index, PPD: Periodontal Probing Depth, AVG:Average, SD:Standard Deviation, Min:Minimum, Max:Maximum, a: Wilcoxon Signed Rank test, b: Mann-Whitney U test Table 1. Variations in periodontal indices were observed over the duration of the one-week study. Intragroup Comparisons Upon conducting an analysis of the variations in IL-18 levels, a statistically significant difference in IL-18 production was observed when utilizing conventional GIC for luting in the right teeth (p=0.046). In the RC group, the IL-18 measurements recorded at two distinct time intervals for luting the teeth on the left side showed a significant difference (p=0.036). When IL-18 averages from the pre-luting phase and the first-week control session were compared, a statistically significant increase in IL-18 levels was observed. The changes in IL-18 levels over time are illustrated in Fig. 3. Intergroup Comparisons Table 2 presents a comparative analysis of IL-18 levels between the two groups, highlighting the measurements taken before, after, and the changes between these time points for each group. Significant differences were detected in the measurements taken after luting and the comparisons conducted before/after differences (p<0.001 and p=0.003, respectively). Before the luting, the average IL-18 levels in the GIC group were recorded at 132.54 ± 100.53 pg/mL, whereas in the RC group, the average was higher at 157.85 ± 113.50 pg/mL. At the after-luting time point, the mean IL-18 concentration was observed to be 89.63 ± 70.07 pg/mL in the GIC group, whereas, in the RC group, the mean IL-18 level was significantly higher at 198.77 ± 138.67 pg/mL. A decrease was observed in the GIC group between the before/after times, and an increase was observed in the RC group. IL-18 GIC RC p value Mean±SD Median (Min-Max) Mean±SD Median (Min-Max) Before Luting 132.54±100.53 115.20 (5.57-439.60) 157.85±113.50 135.50 (6.02-464.20) 0.301 a After Luting 89.63±70.07 65.17 (4.71-268.50) 198.77±138.67 171.50 (10.26-571.20) <0.001 a Difference -42.91±113.82 -24.83 (-416.00-130.20) 40.93±146.94 27.10 (-427.31-385.20) 0.003 a SD: Standard Deviation, Min:Minimum, Max:Maximum, a: Mann-Whitney U test Table 2. Analysis of variations in variables between two groups: a comparative assessment from baseline to first week. Discussion This study provides novel evidence indicating that IL-18 levels in GCF increased significantly where FSMs were luted with resin cement. In contrast, IL-18 levels significantly declined in the control group using conventional GIC after one week, likely due to the impact of oral hygiene education. These findings led to the rejection of the initial null hypothesis as IL-18 levels in GCF around abutment teeth luted with RC were markedly elevated, exhibiting a progressive increase over time when compared to the levels observed with conventional GIC. The distinct IL-18 responses observed between RC and GIC may be attributed to the clinical performance and biological behavior of these luting materials. Because the long-term stability of FSMs largely depends on the properties of the cement used, evaluating the potential effects of these materials on periodontal tissues is clinically relevant. The structural design of FSMs inherently exposes luting agents to constant salivary contact, consequent to their configuration. Over time, space maintainers can become dislodged, particularly when conventional GIC materials are used. This phenomenon can primarily be attributed to the gradual dissolution and degradation of the bonding material 23 , 24 . Resin cement was developed to address these limitations, offering superior mechanical properties and higher bond strength 25 . With advantages such as increased compressive and flexural strength, low thermal expansion, and reduced marginal permeability, RC provides improved retention and durability compared with traditional materials 26 , 27 . However, the challenge of removing excess cement from difficult to access subgingival margins remains a significant barrier to the successful application of resin cement for bonding restorations 25 . Given these material characteristics, this study evaluated both RC and GIC to assess their respective impacts on gingival health and inflammatory response in pediatric patients. Before the application of FSM luting, all participants in this study received verbal instruction on oral hygiene practices 28 . The analysis revealed no statistically significant differences in the GI, PI, and PPD measurements among the various cement types utilized for luting across all subjects at the one-week follow-up evaluation. Although statistically significant results were not achieved, a noticeable decline in both GI and PI values was observed. The improvement in oral hygiene is likely due to the educational interventions but may also be influenced by the follow-up appointment scheduled for a week later. Patients may enhance their oral care behaviors, anticipating evaluation of their progress, which reflects the Hawthorne effect, where behavior changes in response to being observed 24 . Consistent with previous research, this study also recorded an increase in PPD values over a brief duration of one week, although the change was not statistically significant 29 . In a study assessing the effectiveness of written versus verbal oral hygiene training for FSMs, Arikan et al. 28 observed that over a follow-up period of 3, 6, and 9 months, there was a statistically significant deterioration in GI, PI, and PPD values. This indicated a progressive worsening of periodontal health metrics as time elapsed. Conversely, a review of comparable research reported a notable enhancement in GI and PI metrics among pediatric patients utilizing FSMs during their 6-month follow-up evaluation 30 . Hosseinipour et al. conducted a study examining the effects of FSMs in children aged 6–12 over a 6-month follow-up period 29 . Their findings demonstrated a significant increase in GI and PPD values, specifically in the distolingual and mesiolingual areas associated with space maintainer bands. In contrast to the previous studies, the present study involved a follow-up period of just one week for the patients. It is essential to account for the discrepancies between our findings and those of other research when interpreting the results. To maintain the standardization of the study protocol, a one-week follow-up assessing GI, PI, and PPD was intentionally scheduled to elucidate the changes in IL-18 levels without the confounding influence of the patient's oral hygiene. IL-18 functions as a proinflammatory cytokine that augments the immune response through the coordination of other proinflammatory mediators such as IL-1β and TNF-α 31 . Studies, including those by Orozco et al. have shown that IL-18 is the predominant cytokine in gingival and periodontal disease sites, with inflammation markedly increasing local cytokine production in GCF 16 . Furthermore, previous findings revealed that pro-inflammatory cytokines such as IL-18, IL-17, and TNF-α are upregulated in periodontal disease. Elevated concentrations of these mediators have been consistently observed in various biological samples, including GCF, saliva, serum, and gingival tissue biopsies 32 – 34 . In the present study, IL-18 levels in the RC group increased significantly within one week, indicating an inflammatory response. However, it is insufficient to evaluate IL-18 levels in isolation when drawing definitive conclusions regarding periodontal inflammation. IL-18 is only one of several proinflammatory cytokines implicated in the pathogenesis of periodontal diseases. The expression of IL-18 and its contribution to pathogenesis are modulated by various cytokines. A more comprehensive understanding of IL-18's functions can be achieved by evaluating these cytokines in conjunction. In this study, gingival inflammation is hypothesized to arise from the persistence of cement remnants within the gingival crevicular sulcus, as well as from unpolymerized residual monomers present in the resin composite cement or the inherent chemical characteristics of the resin cement itself. Our analysis of the luting cement revealed its composition includes urethane dimethacrylate (UDMA), triethylene glycol dimethacrylate (TEGDMA), multifunctional monomers, photoinitiators, fumed silica, and an adhesive accelerator; however, the specific ratios of these components were not disclosed 35 . Research has demonstrated that the constituents of resins can leach into the oral environment, potentially leading to various adverse effects, which are influenced by their chemical composition, pH, and polymerization characteristics 36 . In the RC used in this study, UDMA was utilized as a substitute for HEMA. A cytotoxicity assessment by Diomede et al. revealed that UDMA reduced the viability of gingival fibroblasts by 50% after a 24-hour incubation period and significantly modulated cytokines including IL-6, IL-8, IL-12, and TNF-α 37 . Another study noted that the amount of UDMA released from composite resins was low compared to toxic doses but still had a cytotoxic effect on human gingival fibroblast cells, without increasing IL-1β expression 38 . Cytotoxicity studies on TEGDMA and UDMA have shown that these monomers significantly reduce cell viability and induce genotoxic effects leading to DNA damage 39 , 40 . These biologic responses align with the elevated IL-18 levels observed in the RC group, supporting the conclusion that RC may induce periodontal inflammation. Despite the promising findings of the present study, several limitations should be acknowledged. Although a split-mouth design was employed to minimize inter-individual variability, the allocation of luting materials was not randomized. The fixed assignment of resin cement to the left side and glass ionomer cement to the right side may have introduced potential side-related bias, including differences in chewing preference, oral hygiene habits, or anatomical variations. Therefore, the findings should be interpreted with caution. Another limitation of the study was that the evaluation of IL-18 levels was evaluated only at the 7-day time point, which may not fully reflect the dynamic inflammatory response following cementation. Although IL-18 was selected as a biomarker to evaluate inflammatory status, assessing only this cytokine and at only one interval provides a restricted view of the complex network of proinflammatory mediators involved in periodontal inflammation. This limitation was further compounded by challenges inherent to working with a pediatric population. Due to the lower volume of GCF in children compared to adults, sample collection required extended time and, even then, some samples remained below detectable thresholds during ELISA analysis. These undetectable samples led to the exclusion of certain participants, thereby reducing the effective sample size and impacting the comprehensiveness of the inflammatory assessment. Conclusion Considering the limitations of this study, our comparison between GIC and RC revealed that oral hygiene training conducted before luting and during the one-week follow-up contributed to decreases in periodontal metrics across all patients, although these improvements did not reach statistical significance. A significant decrease in IL-18 levels was observed in the GIC group after one week, whereas the RC group showed a significant increase, suggesting a more pronounced inflammatory response associated with RC usage. However, the underlying chemical components responsible for this response remain unclear. Future studies should identify the specific RC constituents and investigate their biological effects through targeted cellular research. Declarations Acknowledgements All authors thank Assoc. Dr. Batuhan Bakırarar (PhD) for providing statistical assistance in the preparation of the manuscript. Author contributions statement S.S.A.D. and O.D. designed the study. A.V. and E.N.A. performed the formal analysis. S.S.A.D., O.D., A.V analyzed the data. O.D. and E.N.A. wrote the manuscript. S.S.A.D. and O.D. contributed to review, and editing. All authors contributed to editorial changes in the manuscript. All authors reviewed the manuscript. Funding The author received no funding f or this work. Availability of data The datasets analyzed during this study are available upon request. Competing interests The authors declare no competing interests. Ethics approval and consent to participate This study was approved by the Ethics Committee of Afyonkarahisar Health Sciences University, Faculty of Medicine (reference number: 2022/7/336). All procedures within this study were performed in accordance with the relevant guidelines and regulations of the Declaration of Helsinki. Informed consent was obtained from all subjects and/or their legal guardian(s). All methods were carried out in accordance with relevant guidelines and regulations. References Law CS. Management of premature primary tooth loss in the child patient. J. Calif. Dent. Assoc . 41 (8), 612–618. (2013). Nascimento EB, Rodrigues R & Manso MC. Prevalence of dental floss use in deciduous dentition: A systematic review and meta‐analysis. Int. J. Dent. Hyg. 21 (1), 116–127 (2023). Watt E, Ahmad A, Adamji R, Katsimbali A, Ashley P & Noar J. Space maintainers in the primary and mixed dentition – a clinical guide. Br. Dent. J. 225 (4), 293–298 (2018). Dogan O & Dogan SSA. 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Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr. 83 (2), 447-455 (2006). Doğan SSA, Karakan NC & Doğan Ö. Effects of topically administered 0.6% hyaluronic acid on the healing of labial frenectomy in conventional and 940-nm indium gallium arsenide phosphide (InGaAsP) diode laser techniques in pediatric patients: a randomized, placebo-controlled clinical study. Lasers Med. Sci. 39 (1), 48 (2024). Silness J & Loe H. Periodontal Disease in Pregnancy. II. Correlation Between Oral Hygiene and Periodontal Condition. Acta Odontol. Scand. 22 (1), 121–135 (1964). Cebesoy EI, Altaca M, Kocak-Oztug NA, Bingül I & Cifcibasi E. Associations between interleukin-10, -12, and − 18 and periodontal health and disease: a cross-sectional study. Clin. Oral Investig. 28 (8), 458 (2024). Qudeimat MA & Sasa IS. Clinical success and longevity of band and loop compared to crown and loop space maintainers. Eur. Arch. Paediatr. Dent. 16 (5), 391–396 (2015). Cengiz A & Karayilmaz H. Comparative evaluation of the clinical success of 3D‐printed space maintainers and band–loop space maintainers. Int. J. Paediatr. Dent. 34 (5), 584–592 (2024). Heboyan A, et al. Dental luting cements: an updated comprehensive review. Molecules. 28 (4), 1619 (2023). Akehashi S, Takahashi R, Nikaido T, Burrow MF & Tagami J. Enhancement of dentin bond strength of resin cement using new resin coating materials. Dent. Mater. J. 38 (6), 955–962 (2019). Wiedenmann F, Becker F, Eichberger M & Stawarczyk B. Measuring the polymerization stress of self-adhesive resin composite cements by crack propagation. Clin. Oral Investig. 25 (3), 1011–1018 (2021). Arikan F, Eronat N, Candan U & Boyacioğlu H. Periodontal conditions associated with space maintainers following two different dental health education techniques. J. Clin. Pediatr. Dent. 31 (4), 229–234 (2007). Hosseinipour ZS, Poorzandpoush K, Heidari A & Ahmadi M. Assessment of Periodontal parameters following the use of fixed and removable space maintainers in 6-12-year olds. Int. J. Clin. Pediatr. Dent. 12 (5), 405–409 (2019). Arikan V, Kizilci E, Ozalp N & Ozcelik B. Effects of fixed and removable space maintainers on plaque accumulation, periodontal health, candidal and Enterococcus Faecalis carriage. Med. Princ. Pract. 24 (4), 311–317 (2015). da Silva MK, de Carvalho ACG, Alves EHP, da Silva FRP, Pessoa L dos S & Vasconcelos DFP. Genetic factors and the risk of periodontitis development: Findings from a systematic review composed of 13 studies of meta-analysis with 71,531 participants. Int. J. Dent. 2017 (1), 1–9 (2017). Papageorgiou SN, Reichert C, Jäger A & Deschner J. Effect of overweight/obesity on response to periodontal treatment: systematic review and a meta‐analysis. J. Clin. Periodontol. 42 (3), 247–261 (2015). Özçaka Ö, Nalbantsoy A & Buduneli N. Interleukin-17 and interleukin-18 levels in saliva and plasma of patients with chronic periodontitis. J. Periodontal Res. 46 (5), 592-598 (2011). Techatanawat S, et al. Salivary and serum interleukin-17A and interleukin-18 levels in patients with type 2 diabetes mellitus with and without periodontitis. PLoS One. 15 (2), e0228921 (2020). High-Q-Bond Band Details. Available at: https://www.bjmlabs.com/products/ orthodontic/high-q-bond-band-detail. (Accessed: 1 September 2025). Monteiro GQM, et al. In vitro biological response to a self-adhesive resin cement under different curing strategies. J. Biomed. Mater. Res. B Appl. Biomater. 92 (2), 317–321 (2010). Diomede F, et al. Pro-inflammatory cytokine release and cell growth inhibition in primary human oral cells after exposure to endodontic sealer. Int. End. J. 47 (9), 864–872 (2014). Moharamzadeh K, Van Noort R, Brook IM & Scutt AM. Cytotoxicity of resin monomers on human gingival fibroblasts and HaCaT keratinocytes. Dent. Mater. J. 23 (1), 40–44 (2007). Kurt A, et al. Evaluation of residual monomer release and toxicity of self-adhesive resin cements. Dent. Mater. J. 37 (1), 40–48 (2018). Durner J, Wellner P, Hickel R & Reichl FX. Synergistic interaction caused to human gingival fibroblasts from dental monomers. Dent. Mater. J. 28 (8), 818–823 (2012). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8793963","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":614590256,"identity":"080fd62f-23d5-417e-af8b-396286c30f4c","order_by":0,"name":"Suat Serhan Altıntepe Dogan","email":"","orcid":"","institution":"Afyonkarahisar Sağlık Bilimleri Üniversitesi","correspondingAuthor":false,"prefix":"","firstName":"Suat","middleName":"Serhan Altıntepe","lastName":"Dogan","suffix":""},{"id":614590257,"identity":"39603f5c-9cac-47ef-9a2d-a862029c3d93","order_by":1,"name":"Ozgur Dogan","email":"","orcid":"","institution":"Afyonkarahisar Sağlık Bilimleri Üniversitesi","correspondingAuthor":false,"prefix":"","firstName":"Ozgur","middleName":"","lastName":"Dogan","suffix":""},{"id":614590258,"identity":"f79e5810-b1d4-4f45-a457-b9db15fd6ceb","order_by":2,"name":"Esra Nur Akgul","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYJACxgYGBhk29uaDDz4AeWzsRGrh4eM5lmw4A6SFmVgtchI5ZsI8IC4hLeYSuQ8/zvh1mIcNqIXZ5tc2eT5mBsYPH3Nwa7GckW4subEPqIXnWdnj3L7bhm3MDMySM7fh1mJwI41B8mEPUAt78nbj3J7bjEAtbMy8+LUw/wRrYUgwk7bsuW1PjBY2yQ0/gFo4UsykGX7cTiSs5cwzNsuZDelAvwADubfhdnIbM2Mzfr8cT2O+2fPHWk6+HRiVP/7ctp0PZHz4iEcLGDC2oTBA8UQQ/MFgjIJRMApGwShAAADYRlFocM+5lAAAAABJRU5ErkJggg==","orcid":"","institution":"Ankara Medipol University","correspondingAuthor":true,"prefix":"","firstName":"Esra","middleName":"Nur","lastName":"Akgul","suffix":""},{"id":614590259,"identity":"5e2aa81a-7a59-46d9-b4b9-04d4558707df","order_by":3,"name":"Ayhan Vurmaz","email":"","orcid":"","institution":"Afyonkarahisar Sağlık Bilimleri Üniversitesi","correspondingAuthor":false,"prefix":"","firstName":"Ayhan","middleName":"","lastName":"Vurmaz","suffix":""}],"badges":[],"createdAt":"2026-02-05 08:09:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8793963/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8793963/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105909046,"identity":"601ab58f-e00b-43ed-8dba-0f0e2ff0853e","added_by":"auto","created_at":"2026-04-01 10:41:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":231004,"visible":true,"origin":"","legend":"\u003cp\u003eThe study flow chart follows CONSORT guidelines for clinical trials.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8793963/v1/05598a5e14451e5d27d073ca.png"},{"id":105908932,"identity":"b76c57ef-44d6-4650-b4fd-2a52823ab208","added_by":"auto","created_at":"2026-04-01 10:40:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":512159,"visible":true,"origin":"","legend":"\u003cp\u003eAn illustration of the patient included in the study.\u003cstrong\u003e \u003c/strong\u003e(A) Baseline intraoral photograph presented prior to the procedure. (B) The GCF sample immediately before the luting process. (C) Acquisition of the GCF sample during the one-week follow-up session post-luting. (D) In certain instances, GCF samples were obtained from a site approved by the FSM due to insufficient GCF volume being collected initially.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8793963/v1/df6a2ba61fbe19944fca1bc6.png"},{"id":105908958,"identity":"d3e3cfb8-bb86-42c7-a145-35211a544597","added_by":"auto","created_at":"2026-04-01 10:40:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":44562,"visible":true,"origin":"","legend":"\u003cp\u003eTime-dependent variations in IL-18 levels among GIC and RC groups.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8793963/v1/1b5a5957885dbcf622f8061d.png"},{"id":105911062,"identity":"d0a0b270-f5dc-44c4-b9f4-25e19ee789c6","added_by":"auto","created_at":"2026-04-01 10:51:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1765451,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8793963/v1/d6125a34-8d7f-4168-b391-41ff47e18b52.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Effects of Fixed Space Maintainers Luted with Resin Cement on Interleukin-18 Levels in Gingival Crevicular Fluid","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFixed space maintainers (FSMs) are important preventive orthodontic devices used in pediatric dentistry. These devices are specifically designed to preserve the spaces left by premature tooth loss or planned tooth extractions. Maintaining these spaces is crucial for guiding the proper eruption of permanent teeth, contributing to a child\u0026rsquo;s healthy dental development\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Pediatric dentists are the most frequently consulted professionals during this stage, and their preventive practices significantly impact the preservation of the edentulous space during the transition from mixed dentition to permanent dentition\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFSMs need to remain cemented in the mouth for an extended period, as even a matter of days can be significant in this process. To achieve optimal results, the cementation process must be conducted with durable luting cement. Traditionally, it has been advised to cement FSMs using conventional glass ionomer cement (GIC)\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. However, over the past decade, resin cement (RC) has become increasingly prevalent\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e due to significant advancements in bonding technology and the rising adoption of adhesive resin cement within dentistry\u003csup\u003e\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. While RC has been adopted to potentially improve the longevity of FSMs, concerns arise regarding the possibility of residual luting cement extending into the gingival sulcus. Such remnants may contribute to periodontal inflammation, yet research examining this issue in pediatric patients remains limited.\u003c/p\u003e \u003cp\u003eTo better understand the biological implications of cement remnants, gingival crevicular fluid (GCF) serves as the primary medium for analyzing alterations in the local tissue environment, thereby facilitating the assessment of periodontal health and disease. This fluid is instrumental in understanding the physiological changes occurring in periodontal conditions. The noninvasive collection of biomarkers in GCF is an essential diagnostic method for accurately assessing gingival health in clinical practice\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Numerous inflammatory cytokine biomarkers indicate the presence of gingival inflammation. Pro-inflammatory cytokines, tumor necrosis factor (TNF-α), anti-inflammatory cytokines, and matrix metalloproteinases play significant roles in regulating inflammatory responses\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAmong these biomarkers, interleukin-18 (IL-18) is a significant pro-inflammatory cytokine belonging to the interleukin-1 (IL-1) family. It is essential in the immune response to infections and various diseases\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. The function of IL-18 in the inflammatory response is to facilitate the expression of adhesion molecules on endothelial cells, thereby increasing the recruitment of immune cells to the site of inflammation. The accumulation of IL-18 in regions that are persistently exposed to irritants triggers chronic tissue damage, facilitating the progression of the disease's pathogenesis\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. The role of IL-18 in immune regulation and inflammation suggests that it may serve as a potential biomarker for tracking the progression of various diseases\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Studies have indicated that the expression levels of IL-18 are significantly elevated in gingival crevicular fluid and gingival tissue samples associated with gingival inflammation and periodontal diseases\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGiven these considerations, it is important to re-evaluate FSM cementation protocols, particularly when RC is used in areas close to the gingival pocket. However, current literature remains unclear about inflammation effects in the periodontal sulcus caused by using resin cement for luting space maintainers. The null hypothesis of this study states that FSMs luted with conventional GIC and those luted with resin cement result in similar alterations in IL-18 levels within the GCF of pediatric patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was designed as a non-randomized split-mouth clinical trial that was conducted at Afyonkarahisar Health Sciences University, Faculty of Dentistry, Department of Pediatric Dentistry clinic between June 2022 and June 2023. This study protocol was initiated following approval from the Ethics Committee of the Faculty of Medicine, Afyonkarahisar Health Sciences University (reference number: 2022/7/336), and all procedures were carried out in accordance with the ethical standards outlined in the Declaration of Helsinki. The protocol was retrospectively registered at ClinicalTrials.gov (Identifier: NCT06811597; registration date: 06 February 2025).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eComprehensive information was provided to all participants and parents regarding the importance of oral hygiene maintenance. Measures were taken to ensure that optimal oral hygiene standards were upheld throughout the study. This study was conducted under the Consolidated Standards of Reporting Trials (CONSORT) guidelines (Fig. 1) and ethical principles for medical research involving human subjects as outlined in the Declaration of Helsinki. All patients provided informed consent by signing a consent form.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample Size\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the scarcity of identical studies in the existing literature, the sample size calculation was based on an established effect size. The effect size was determined to be 0.55 for the difference in IL levels measured on the first and seventh days following the application of FSM bonding material to either the right or left side of the jaw. Using a paired t-test with a statistical power of 0.80, the minimum required sample size was calculated to be twenty-eight participants. To account for a potential 10% dropout rate, thirty-six participants were initially enrolled. The study ultimately concluded with thirty-one participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eInclusion Criteria\u003c/strong\u003e\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eChildren who do not have any underlying systemic diseases.\u003c/li\u003e\n \u003cli\u003eChildren have not received any antibiotic treatment in the past four months.\u003c/li\u003e\n \u003cli\u003eBoth girls and boys between the ages of 6 and 10.\u003c/li\u003e\n \u003cli\u003eThe second primary molar teeth (75 and 85) were extracted from patients due to caries and associated periapical pathologies.\u003c/li\u003e\n \u003cli\u003eExistence of the antagonistic tooth of the abutment tooth.\u003c/li\u003e\n \u003cli\u003eChildren and their parents willing to participate in the study and attend one week follow-up were included.\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eExclusion Criteria\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eChildren present with periodontal disease.\u003c/li\u003e\n \u003cli\u003eChildren with cognitive disabilities.\u003c/li\u003e\n \u003cli\u003eChildren with skeletal or dental malocclusion.\u003c/li\u003e\n \u003cli\u003eChildren and their parents who did not meet the specified criteria were excluded from the study.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Procedures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients who elected to undergo FSM treatment had previously visited the pediatric dentistry clinic at which their teeth, numbered 75 and 85, were extracted due to carious lesions and periapical pathologies. The extractions were performed at one-week intervals. This procedure was conducted utilizing behavioral guidance techniques while the patient was seated in the dental chair at the clinic. Following each tooth extraction, a week was designated for the healing of the extraction site. Subsequently, an appointment was scheduled for the following week to obtain impressions for the space maintainer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study examined various factors, including the patient\u0026rsquo;s age, gender, Plaque index (PI), Gingival Index (GI), and Periodontal Probing Depth (PPD). All measurements were conducted utilizing a Williams periodontal probe (122-006, HuFriedy, Chicago, IL, USA) on the multiple surfaces of each tooth: mesiobuccal, buccal, distobuccal, distolingual, lingual, and mesiolingual\u003csup\u003e20\u003c/sup\u003e. The GI scores\u003csup\u003e21\u003c/sup\u003e, which range from 0 to 3, were determined by aggregating the scores from the buccal, lingual, mesial, and distal surfaces of each tooth. This total was then divided by four to yield an average score, where a value of 0 signifies healthy gingival conditions and a score of 3 denotes severe inflammation of the gums characterized by spontaneous bleeding. The PI scores [21] for each tooth were computed on a scale of 0 to 3, derived from the scores assigned to the buccal, lingual, mesial, and distal surfaces. A score of 0 indicates the absence of visible plaque, while a score of 3 denotes severe plaque accumulation. The cumulative score for each tooth was then averaged by dividing the total by four.\u003c/p\u003e\n\u003cp\u003eOrthodontic bands (Morelli, Alameda Jundia\u0026iacute;, 230/250, Sorocaba 18085-090, Sao Paulo, Brazil) corresponding to the identified tooth numbers were promptly selected and fitted on the same day. The loop component was shaped and contoured to align with the dental arch and then soldered into place. The bands were polished using a periodontal polishing rubber without polishing paste. Before luting the FSMs, GCF samples were collected from the mid-buccal area of the targeted teeth using Periopaper (Periopaper\u0026reg;, Proflow Inc. Amityville, NY, USA). The strips were carefully placed into the gingival sulcus or periodontal pocket until slight resistance was felt and retained for 1 minute\u003csup\u003e22\u003c/sup\u003e. Contaminated or unsuitable periopapers were discarded, and a new sample was obtained if necessary. All collected Periopaper strips were pooled in Eppendorf tubes (Eppendorf\u0026reg;, Eppendorf AG, Hamburg, Germany) containing 40 \u0026mu;L of 1% Bovine Serum Albumin solution in phosphate-buffered saline (pH:7.4) with Tween, centrifuged at 12,000 g for 5 minutes at 4 \u0026ordm;C and stored at \u0026minus;80 \u0026deg;C in an Ultra Low-Temperature Freezer (Qingdao Carebios Biological Technology Co. Shandong., China) until they were required for laboratory analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA split-mouth design was used to minimize inter-individual variability. However,\u0026nbsp;allocation was not randomized. The luting materials were predetermined as follows: Resin cement (RC) was applied to the left mandibular first permanent molar (tooth 36). Glass ionomer cement (GIC) was applied to the right mandibular first permanent molar (tooth 46). This fixed allocation was implemented to standardize clinical procedures across participants. All clinical procedures were performed by the same pediatric dentist to minimize operator variability.\u003c/p\u003e\n\u003cp\u003eAfter the procedure, patients were instructed to refrain from all oral intake for the initial 30 minutes post-procedure and to avoid chewing hard foods for a subsequent 24-hour period. The patients were once more advised regarding the importance of oral hygiene education. After the initial evaluation, periodontal parameters were reassessed in the patients scheduled for follow-up one week later. Additionally, a GCF sample was recollected from the same site for analysis. ELISA assays were conducted to quantify IL-18 levels in GCF samples. After the implementation of these protocols, patients were advised to schedule their regular follow-up examinations (Fig. 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;2.\u0026nbsp;\u003c/strong\u003eAn illustration of the patient included in the study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(A) Baseline intraoral photograph presented prior to the procedure. (B) The GCF sample immediately before the luting process. (C) Acquisition of the GCF sample during the one-week follow-up session post-luting. (D) In certain instances, GCF samples were obtained from a site approved by the FSM due to insufficient GCF volume being collected initially.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIL-18 Measurement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe assays were conducted employing human-specific IL-18 ELISA kits sourced (Elabscience Biotechnology, Houston, TX, 77079, USA). The procedures were carried out following the manufacturer\u0026apos;s specifications and protocols. Eppendorf tubes containing periopapers were equilibrated to room temperature for 20 minutes after the thawing process. The samples were then incubated on a rocking platform overnight at 4 \u0026deg;C. The concentrations of IL-18 in the GCF samples were quantitatively assessed using a commercially available enzyme-linked immunosorbent assay (ELISA) format on a Chemwell 2910 Microplate Spectrophotometer (Awareness Technology Inc., Palm City, USA). The assays were performed in 96-well plates (ISOLAB, Laborgerate GmbH, Istanbul, T\u0026uuml;rkiye). Standardized concentration curves and corresponding absorbance values were employed to quantify the IL-18 levels in patient samples, expressed in picograms per milliliter (pg/mL).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData analysis was conducted using SPSS version 24.0 (Statistical Package for the Social Sciences, IBM, NY, USA). Descriptive statistics for quantitative variables were reported as mean \u0026plusmn; standard deviation and median (range: minimum-maximum). Both mean \u0026plusmn; standard deviation and median (minimum-maximum) were utilized to describe quantitative variables. The Mann-Whitney U test was employed to assess differences between two categories of qualitative variables for the quantitative variable, given the violation of normal distribution assumptions. The Wilcoxon Signed Ranks test was used to evaluate differences between two dependent quantitative variables due to normality violations. The results were evaluated at the p \u0026lt;0.05 significance level.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eUpon analyzing the changes in PI measurements before and after the luting of space maintainers, only the variations observed in teeth 36 and 46 were statistically significant (p=0.002). The PI values recorded from the teeth designated for the luting of the fixed space maintainers showed a statistically significant increase in comparison to the PI values obtained during the control sessions within the first week (Table 1).\u003c/p\u003e\n\u003cp\u003eIn the scope of statistical analysis, we evaluated pre- and post-intervention differences and investigated whether there were statistically significant distinctions between the right and left sides regarding these differences. Our results demonstrated no significant difference across all evaluated parameters between the right and left sides (p\u0026gt;0.05) (Table 1).\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"617\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTooth\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAvg.\u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (Min-Max)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\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=\"12\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.46\u0026plusmn;0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.33 (0.00-1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.104\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.30\u0026plusmn;0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.33 (0.00-1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.40\u0026plusmn;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.33 (0.00-1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.741\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.39\u0026plusmn;0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.33 (0.00-1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e-0.16\u0026plusmn;0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-1.33-0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.311\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e-0.01\u0026plusmn;0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-1.17-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.20\u0026plusmn;0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (0.00-1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.909\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.20\u0026plusmn;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (0.00-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.30\u0026plusmn;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.33 (0.00-1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.842\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.28\u0026plusmn;0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.16 (0.00-1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.00\u0026plusmn;0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-1.16-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.964\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e-0.02\u0026plusmn;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-1.17-1.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"12\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.71\u0026plusmn;0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.66 (0.00-2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.002\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.40\u0026plusmn;0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.33 (0.00-1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.63\u0026plusmn;0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.66 (0.00-2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.144\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.47\u0026plusmn;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.33 (0.00-2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e-0.31\u0026plusmn;0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e-0.16 (-1.84-0.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.485\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e-0.16\u0026plusmn;0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e-0.17 (-1.67-1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.45\u0026plusmn;0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.33 (0.00-1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.126\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.58\u0026plusmn;0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.66 (0.00-2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.64\u0026plusmn;0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.66 (0.00-1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.370\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.58\u0026plusmn;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.50 (0.00-2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.13\u0026plusmn;0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-1.00-1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.228\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e-0.06\u0026plusmn;0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-1.00-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"12\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePPD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.28\u0026plusmn;0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1.16 (1.00-2.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.497\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.33\u0026plusmn;0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1.16 (1.00-2.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.33\u0026plusmn;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1.16 (1.00-2.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.192\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.44\u0026plusmn;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1.33 (1.00-2.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.05\u0026plusmn;0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-0.50-0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.352\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.11\u0026plusmn;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-0.50-1.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.08\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1.00 (1.00-1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.686\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.09\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1.00 (1.00-1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eBefore Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.06\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1.00 (1.00-1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.137\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eAfter Luting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.10\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1.00 (1.00-1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eRight (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.01\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-0.50-0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003e0.440\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eLeft (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 149px;\"\u003e\n \u003cp\u003eDifference for Tooth 74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.04\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e0.00 (-0.50-0.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eGI: Gingival Index, PI: Plaque Index, PPD: Periodontal Probing Depth, AVG:Average, SD:Standard Deviation, Min:Minimum, Max:Maximum, \u0026nbsp;a: Wilcoxon Signed Rank test, b: Mann-Whitney U test\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;1.\u0026nbsp;\u003c/strong\u003eVariations in periodontal indices were observed over the duration of the one-week study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntragroup Comparisons\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUpon conducting an analysis of the variations in IL-18 levels, a statistically significant difference in IL-18 production was observed when utilizing conventional GIC for luting in the right teeth (p=0.046). In the RC group, the IL-18 measurements recorded at two distinct time intervals for luting the teeth on the left side showed a significant difference (p=0.036). When IL-18 averages from the pre-luting phase and the first-week control session were compared, a statistically significant increase in IL-18 levels was observed. The changes in IL-18 levels over time are illustrated in Fig. 3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntergroup Comparisons\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 presents a comparative analysis of IL-18 levels between the two groups, highlighting the measurements taken before, after, and the changes between these time points for each group. Significant differences were detected in the measurements taken after luting and the comparisons conducted before/after differences (p\u0026lt;0.001 and p=0.003, respectively). Before the luting, the average IL-18 levels in the GIC group were recorded at 132.54 \u0026plusmn; 100.53 pg/mL, whereas in the RC group, the average was higher at 157.85 \u0026plusmn; 113.50 pg/mL. At the after-luting time point, the mean IL-18 concentration was observed to be 89.63 \u0026plusmn; 70.07 pg/mL in the GIC group, whereas, in the RC group, the mean IL-18 level was significantly higher at 198.77 \u0026plusmn; 138.67 pg/mL. A decrease was observed in the GIC group between the before/after times, and an increase was observed in the RC group.\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"671\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGIC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\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 style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Min-Max)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Min-Max)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore Luting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e132.54\u0026plusmn;100.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e115.20\u003c/p\u003e\n \u003cp\u003e(5.57-439.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e157.85\u0026plusmn;113.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e135.50\u003c/p\u003e\n \u003cp\u003e(6.02-464.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.301\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter Luting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e89.63\u0026plusmn;70.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e65.17\u003c/p\u003e\n \u003cp\u003e(4.71-268.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e198.77\u0026plusmn;138.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e171.50\u003c/p\u003e\n \u003cp\u003e(10.26-571.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e-42.91\u0026plusmn;113.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e-24.83\u003c/p\u003e\n \u003cp\u003e(-416.00-130.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e40.93\u0026plusmn;146.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e27.10\u003c/p\u003e\n \u003cp\u003e(-427.31-385.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eSD: Standard Deviation, Min:Minimum, Max:Maximum, a: Mann-Whitney U test\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;2.\u0026nbsp;\u003c/strong\u003eAnalysis of variations in variables between two groups: a comparative assessment from baseline to first week.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides novel evidence indicating that IL-18 levels in GCF increased significantly where FSMs were luted with resin cement. In contrast, IL-18 levels significantly declined in the control group using conventional GIC after one week, likely due to the impact of oral hygiene education. These findings led to the rejection of the initial null hypothesis as IL-18 levels in GCF around abutment teeth luted with RC were markedly elevated, exhibiting a progressive increase over time when compared to the levels observed with conventional GIC.\u003c/p\u003e \u003cp\u003eThe distinct IL-18 responses observed between RC and GIC may be attributed to the clinical performance and biological behavior of these luting materials. Because the long-term stability of FSMs largely depends on the properties of the cement used, evaluating the potential effects of these materials on periodontal tissues is clinically relevant. The structural design of FSMs inherently exposes luting agents to constant salivary contact, consequent to their configuration. Over time, space maintainers can become dislodged, particularly when conventional GIC materials are used. This phenomenon can primarily be attributed to the gradual dissolution and degradation of the bonding material\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eResin cement was developed to address these limitations, offering superior mechanical properties and higher bond strength\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. With advantages such as increased compressive and flexural strength, low thermal expansion, and reduced marginal permeability, RC provides improved retention and durability compared with traditional materials\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. However, the challenge of removing excess cement from difficult to access subgingival margins remains a significant barrier to the successful application of resin cement for bonding restorations\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Given these material characteristics, this study evaluated both RC and GIC to assess their respective impacts on gingival health and inflammatory response in pediatric patients.\u003c/p\u003e \u003cp\u003eBefore the application of FSM luting, all participants in this study received verbal instruction on oral hygiene practices\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. The analysis revealed no statistically significant differences in the GI, PI, and PPD measurements among the various cement types utilized for luting across all subjects at the one-week follow-up evaluation. Although statistically significant results were not achieved, a noticeable decline in both GI and PI values was observed. The improvement in oral hygiene is likely due to the educational interventions but may also be influenced by the follow-up appointment scheduled for a week later. Patients may enhance their oral care behaviors, anticipating evaluation of their progress, which reflects the Hawthorne effect, where behavior changes in response to being observed\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eConsistent with previous research, this study also recorded an increase in PPD values over a brief duration of one week, although the change was not statistically significant\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. In a study assessing the effectiveness of written versus verbal oral hygiene training for FSMs, Arikan et al. \u003csup\u003e28\u003c/sup\u003e observed that over a follow-up period of 3, 6, and 9 months, there was a statistically significant deterioration in GI, PI, and PPD values. This indicated a progressive worsening of periodontal health metrics as time elapsed. Conversely, a review of comparable research reported a notable enhancement in GI and PI metrics among pediatric patients utilizing FSMs during their 6-month follow-up evaluation\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHosseinipour et al. conducted a study examining the effects of FSMs in children aged 6\u0026ndash;12 over a 6-month follow-up period\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Their findings demonstrated a significant increase in GI and PPD values, specifically in the distolingual and mesiolingual areas associated with space maintainer bands. In contrast to the previous studies, the present study involved a follow-up period of just one week for the patients. It is essential to account for the discrepancies between our findings and those of other research when interpreting the results. To maintain the standardization of the study protocol, a one-week follow-up assessing GI, PI, and PPD was intentionally scheduled to elucidate the changes in IL-18 levels without the confounding influence of the patient's oral hygiene.\u003c/p\u003e \u003cp\u003eIL-18 functions as a proinflammatory cytokine that augments the immune response through the coordination of other proinflammatory mediators such as IL-1β and TNF-α\u003csup\u003e31\u003c/sup\u003e. Studies, including those by Orozco et al. have shown that IL-18 is the predominant cytokine in gingival and periodontal disease sites, with inflammation markedly increasing local cytokine production in GCF\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Furthermore, previous findings revealed that pro-inflammatory cytokines such as IL-18, IL-17, and TNF-α are upregulated in periodontal disease. Elevated concentrations of these mediators have been consistently observed in various biological samples, including GCF, saliva, serum, and gingival tissue biopsies\u003csup\u003e\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. In the present study, IL-18 levels in the RC group increased significantly within one week, indicating an inflammatory response. However, it is insufficient to evaluate IL-18 levels in isolation when drawing definitive conclusions regarding periodontal inflammation. IL-18 is only one of several proinflammatory cytokines implicated in the pathogenesis of periodontal diseases. The expression of IL-18 and its contribution to pathogenesis are modulated by various cytokines. A more comprehensive understanding of IL-18's functions can be achieved by evaluating these cytokines in conjunction.\u003c/p\u003e \u003cp\u003eIn this study, gingival inflammation is hypothesized to arise from the persistence of cement remnants within the gingival crevicular sulcus, as well as from unpolymerized residual monomers present in the resin composite cement or the inherent chemical characteristics of the resin cement itself. Our analysis of the luting cement revealed its composition includes urethane dimethacrylate (UDMA), triethylene glycol dimethacrylate (TEGDMA), multifunctional monomers, photoinitiators, fumed silica, and an adhesive accelerator; however, the specific ratios of these components were not disclosed\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eResearch has demonstrated that the constituents of resins can leach into the oral environment, potentially leading to various adverse effects, which are influenced by their chemical composition, pH, and polymerization characteristics\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. In the RC used in this study, UDMA was utilized as a substitute for HEMA. A cytotoxicity assessment by Diomede et al. revealed that UDMA reduced the viability of gingival fibroblasts by 50% after a 24-hour incubation period and significantly modulated cytokines including IL-6, IL-8, IL-12, and TNF-α\u003csup\u003e37\u003c/sup\u003e. Another study noted that the amount of UDMA released from composite resins was low compared to toxic doses but still had a cytotoxic effect on human gingival fibroblast cells, without increasing IL-1β expression\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. Cytotoxicity studies on TEGDMA and UDMA have shown that these monomers significantly reduce cell viability and induce genotoxic effects leading to DNA damage\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e. These biologic responses align with the elevated IL-18 levels observed in the RC group, supporting the conclusion that RC may induce periodontal inflammation.\u003c/p\u003e \u003cp\u003eDespite the promising findings of the present study, several limitations should be acknowledged. Although a split-mouth design was employed to minimize inter-individual variability, the allocation of luting materials was not randomized. The fixed assignment of resin cement to the left side and glass ionomer cement to the right side may have introduced potential side-related bias, including differences in chewing preference, oral hygiene habits, or anatomical variations. Therefore, the findings should be interpreted with caution.\u003c/p\u003e \u003cp\u003eAnother limitation of the study was that the evaluation of IL-18 levels was evaluated only at the 7-day time point, which may not fully reflect the dynamic inflammatory response following cementation. Although IL-18 was selected as a biomarker to evaluate inflammatory status, assessing only this cytokine and at only one interval provides a restricted view of the complex network of proinflammatory mediators involved in periodontal inflammation. This limitation was further compounded by challenges inherent to working with a pediatric population. Due to the lower volume of GCF in children compared to adults, sample collection required extended time and, even then, some samples remained below detectable thresholds during ELISA analysis. These undetectable samples led to the exclusion of certain participants, thereby reducing the effective sample size and impacting the comprehensiveness of the inflammatory assessment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e Considering the limitations of this study, our comparison between GIC and RC revealed that oral hygiene training conducted before luting and during the one-week follow-up contributed to decreases in periodontal metrics across all patients, although these improvements did not reach statistical significance. A significant decrease in IL-18 levels was observed in the GIC group after one week, whereas the RC group showed a significant increase, suggesting a more pronounced inflammatory response associated with RC usage. However, the underlying chemical components responsible for this response remain unclear. Future studies should identify the specific RC constituents and investigate their biological effects through targeted cellular research.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors thank Assoc. Dr. Batuhan Bakırarar (PhD) for providing statistical assistance in the preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003eAuthor\u0026nbsp;contributions statement\u003c/p\u003e\n\u003cp\u003eS.S.A.D. and O.D.\u0026nbsp;designed the study. A.V. and E.N.A.\u0026nbsp;performed the formal analysis. S.S.A.D., O.D., A.V\u0026nbsp;analyzed the data.\u0026nbsp;O.D. and E.N.A. wrote the manuscript.\u0026nbsp;S.S.A.D. and O.D. contributed to review, and editing. All authors contributed to editorial changes in the manuscript. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe author received \u003cstrong\u003eno funding f\u003c/strong\u003eor this work.\u003c/p\u003e\n\u003cp\u003eAvailability of data\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during this study are available upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Afyonkarahisar Health Sciences University, Faculty of Medicine (reference number: 2022/7/336). All procedures within this study were performed in accordance with the relevant guidelines and regulations of the Declaration of Helsinki. Informed consent was obtained from all subjects and/or their legal guardian(s). All methods were carried out in accordance with relevant guidelines and regulations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLaw CS. Management of premature primary tooth loss in the child patient. \u003cem\u003eJ. Calif. Dent. Assoc\u003c/em\u003e. \u003cstrong\u003e41\u003c/strong\u003e(8), 612\u0026ndash;618. (2013).\u003c/li\u003e\n \u003cli\u003eNascimento EB, Rodrigues R \u0026amp; Manso MC. Prevalence of dental floss use in deciduous dentition: A systematic review and meta‐analysis.\u0026nbsp;\u003cem\u003eInt. J. Dent. Hyg.\u003c/em\u003e\u003cstrong\u003e21\u003c/strong\u003e(1), 116\u0026ndash;127 (2023).\u003c/li\u003e\n \u003cli\u003eWatt E, Ahmad A, Adamji R, Katsimbali A, Ashley P \u0026amp; Noar J. Space maintainers in the primary and mixed dentition \u0026ndash; a clinical guide. \u003cem\u003eBr. Dent. 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Evaluation of residual monomer release and toxicity of self-adhesive resin cements. \u003cem\u003eDent. Mater. J.\u003c/em\u003e\u003cstrong\u003e37\u003c/strong\u003e(1), 40\u0026ndash;48 (2018).\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Durner J, Wellner P, Hickel R \u0026amp; Reichl FX. Synergistic interaction caused to human gingival fibroblasts from dental monomers. \u003cem\u003eDent. Mater. J.\u003c/em\u003e\u003cstrong\u003e28\u003c/strong\u003e(8), 818\u0026ndash;823 (2012).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Fixed Space Maintainer, IL-18, Glass Ionomer Cement, Resin Cement, Gingival Inflammation","lastPublishedDoi":"10.21203/rs.3.rs-8793963/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8793963/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe aim of this study was to compare periodontal parameters and IL-18 (Interleukin-18) levels in gingival crevicular fluid (GCF) following fixed space maintainers (FSMs) luted with resin cement (RC) versus glass ionomer cement (GIC) in children. This split-mouth study was conducted in 31 children aged 6 to 10 years who received FSMs after premature loss of mandibular second primary molars. Left mandibular first molars were luted with self-adhesive RC and right molars with conventional GIC. Gingival Index (GI), Plaque Index (PI), and Periodontal Probing Depth (PPD) were recorded at baseline and 1 week follow-up. GCF was collected from the teeth using Periopaper® strips before luting and at the one-week follow-up and IL-18 levels were measured with ELISA. Mann-Whitney U test was used for intergroup comparisons, and Wilcoxon Signed Ranks test for intragroup comparisons. Pre- and post-luting differences were analyzed, revealing no significant distinctions between the right and left sides across the PI, GI, and PPD parameters (p \u0026gt; 0.05). In the RC group, IL-18 measurements taken at two different intervals showed a significant difference (p = 0.036). RC-luted FSMs showed increased IL-18, suggesting a heightened inflammatory response, possibly related to RC components.\u003c/p\u003e","manuscriptTitle":"The Effects of Fixed Space Maintainers Luted with Resin Cement on Interleukin-18 Levels in Gingival Crevicular Fluid","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 10:13:35","doi":"10.21203/rs.3.rs-8793963/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-28T08:54:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"84698914607584977915587067452363013514","date":"2026-04-24T08:26:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-07T10:36:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"161417597750771756578580606004499663989","date":"2026-03-30T10:09:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-30T07:50:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-30T07:47:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-18T05:38:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-13T12:46:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-13T12:42:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"858be11f-6d06-420e-85c6-2242c3b7c157","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":65397123,"name":"Health sciences/Diseases"},{"id":65397124,"name":"Health sciences/Health care"},{"id":65397125,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-04-01T10:13:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 10:13:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8793963","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8793963","identity":"rs-8793963","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}