Next Article in Journal
The Evaluation and Modification of Standard Airway Assessment Tests for Virtual Anaesthetic Assessments: A Pilot Study
Previous Article in Journal
Risk Stratification of QTc Prolongations in Hospitalized Cardiology and Gastroenterology Patients Using the Tisdale Score—A Retrospective Analysis
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JCM
Volume 14
Issue 2
10.3390/jcm14020340
jcm-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

The Effect of Peri-Implant Therapy on the Expression of Th17-Related Cytokines in Patients with Peri-Implant Mucositis and Peri-Implantitis: A Prospective Longitudinal Study

by
Líssya Tomaz da Costa Gonçalves
1,
Glaucia Schuindt Teixeira Neves
1,
Alexandre Marques Paes da Silva
1,
Daniel de Moraes Telles
1,
Carlos Marcelo da Silva Figueredo
2,3,*,
Eduardo José Veras Lourenço
1 and
Mayla Kezy Silva Teixeira
1
1
Department of Prosthodontics, School of Dentistry, Rio de Janeiro State University, Rio de Janeiro 20551-030, Brazil
2
School of Medicine and Dentistry, Griffith University, Queensland 4222, Australia
3
Division of Oral Diseases, Department of Dental Medicine, Karolinska Institute, 171 77 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(2), 340; https://doi.org/10.3390/jcm14020340
Submission received: 12 December 2024 / Revised: 1 January 2025 / Accepted: 4 January 2025 / Published: 8 January 2025
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
Browse Figures
Versions Notes

Abstract

Background/Objectives: Cytokines related to the Th17 response have been associated with peri-implant diseases; however, the effect of peri-implant therapy on their modulation remains underexplored. To evaluate the effect of peri-implant therapy on the expression of cytokines related to the Th17 response in the peri-implant crevicular fluid (PICF) (GM-CSF, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12 (p70), IL-17A, IL-21, IL-23, and TNF-α) of partially edentulous patients with peri-implant disease (PID). Methods: Thirty-seven systemically healthy individuals presenting with peri-implant mucositis (PIM) (n = 20) or peri-implantitis (PI) (n = 17) were treated and evaluated at baseline (T0) and three months after therapy (T1). Clinical parameters (probing depth (PD), clinical attachment level (CAL), plaque index, and bleeding on probing index (BoP), were evaluated. The PIM group underwent non-surgical therapy, while the PI group received a surgical approach. PICF was collected with absorbent paper strips and analyzed with a multiplex assay. Results: Eighty-eight implants were treated in 37 patients (56 in the PIM group and 32 in the PI group). After therapy, significant reductions in PD, CAL, plaque index, and BoP were observed in the PIM group (p < 0.05). In the PI group, significant reductions in PD, CAL, and BoP were noted (p < 0.05). The PIM group showed a significant reduction of IL-17A and TNF-α after therapy, while the PI group showed a significant reduction of IL-1β, IL-6, and TNF-α (p < 0.05). Conclusions: The peri-implant therapy for patients with PID reduced the expression of cytokines related to the Th17 response in PICF.

1. Introduction

Peri-implant mucositis (PIM) is an inflammatory condition characterized by inflammation of peri-implant tissues with bleeding and/or suppuration on probing, without accompanying bone loss. Peri-implantitis (PI) is distinguished by progressive bone loss, which may result in implant loss [1,2]. The prevalence of peri-implant diseases (PID) averages 47% for PIM and 20% for PI [3]. As the number of patients undergoing dental implant rehabilitation increases, biological complications also rise, presenting a relevant concern in dentistry [4,5,6,7].
The primary cause of inflammation development is the presence of biofilm in peri-implant tissues, which stimulates an immune host response [1]. The release of pro-inflammatory cytokines plays a crucial role in influencing the onset and progression of PID [7,8]. The precise significance of cytokines in PID remains still not clear, but it is recognized that a complex network of molecular interactions is associated with peri-implant inflammation and bone resorption in response to bacterial factors [9]. The inflammatory response leads to an increase in peri-implant crevicular fluid (PICF) production, enabling the identification of biomarkers through its analysis [10,11]. PICF collection is a simple, reproducible, and non-invasive technique that allows the assessment of specific sites of interest, acting as an important tool for monitoring disease activity [12,13,14].
T helper cells encompass seven subpopulations (Th1, Th2, Th9, Th17, Th22, Th, Tfh, Treg) and are pivotal in orchestrating the host immune response against bacterial aggression [15]. Th17 population is particularly significant in autoimmune and allergic diseases, as well as in host defense against pathogens [16,17]. In this context, understanding the activity of these cells is important to elucidate the immunoinflammatory mechanisms underlying peri-implant tissue destruction [18]. Previous cross-sectional studies have investigated the presence of cytokines from this group in PICF of patients with PIM and PI, establishing an association with disease activity [11,19]. However, the expression of these cytokines seems not to be different in PI and PIM, despite the presence of osteoclastogenesis [19]. As far as we know, prospective studies evaluating the expression of cytokines related to Th17 response and the effects of peri-implant therapy on modulating these biomarkers remain lacking.
Achieving success in peri-implant treatment poses a considerable challenge [20,21]. For patients with PIM, the approach usually involves non-surgical methods aimed at removing biofilm and calculus and providing oral hygiene instructions [22]. However, in cases of PI, non-surgical therapy seems ineffective in reducing probing depth (PD) and bleeding on probing [21,23,24]. As a result, surgical therapy becomes frequently necessary to improve access to the infected site and ensure satisfactory cleaning of the implant, which is crucial to obtaining favorable outcomes in PI treatment [25].
Therefore, this study aimed to evaluate the effect of peri-implant therapy on the expression of cytokines related to Th17 response (GM-CSF, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12 (p70), IL-17A, IL-21, IL-23, and TNF-α) in the peri-implant crevicular fluid of patients with peri-implant mucositis and peri-implantitis after a three-month follow-up.

2. Materials and Methods

2.1. Participants and Study Setting

This study was conducted at the School of Dentistry, State University of Rio de Janeiro, and obtained approval from the Research Ethics Committee under the number 69156722.5.0000.5259. All research participants were duly informed and signed a free and informed consent form, following the Declaration of Helsinki.
The individuals sampled for this present study were chosen based on the following inclusion criteria [26]:
  • Being systemically healthy or having controlled systemic conditions;
  • Being partially edentulous, with at least two osseointegrated implants affected by peri-implant disease (PID);
  • Having implant prosthetics that have been in function for a minimum of six months.
Exclusion criteria included individuals who [26]:
  • Had received periodontal or peri-implant treatment within six months before the study commencement;
  • Were pregnant or breastfeeding;
  • Were smokers;
  • Had taken antibiotics and anti-inflammatories within the last three months;
  • Had taken antiresorptive drugs within the last two years;
  • Had undergone radiotherapy, chemotherapy, or iodine therapy within the last two years.
The individuals were allocated in groups according to the following criteria:
Peri-implant mucositis group (PIM): clinical signs of inflammation, bleeding, and/or suppuration on probing; absence of radiographic bone loss beyond initial levels of bone remodeling [1,27].
Peri-implantitis group (PI): clinical signs of inflammation, bleeding, and/or suppuration on probing, accompanied by radiographic bone loss beyond initial levels of bone remodeling, compared to previous radiographs. In the absence of previous exams, criteria included probing depth ≥ 6 mm and radiographic bone loss ≥ 3 mm [1,27].

2.2. Clinical Examination

Each participant underwent both a clinical examination and a complete periapical full-mouth X-ray. The clinical examination was further divided into anamnesis and physical examination. During the anamnesis, demographic data and information regarding the time since their last periodontal and peri-implant maintenance therapy (PIMT) were gathered. The intraoral examination involved a complete periodontal chart, performed by a previously calibrated operator.
A standardized millimeter periodontal probe was used, and the measurements were rounded to the nearest millimeter (Hu-Friedy® PCP15, Chicago, IL, USA). Probing was performed at six sites per tooth/implant, assessing parameters such as PD (mm), clinical attachment level (CAL) (mm), bleeding on probing index (0 or 1), and visible plaque index (0 or 1) [28]. All clinical parameters and radiographs were evaluated before (baseline) and after three months of therapy (T1).

2.3. Peri-Implant Crevicular Fluid Collection

PICF collection was conducted under relative isolation, with cotton rolls around the implants, and surfaces were gently dried to prevent contamination from plaque or saliva. Two to three sites were selected per group, based on the deepest probing depth. Standardized absorbent paper strips (Periopaper®–Oraflow, Smithtown, NY, USA) were inserted 1–2 mm into the peri-implant sulcus, without traumatizing the tissues, remaining for up to 30 s [29]. Any samples contaminated with blood were discarded, while strips containing the fluid were stored in the same Eppendorf-type microtube, containing 200 μL of PBS buffer solution and 10 μL of protease inhibitor (Sigma-Aldrich, St. Louis, MO, USA). After 45 min, the paper strips were discarded, and the solution was centrifuged at 8000 rpm for five minutes in a laboratory centrifuge (NT800-Novatécnica, Piracicaba, SP, Brazil). Subsequently, the sample was transferred to a threaded microtube and frozen at −70 °C until analysis. FCPI collection was performed at baseline and T1.

2.4. Peri-Implant Therapy

The treatment of peri-implant diseases adhered to established protocols from prior consensus studies [30,31].
For the PIM group, a non-surgical approach was adopted, which included oral hygiene instruction, plaque control, and scaling of the implants using non-metallic manual curettes (Implacare-Hu-Friedy®, Chicago, IL, USA). Additionally, polishing procedures were conducted with a rubber cup, employing prophylactic paste (Maquira Shine-Maquira, Maringá, PR, Brazil) and bicarbonate jet (Jetlaxis Uno-Schuster, Santa Maria, RS, Brazil).
For the PI group, the same non-surgical approach was applied, followed by a surgical intervention performed by a single experienced periodontist after one month. If the prosthesis was screwed-retained, it was removed before surgery and subsequently reinstalled after the procedure. Surgery was performed using a total flap, with intrasulcular incisions made extending to one tooth or implant adjacent to each side. Granulation tissue was carefully removed with a Gracey curette (Hu-Friedy®, Chicago, IL, USA). The area was irrigated with sterile saline, and biofilm and calculus removal were performed using hand instruments. Polishing was performed with a bicarbonate jet (Jetlaxis Uno-Schuster, Santa Maria, RS, Brazil), a Robinson brush, and prophylactic paste (Maquira Shine-Maquira, Maringá, PR, Brazil). The region was then irrigated with 2% chlorhexidine solution (Chlorhexidine 2%-Maquira, Maringá, PR, Brazil), and the flap was repositioned and sutured. Postoperative medication (Amoxicillin 500 mg-8 in 8 h, for 7 days; Nimesulide 100 mg-12 in 12 h, for 3 days and Dipyrone-6 in 6 h, for 2 days) and mouthwash (chlorhexidine digluconate 0.12%-twice a day, for 14 days) were prescribed, with instructions not to brush the region until sutures were removed. The suture was removed 14 days after the surgical procedure.

2.5. Multiplex Assay

Cytokine levels (GM-CSF, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12 (p70), IL-17A, IL-21, IL-23, and TNF-α) were assessed through a multiplex microsphere immunoassay (Bioplex® 200-Bio-Rad, Hercules, CA, USA). Twenty-five microliters of each fluid sample were analyzed using a commercially available custom kit-Milliplex® Human High Sensitivity T Cell Magnetic Bead Panel Kit (Merck Millipore, Burlington, MA, USA), following the manufacturer’s instructions, using a 96-well plate.
Figure 1 provides a summary of the functions of the assessed cytokines in peri-implant diseases.

2.6. Statistical Analyses

Statistical analyses were conducted using SPSS, version 24 (IBM Corporation, Armonk, NY, USA). Data normality was assessed using the Kolmogorov-Smirnov test. Continuous variables were presented as mean and standard deviation, while categorical variables were presented as frequencies. The Mann-Whitney U test for independent samples was employed to compare continuous variables between groups, while the Chi-square test was utilized to compare frequencies between groups. Within-group analyses at different time points were conducted using the Wilcoxon test, adopting a significance level of p < 0.05. Pearson’s correlation coefficient was used to assess the correlation between cytokine levels, while Spearman’s correlation coefficient was used to assess the relationship between cytokine levels and clinical results. Significance levels for correlation were set at both p < 0.05 and p < 0.01.

3. Results

3.1. Demographic Data

The study included 37 participants who were either systemically healthy or had controlled systemic conditions. The demographic data are presented in Table 1.

3.2. Clinical Results

In the analyses of the PIM group, the treated implants showed a significant reduction of PD, CAL, and percentage of PId and BoP values (p = 0.001, p = < 0.001, p = 0.003, and p = < 0.001, respectively). The outcomes are presented in Table 2.
In the analyses of the PI group, the treated implants showed a reduction statistically significant of PD, CAL, and % BoP values (p = < 0.001, p = 0.004, and p = < 0.001, respectively). The outcomes are presented in Table 3.

3.3. Description of Implants

Eighty-eight implants were evaluated: 56 in the PIM group (63.63%) and 32 in the PI group (36.37%). The average functional time of the implants was 88.05 months (±59.53). It was evaluated categorically, divided into less than five years, between five and ten years, and more than ten years. No statistically significant differences were observed among these categories (p = 0.338).
The implants were evaluated according to their location in the arch, type of prosthetic platform, prosthetic connection (cemented or screwed), and whether they were splinted or non-splinted prostheses. The distribution of implants with PIM in the upper arch was significantly greater than those with PI (p = 0.002). In both groups, the prevalence of inflamed sites was significantly higher in the posterior region of the arches (p = < 0.001). Additionally, the prevalence of PIM was significantly higher in Morse Taper (MT) platform implants (p = < 0.001), while implants with PI had a significantly higher prevalence in the External Hexagon (EH) platform. Complete data are described in Table 4.

3.4. Immunological Results

In the analysis between the PIM and PI groups, no statistically significant differences were observed at baseline and T1 (p > 0.05). The cytokine levels were presented in total quantity (pg).
In the PIM group, a statistically significant reduction in the expression of IL-17A (p = 0.010) and TNF-α (p = 0.035) was observed after therapy.
In the PI group, there was a statistically significant reduction in the expression of IL-1β (p = 0.049), IL-6 (p = 0.01), and TNF-α (p = 0.011), with a trend towards a reduction in IFN-γ (p = 0.059).
The immunological data are described in Figure 2. IL-10 levels were below the detection limit and, therefore, were not included in the presentation.

3.5. Correlation Results

In the PIM group, after therapy, a significant negative correlation was observed between IFN-γ, IL-12, and IL-23 with PD. Additionally, IL-12 showed a significant negative correlation with the percentage of bleeding.
In the PI group, before therapy, there was a significant positive correlation between the levels of IFN-γ and IL-21 with PD. After therapy, IFN-γ showed a significant negative correlation with PD, while IL-21 showed a significant positive correlation with the percentage of plaque.
The correlations between cytokines and clinical data at both times (baseline and T1) in the PIM group are represented in Figure 3, whereas the correlations between cytokines and clinical data in the PI group are represented in Figure 4.
The correlations between cytokines in the PIM group in T0 and T1 are illustrated in Figure 5, while the correlations between cytokines in the PI group in T0 and T1 are demonstrated in Figure 6.

4. Discussion

In the present study, peri-implant therapy resulted in a reduction of pro-inflammatory biomarker expression in PICF from both the PIM and PI groups. Specifically, the PIM group showed a significant decrease in IL17-A and TNF-α, while the PI group exhibited a significant reduction in IL1-β, IL-6, and TNF-α. Additionally, there was a decreased tendency towards IFN-γ levels in the PI group, suggesting that the treatment may modulate this cytokine expression. Health implants were not included in the analysis, as the volume of PICF depends on the level of inflammation and PD [32], which probably would present a lower quantity in non-inflamed sites.
The observed significant reduction in IL-17A levels in patients with PIM after therapy suggests a positive modulation of the Th17 response, as this cytokine is involved in the differentiation of Th17 cells, osteoclast activation, and the recruitment of defense cells and pro-inflammatory cytokines such as IL1-β, IL-6, IL-8, G-CSF, GM-CSF, and TNF-α [33,34,35]. To the best of our knowledge, only one longitudinal study has assessed this cytokine in patients with PIM after therapy [36], also finding a significant reduction level. No prior studies have evaluated the effect of treatment on the modulation of IL-17A in PI. However, in our study, the reduction of IL-17A in the PI group did not reach statistical significance.
This study demonstrated a significant reduction in TNF-α levels in both the PIM and PI groups and a decrease in IL-1β levels specifically in the PI group after three months of therapy. These findings align with previous research, which also reported a significant reduction in TNF-α levels in the PICF of PIM patients following therapy [37]. Similarly, significant reductions in both TNF-α and IL-1β levels in the PICF of PI patients have been observed [38,39,40,41]. High levels of these biomarkers are typically found in the PICF of patients with PID [13,42,43,44,45,46], and they are considered predictive of disease progression [7]. Furthermore, our study revealed a significant positive correlation between TNF-α and IL-1β levels at baseline in the PI group, suggesting their coordinated activity in more inflamed sites. This positive correlation was not observed after therapy. The observed reduction in these biomarkers indicates a potential decrease in osteoclastic activity and inflammatory response [38,47].
The significant reduction in IL-6 levels in PI patients after therapy highlights the therapy’s positive impact on cytokine modulation. IL-6 is crucial in recruiting leukocytes, activating osteoclasts, and producing acute-phase proteins [48]. Consistent with our findings, previous studies have also reported decreased IL-6 levels in the PICF of PIM patients [37] and PI patients after therapy [41]. However, another study did not observe a statistically significant reduction in IL-6 levels six months after surgical therapy of PI, likely due to the initially low baseline levels of cytokine detection [49].
The tendency towards a significant reduction in IFN-γ levels in the PI group after therapy may suggest a potential association between IFN-γ and increased inflammation in PI. Our study also found a significant positive correlation between PD and IFN-γ at baseline in the PI group, with a negative correlation observed after therapy. This may indicate its role in increasing PD. This cytokine is known to promptly recruit macrophages, intensifying the inflammatory response [50] and accelerating periodontal disease progression [51]. However, it is important to note that the role of IFN-γ in the context of PID has been scarcely studied.
When comparing the PIM and PI groups at baseline, no statistically significant differences were found in the expression of any cytokine. This result suggests that once the inflammatory process begins, the expression of biomarkers remains similar regardless of the presence of bone loss. This finding is consistent with previous cross-sectional studies on Th17 response biomarker expression in the PICF of partially edentulous patients with PIM and PI [11,19].
IL-10 is a non-inflammatory cytokine that helps to suppress the inflammatory response and to protect the host [52,53]. In PIM and PI groups, IL-10 expression levels were below the detection limit, which can be attributed to the high pro-inflammatory activity present in both groups. The literature presents varied results: higher IL-10 expression in healthy patients compared to those with PI [38], higher IL-10 expression in the PI group compared to healthy controls [54], and no differences between groups [33,55].
The heat maps presented in Figure 4 and Figure 5 illustrate the correlations between cytokines in the two groups at different time points. Interestingly, in the PIM group, IL-17A showed a strong correlation with IL-6 before treatment, but this pattern was not maintained after therapy. Additionally, TNF-α in the PIM group did not show a significant positive correlation with any other cytokine. In contrast, in the PI group, TNF-α exhibited a significant positive correlation with GM-CSF, IL-17A, and IL-1β, which was no longer observed after treatment, suggesting a coordinated action of these cytokines during bone loss. Moreover, the correlation between GM-CSF and other cytokines was not observed in the PIM group but was identified in the PI group, with IL-17A, IL-1β, IL-6, and TNF-α. GM-CSF has the function of recruiting monocytes and dendritic cells in addition to promoting the increase of IL-6 and IL-23, which are involved in the differentiation of Th17 cells. The production of IL-23 enhances GM-CSF secretion, generating a positive feedback loop [56,57]. After treatment, these correlations were not observed, and the heat map reveals a negative tendency in the results. This finding may suggest the relevance of GM-CSF in the bone loss activity in peri-implant disease.
Our study found a higher prevalence of patients with PI when periodontal and peri-implant maintenance therapy (PIMT) was performed for more than one year. This result is consistent with findings from other studies [58,59,60,61,62] and highlights the importance of PIMT in preventing PI. The frequency of maintenance appointments must be established individually for each patient, based on their risk factors. However, a frequency of at least twice a year seems ideal for preventing PI [63,64]. Additionally, there was a notable trend of increased PI prevalence among patients with concomitant periodontitis at stage III. This condition is one of the factors most strongly associated with an increased risk of developing PI [4,59,65]. Although our findings were not statistically significant, this result may be attributed to the limited number of patients with periodontitis in the study.
This study observed a higher prevalence of PID in implants located in the posterior regions of the dental arches. This may be attributed to the greater difficulty in patients’ biofilm control of these areas, consistent with findings from previous studies [66,67,68,69,70]. However, there is no consensus on this issue, as some studies observed a higher prevalence of PI in implants located in the anterior region [69,70]. Additionally, there was a higher prevalence of PI in splinted prostheses, which can be explained by the increased complexity of biofilm removal in this type of prosthesis, making it more challenging for patients.
HE platform implants showed a higher prevalence of PI compared to CM platform implants. This difference can be attributed to the several advantages of CM over HE platforms, such as the internalization of the microgap between the abutment and implant, minimized micromovements in occlusal forces distribution, lower initial bone loss, improved bacterial sealing, and greater resistance to torque loss [71,72,73,74,75].
After therapy, there was a significant reduction in PD and the percentage of bleeding in the treated implants of the PIM and PI groups. However, most of the sites still exhibited bleeding, which may be related to the high plaque index observed. In the PI group, the plaque index was not significantly reduced, and in the PIM group, although it showed a significant reduction, it remained present in almost half of the evaluated implants. The persistence of bleeding after treatment has also been reported in previous studies [49,65,76,77,78]. This finding underscores the patient’s difficulty in effectively controlling biofilm on implants and their structures and the challenge in achieving the elimination of bleeding in all sites in the treatment of PID.
Patients in this study will continue to be monitored and receive PIMT. This follow-up is crucial to assess the long-term maintenance of the clinical and immunological outcomes observed. Given that the treatment effectively reduced pro-inflammatory cytokines involved in osteoclastogenesis, and considering that the surgical therapy protocol used for PI provided adequate access to the implant surface for decontamination, it is expected that crestal bone levels will be sustained and soft tissue inflammation will remain stable over extended follow-up periods, provided that patients stay compliant with the treatment.
This study presents certain limitations, such as the relatively small sample size and short follow-up period, which may restrict the generalizability of the findings. Future research with more extensive sampling and longer follow-up periods would provide more substantial evidence on the modulation of Th17-related cytokine expression and the clinical outcomes of peri-implant disease treatments. Therefore, the results should be interpreted with caution.

5. Conclusions

In conclusion, our study demonstrates that after three months of therapy, there was a significant reduction in the expression of cytokines in the peri-implant crevicular fluid of patients with peri-implant mucositis (IL-17A and TNF-α) and peri-implantitis (IL -1β, IL-6, and TNF-α). This finding indicates that peri-implant therapy can modulate important cytokines in exacerbating the inflammatory response and osteoclastogenesis.

Author Contributions

Conceptualization, C.M.d.S.F., M.K.S.T. and E.J.V.L.; methodology, L.T.d.C.G., C.M.d.S.F., M.K.S.T. and E.J.V.L.; validation, M.K.S.T., D.d.M.T. and E.J.V.L.; formal analysis, L.T.d.C.G., M.K.S.T., A.M.P.d.S. and E.J.V.L.; investigation, L.T.d.C.G. and G.S.T.N.; writing—original draft preparation, L.T.d.C.G.; writing—review and editing, L.T.d.C.G., A.M.P.d.S., G.S.T.N. and M.K.S.T.; visualization, L.T.d.C.G. and E.J.V.L.; supervision, M.K.S.T.; project administration, L.T.d.C.G., D.d.M.T. and M.K.S.T.; funding acquisition, M.K.S.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by CARLOS CHAGAS FILHO DE AMPARO FOUNDATION (FAPERJ), grant number 210.072/2018.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of PEDRO ERNESTO UNIVERSITY HOSPITAL (HUPE/UERJ) (protocol code 69156722.5.0000.5259, approved on 25 June 2023).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.

Acknowledgments

This study was carried out at the School of Dentistry of Rio de Janeiro State University. The authors thank all collaborators of this study.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Berglundh, T.; Armitage, G.; Araujo, M.G.; Avila-Ortiz, G.; Blanco, J.; Camargo, P.M.; Chen, S.; Cochran, D.; Derks, J.; Figuero, E.; et al. Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J. Clin. Periodontol. 2018, 45, 286–291. [Google Scholar] [CrossRef]
  2. Gargallo-Albiol, J.; Tavelli, L.; Barootchi, S.; Monje, A.; Wang, H.L. Clinical sequelae and patients’ perception of dental implant removal: A cross-sectional study. J. Periodontol. 2021, 92, 823–832. [Google Scholar] [CrossRef]
  3. Lee, C.T.; Huang, Y.W.; Zhu, L.; Weltman, R. Prevalences of peri-implantitis and peri-implant mucositis: Systematic review and meta-analysis. J. Dent. 2017, 62, 1–12. [Google Scholar] [CrossRef] [PubMed]
  4. Derks, J.; Schaller, D.; Håkansson, J.; Wennström, J.L.; Tomasi, C.; Berglundh, T. Peri-implantitis—Onset and pattern of progression. J. Clin. Periodontol. 2016, 43, 383–388. [Google Scholar] [CrossRef]
  5. Darby, I. Risk factors for periodontitis & peri-implantitis. Periodontol. 2000 2022, 90, 9–12. [Google Scholar] [CrossRef] [PubMed]
  6. Diaz, P.; Gonzalo, E.; Villagra, L.J.G.; Miegimolle, B.; Suarez, M.J. What is the prevalence of peri-implantitis? A systematic review and meta-analysis. BMC Oral Health 2022, 22, 449. [Google Scholar] [CrossRef] [PubMed]
  7. Chmielewski, M.; Pilloni, A. Current Molecular, Cellular and Genetic Aspects of Peri-Implantitis Disease: A Narrative Review. Dent. J. 2023, 11, 134. [Google Scholar] [CrossRef] [PubMed]
  8. Corrêa, M.G.; Pimentel, S.P.; Ribeiro, F.V.; Cirano, F.R.; Casati, M.Z. Host response and peri-implantitis. Braz. Oral Res. 2019, 33, e066. [Google Scholar] [CrossRef] [PubMed]
  9. Troen, B.R. Molecular mechanisms underlying osteoclast formation and activation. Exp. Gerontol. 2003, 38, 605–614. [Google Scholar] [CrossRef]
  10. Markou, E.; Eleana, B.; Lazaros, T.; Antonios, K. The influence of sex steroid hormones on gingiva of women. Open Dent. J. 2009, 5, 114–119. [Google Scholar] [CrossRef]
  11. Severino, V.O.; Beghini, M.; de Araújo, M.F.; de Melo, M.L.R.; Miguel, C.B.; Rodrigues, W.F.; Pereira, S.A.d.L. Expression of IL-6, IL-10, IL-17 and IL-33 in the peri-implant crevicular fluid of patients with peri-implant mucositis and peri-implantitis. Arch. Oral Biol. 2016, 72, 194–199. [Google Scholar] [CrossRef]
  12. Petković, A.B.; Matić, S.M.; Stamatović, N.V.; Vojvodić, D.V.; Todorović, T.M.; Lazić, Z.R.; Kozomara, R.J. Proinflammatory cytokines (IL-1beta and TNF-alpha) and chemokines (IL-8 and MIP-1alpha) as markers of peri-implant tissue condition. Int. J. Oral Maxillofac. Surg. 2010, 39, 478–485. [Google Scholar] [CrossRef]
  13. Faot, F.; Nascimento, G.G.; Bielemann, A.M.; Campão, T.D.; Leite, F.R.; Quirynen, M. Can peri-implant crevicular fluid assist in the diagnosis of peri-implantitis? A systematic review and meta-analysis. J. Periodontol. 2015, 865, 631–645. [Google Scholar] [CrossRef]
  14. Delucchi, F.; Canepa, C.; Canullo, L.; Pesce, P.; Isola, G.; Menini, M. Biomarkers from Peri-Implant Crevicular Fluid (PICF) as Predictors of Peri-Implant Bone Loss: A Systematic Review. Int. J. Mol. Sci. 2023, 24, 3202. [Google Scholar] [CrossRef] [PubMed]
  15. Askar, M. T helper subsets & regulatory T cells: Rethinking the paradigm in the clinical context of solid organ transplantation. Int. J. Immunogenet. 2014, 41, 185–194. [Google Scholar] [CrossRef] [PubMed]
  16. Iwakura, Y.; Nakae, S.; Saijo, S.; Ishigame, H. The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol. Rev. 2008, 226, 57–79. [Google Scholar] [CrossRef]
  17. Korn, T.; Bettelli, E.; Oukka, M.; Kuchroo, V.K. IL-17 and Th17 Cells. Annu. Rev. Immunol. 2009, 27, 485–517. [Google Scholar] [CrossRef] [PubMed]
  18. Giro, G.; Tebar, A.; Franco, L.; Racy, D.; Bastos, M.F.; Shibli, J.A. Treg and TH17 link to immune response in individuals with peri-implantitis: A preliminary report. Clin. Oral Investig. 2021, 25, 1291–1297. [Google Scholar] [CrossRef]
  19. Teixeira, M.K.S.; Lira-Junior, R.; Telles, D.M.; Lourenço, E.J.V.; Figueredo, C.M. Th17-related cytokines in mucositis: Is there any difference between peri-implantitis and periodontitis patients? Clin. Oral Implant. Res. 2017, 28, 816–822. [Google Scholar] [CrossRef]
  20. Heitz-Mayfield, L.J.A.; Salvi, G.E.; Mombelli, A.; Loup, P.J.; Heitz, F.; Kruger, E.; Lang, N.P. Supportive peri-implant therapy following anti-infective surgical peri-implantitis treatment: 5-year survival and success. Clin. Oral Implant. Res. 2018, 29, 1–6. [Google Scholar] [CrossRef]
  21. Schwarz, F.; Jepsen, S.; Obreja, K.; Galarraga-Vinueza, M.E.; Ramanauskaite, A. Surgical therapy of peri-implantitis. Periodontol. 2000 2022, 88, 145–181. [Google Scholar] [CrossRef] [PubMed]
  22. Verket, A.; Koldsland, O.C.; Bunaes, D.; Lie, S.A.; Romandini, M. Non-surgical therapy of peri-implant mucositis-Mechanical/physical approaches: A systematic review. J. Clin. Periodontol. 2023, 26, 135–145. [Google Scholar] [CrossRef] [PubMed]
  23. Ramanauskaite, A.; Daugela, P.; Juodzbalys, G. Treatment of peri-implantitis: Meta-analysis of findings in a systematic literature review and novel protocol proposal. Quintessence Int. 2016, 47, 379–393. [Google Scholar] [CrossRef]
  24. Dos Santos Martins, B.G.; Fernandes, J.C.H.; Martins, A.G.; de Moraes Castilho, R.; de Oliveira Fernandes, G.V. Surgical and Nonsurgical Treatment Protocols for Peri-implantitis: An Overview of Systematic Reviews. Int. J. Oral Maxillofac. Implant. 2022, 37, 660–676. [Google Scholar] [CrossRef] [PubMed]
  25. Ichioka, Y.; Virto, L.; Nuevo, P.; Gamonal, J.D.; Derks, J.; Larsson, L.; Sanz, M.; Berglundh, T. Decontamination of biofilm-contaminated implant surfaces: An in vitro evaluation. Clin. Oral Implant. Res. 2023, 34, 1058–1072. [Google Scholar] [CrossRef] [PubMed]
  26. Teixeira Neves, G.S.; Elangovan, G.; Teixeira, M.K.S.; Mello-Neto, J.M.; Tadakamadla, S.K.; Lourenço, E.J.V.; Telles, D.M.; Figueredo, C.M. Peri-Implant Surgical Treatment Downregulates the Expression of sTREM-1 and MMP-8 in Patients with Peri-Implantitis: A Prospective Study. Int. J. Environ. Res. Public Health 2022, 19, 3627. [Google Scholar] [CrossRef] [PubMed]
  27. Renvert, S.; Persson, G.R.; Pirih, F.Q.; Camargo, P.M. Peri-implant health, peri-implant mucositis, and peri-implantitis: Case definitions and diagnostic considerations. J. Periodontol. 2018, 89, 304–312. [Google Scholar] [CrossRef] [PubMed]
  28. Ainamo, J.; Bay, I. Problems and proposals for recording gingivitis and plaque. Int. Dent. J. 1975, 25, 229–235. [Google Scholar]
  29. Wassall, R.R.; Preshaw, P.M. Clinical and technical considerations in the analysis of gingival crevicular fluid. Periodontol. 2000 2016, 70, 65–79. [Google Scholar] [CrossRef] [PubMed]
  30. Lang, N.P.; Berglundh, T.; Heitz-Mayfield, L.J.; Pjetursson, B.E.; Salvi, G.E.; Sanz, M. Consensus statements and recommended clinical procedures regarding implant survival and complications. Int. J. Oral Maxillofac. Implant. 2004, 19, 150–154. [Google Scholar]
  31. Khoury, F.; Keeve, P.L.; Ramanauskaite, A.; Schwarz, F.; Koo, K.T.; Sculean, A.; Romanos, G. Surgical treatment of peri-implantitis—Consensus report of working group 4. Int. Dent. J. 2019, 69, 18–22. [Google Scholar] [CrossRef] [PubMed]
  32. Alassy, H.; Parachuru, P.; Wolff, L. Peri-Implantitis Diagnosis and Prognosis Using Biomarkers in Peri-Implant Crevicular Fluid: A Narrative Review. Diagnostics 2019, 9, 214. [Google Scholar] [CrossRef] [PubMed]
  33. Severino, V.O.; Napimoga, M.H.; de Lima Pereira, A.S. Expression of IL-6, IL-10, IL-17 and IL-8 in the peri-implant crevicular fluid of patients with peri-implantitis. Arch. Oral Biol. 2011, 56, 823–828. [Google Scholar] [CrossRef]
  34. de Araújo, M.F.; Filho, A.F.; da Silva, G.P.; de Melo, M.L.R.; Napimoga, M.H.; Rodrigues, D.B.R.; Alves, P.M.; Pereira, S.A.d.L. Evaluation of peri-implant mucosa: Clinical, histopathological and immunological aspects. Arch. Oral Biol. 2014, 59, 470–478. [Google Scholar] [CrossRef]
  35. Irie, K.; Azuma, T.; Tomofuji, T.; Yamamoto, T. Exploring the Role of IL-17A in Oral Dysbiosis-Associated Periodontitis and Its Correlation with Systemic Inflammatory Disease. Dent. J. 2023, 11, 194. [Google Scholar] [CrossRef]
  36. Kashefimehr, A.; Pourabbas, R.; Faramarzi, M.; Zarandi, A.; Moradi, A.; Tenenbaum, H.C.; Azarpazhooh, A. Effects of enamel matrix derivative on non-surgical management of peri-implant mucositis: A double-blind randomized clinical trial. Clin. Oral Investig. 2017, 21, 2379–2388. [Google Scholar] [CrossRef]
  37. Pourabbas, R.; Khorramdel, A.; Sadighi, M.; Kashefimehr, A.; Mousavi, S.A. Effect of photodynamic therapy as an adjunctive to mechanical debridement on the nonsurgical treatment of peri-implant mucositis: A randomized controlled clinical trial. Dent. Res. J. (Isfahan) 2023, 20, 1. [Google Scholar] [CrossRef]
  38. Duarte, P.M.; de Mendonça, A.C.; Máximo, M.B.; Santos, V.R.; Bastos, M.F.; Nociti, F.H. Effect of anti-infective mechanical therapy on clinical parameters and cytokine levels in human peri-implant diseases. J. Periodontol. 2009, 80, 234–243. [Google Scholar] [CrossRef] [PubMed]
  39. de Mendonça, A.C.; Santos, V.R.; César-Neto, J.B.; Duarte, P.M. Tumor necrosis factor-alpha levels after surgical anti-infective mechanical therapy for peri-implantitis: A 12-month follow-up. J. Periodontol. 2009, 80, 693–699. [Google Scholar] [CrossRef] [PubMed]
  40. Bassetti, M.; Schär, D.; Wicki, B.; Eick, S.; Ramseier, C.A.; Arweiler, N.B.; Sculean, A.; Salvi, G.E. Anti-infective therapy of peri-implantitis with adjunctive local drug delivery or photodynamic therapy: 12-month outcomes of a randomized controlled clinical trial. Clin. Oral Implant. Res. 2014, 25, 279–287. [Google Scholar] [CrossRef] [PubMed]
  41. Elsadek, M.F. Effectiveness of two photosensitizer-mediated photodynamic therapy for treating moderate peri-implant infections in type-II diabetes mellitus patients: A randomized clinical trial. Photodiagnosis Photodyn. Ther. 2023, 43, 103643. [Google Scholar] [CrossRef]
  42. Ata-Ali, J.; Flichy-Fernández, A.J.; Alegre-Domingo, T.; Ata-Ali, F.; Palacio, J.; Peñarrocha-Diago, M. Clinical, microbiological, and immunological aspects of healthy versus peri-implantitis tissue in full arch reconstruction patients: A prospective cross-sectional study. BMC Oral Health 2015, 15, 43. [Google Scholar] [CrossRef] [PubMed]
  43. Zani, S.R.; Moss, K.; Shibli, J.A.; Teixeira, E.R.; de Oliveira Mairink, R.; Onuma, T.; Feres, M.; Teles, R.P. Peri-implant crevicular fluid biomarkers as discriminants of peri-implant health and disease. J. Clin. Periodontol. 2016, 43, 825–832. [Google Scholar] [CrossRef]
  44. Bhavsar, I.; Miller, C.S.; Ebersole, J.L.; Dawson, D.R., 3rd; Thompson, K.L.; Al-Sabbagh, M. Biological response to peri-implantitis treatment. J. Periodontal. Res. 2019, 54, 720–728. [Google Scholar] [CrossRef]
  45. Hentenaar, D.F.M.; De Waal, Y.C.M.; Vissink, A.; Van Winkelhoff, A.J.; Meijer, H.J.; Liefers, S.C.; Kroese, F.G.; Raghoebar, G.M. Biomarker levels in peri-implant crevicular fluid of healthy implants, untreated and non-surgically treated implants with peri-implantitis. J. Clin. Periodontol. 2021, 48, 590–601. [Google Scholar] [CrossRef]
  46. Song, L.; Jiang, J.; Li, J.; Zhou, C.; Chen, Y.; Lu, H.; He, F. The Characteristics of Microbiome and Cytokines in Healthy Implants and Peri-Implantitis of the Same Individuals. J. Clin. Med. 2022, 11, 5817. [Google Scholar] [CrossRef]
  47. Lumbikananda, S.; Srithanyarat, S.S.; Mattheos, N.; Osathanon, T. Oral Fluid Biomarkers for Peri-Implantitis: A Scoping Review. Int. Dent. J. 2024, 74, 387–402. [Google Scholar] [CrossRef]
  48. Tanaka, T.; Narazaki, M.; Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol. 2014, 6, a016295. [Google Scholar] [CrossRef] [PubMed]
  49. Luengo, F.; Solonko, M.; Sanz-Esporrín, J.; Sanz-Sánchez, I.; Herrera, D.; Sanz, M. Clinical, Microbiological, and Biochemical Impact of the Surgical Treatment of Peri-Implantitis-A Prospective Case Series. J. Clin. Med. 2022, 11, 4699. [Google Scholar] [CrossRef]
  50. Nagy, E.; Lei, Y.; Martínez-Martínez, E.; Body, S.C.; Schlotter, F.; Creager, M.; Assmann, A.; Khabbaz, K.; Libby, P.; Hansson, G.K.; et al. Interferon-γ Released by Activated CD8+ T Lymphocytes Impairs the Calcium Resorption Potential of Osteoclasts in Calcified Human Aortic Valves. Am. J. Pathol. 2017, 187, 1413–1425. [Google Scholar] [CrossRef] [PubMed]
  51. Danielsen, A.K.; Damgaard, C.; Massarenti, L.; Østrup, P.; Riis Hansen, P.; Holmstrup, P.; Nielsen, C.H. B-cell cytokine responses to Porphyromonas gingivalis in patients with periodontitis and healthy controls. J. Periodontol. 2023, 94, 997–1007. [Google Scholar] [CrossRef] [PubMed]
  52. Iyer, S.S.; Cheng, G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit. Rev. Immunol. 2012, 32, 23–63. [Google Scholar] [CrossRef] [PubMed]
  53. Abbas, A.K.; Pillai, S.; Lichtman, A.H. Imunologia Celular e Molecular, 9th ed.; Elsevier: Rio de Janeiro, Brazil, 2019; pp. 856–857. [Google Scholar]
  54. Güncü, G.N.; Akman, A.C.; Günday, S.; Yamalık, N.; Berker, E. Effect of inflammation on cytokine levels and bone remodelling markers in peri-implant sulcus fluid: A preliminary report. Cytokine 2012, 59, 313–316. [Google Scholar] [CrossRef] [PubMed]
  55. Fonseca, F.J.; Moraes Junior, M.; Lourenço, E.J.; Teles, D.M.; Figueredo, C.M. Cytokines expression in saliva and peri-implant crevicular fluid of patients with peri-implant disease. Clin. Oral Implant. Res. 2014, 25, 68–72. [Google Scholar] [CrossRef] [PubMed]
  56. Huang, N.; Dong, H.; Luo, Y.; Shao, B. Th17 Cells in Periodontitis and Its Regulation by A20. Front. Immunol. 2021, 12, 742925. [Google Scholar] [CrossRef] [PubMed]
  57. El-Behi, M.; Ciric, B.; Dai, H.; Yan, Y.; Cullimore, M.; Safavi, F.; Zhang, G.X.; Dittel, B.N.; Rostami, A. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat. Immunol. 2011, 12, 568–575. [Google Scholar] [CrossRef]
  58. Gay, I.C.; Tran, D.T.; Weltman, R.; Parthasarathy, K.; Diaz-Rodriguez, J.; Walji, M.; Fu, Y.; Friedman, L. Role of supportive maintenance therapy on implant survival: A university-based 17 years retrospective analysis. Int. J. Dent. Hyg. 2016, 14, 267–271. [Google Scholar] [CrossRef] [PubMed]
  59. Monje, A.; Wang, H.L.; Nart, J. Association of Preventive Maintenance Therapy Compliance and Peri-Implant Diseases: A Cross-Sectional Study. J. Periodontol. 2017, 88, 1030–1041. [Google Scholar] [CrossRef] [PubMed]
  60. Frisch, E.; Vach, K.; Ratka-Krueger, P. Impact of supportive implant therapy on peri-implant diseases: A retrospective 7-year study. J. Clin. Periodontol. 2020, 47, 101–109. [Google Scholar] [CrossRef] [PubMed]
  61. Astolfi, V.; Ríos-Carrasco, B.; Gil-Mur, F.J.; Ríos-Santos, J.V.; Bullón, B.; Herrero-Climent, M.; Bullón, P. Incidence of Peri-Implantitis and Relationship with Different Conditions: A Retrospective Study. Int. J. Environ. Res. Public Health 2022, 19, 4147. [Google Scholar] [CrossRef]
  62. Costa, F.O.; Costa, A.M.; Ferreira, S.D.; Lima, R.P.E.; Pereira, G.H.M.; Cyrino, R.M.; Oliveira, A.M.S.D.; Oliveira, P.A.D.; Cota, L.O.M. Long-term impact of patients’ compliance to peri-implant maintenance therapy on the incidence of peri-implant diseases: An 11-year prospective follow-up clinical study. Clin. Implant Dent. Relat. Res. 2023, 25, 303–312. [Google Scholar] [CrossRef] [PubMed]
  63. Rösing, C.K.; Fiorini, T.; Haas, A.N.; Muniz, F.W.M.G.; Oppermann, R.V.; Susin, C. The impact of maintenance on peri-implant health. Braz. Oral Res. 2019, 33, e074. [Google Scholar] [CrossRef] [PubMed]
  64. Leone, F.D.; Blasi, G.; Amerio, E.; Valles, C.; Nart, J.; Monje, A. Influence of the level of compliance with preventive maintenance therapy upon the prevalence of peri-implant diseases. J. Periodontol. 2024, 95, 40–49. [Google Scholar] [CrossRef] [PubMed]
  65. Schwarz, F.; Derks, J.; Monje, A.; Wang, H.L. Peri-implantitis. J. Periodontol. 2018, 89, 267–290. [Google Scholar] [CrossRef] [PubMed]
  66. Jia, P.; Tang, Y.; Niu, L.; Qiu, L. Clinical and radiographic outcomes of a combined surgery approach to treat peri-implantitis. Int. J. Oral Maxillofac. Surg. 2024, 53, 333–342. [Google Scholar] [CrossRef]
  67. Derks, J.; Ortiz-Vigón, A.; Guerrero, A.; Donati, M.; Bressan, E.; Ghensi, P.; Schaller, D.; Tomasi, C.; Karlsson, K.; Abrahamsson, I.; et al. Reconstructive surgical therapy of peri-implantitis: A multicenter randomized controlled clinical trial. Clin. Oral Implant. Res. 2022, 33, 921–944. [Google Scholar] [CrossRef] [PubMed]
  68. Romandini, M.; Laforí, A.; Pedrinaci, I.; Baima, G.; Ferrarotti, F.; Lima, C.; Holtzman, L.P.; Aimetti, M.; Cordaro, L.; Sanz, M. Effect of sub-marginal instrumentation before surgical treatment of peri-implantitis: A multi-centre randomized clinical trial. J. Clin. Periodontol. 2022, 49, 1334–1345. [Google Scholar] [CrossRef]
  69. Moraschini, V.; Kischinhevsky, I.C.C.; Sartoretto, S.C.; de Almeida Barros Mourão, C.F.; Sculean, A.; Calasans-Maia, M.D.; Shibli, J.A. Does implant location influence the risk of peri-implantitis? Periodontol. 2000 2022, 90, 224–235. [Google Scholar] [CrossRef]
  70. Sun, J.S.; Liu, K.C.; Hung, M.C.; Lin, H.Y.; Chuang, S.L.; Lin, P.J.; Chang, J.Z. A cross-sectional study for prevalence and risk factors of peri-implant marginal bone loss. J. Prosthet. Dent. 2023, in press. [Google Scholar] [CrossRef] [PubMed]
  71. Koo, K.T.; Lee, E.J.; Kim, J.Y.; Seol, Y.J.; Han, J.S.; Kim, T.I.; Lee, Y.M.; Ku, Y.; Wikesjö, U.M.; Rhyu, I.C. The effect of internal versus external abutment connection modes on crestal bone changes around dental implants: A radiographic analysis. J. Periodontol. 2012, 83, 1104–1109. [Google Scholar] [CrossRef] [PubMed]
  72. Machado, L.S.; Bonfante, E.A.; Anchieta, R.B.; Yamaguchi, S.; Coelho, P.G. Implant-abutment connection designs for anterior crowns: Reliability and failure modes. Implant Dent. 2013, 22, 540–545. [Google Scholar] [CrossRef]
  73. Schmitt, C.M.; Nogueira-Filho, G.; Tenenbaum, H.C.; Lai, J.Y.; Brito, C.; Döring, H.; Nonhoff, J. Performance of conical abutment (Morse Taper) connection implants: A systematic review. J. Biomed. Mater. Res. A 2014, 102, 552–574. [Google Scholar] [CrossRef] [PubMed]
  74. Macedo, J.P.; Pereira, J.; Vahey, B.R.; Henriques, B.; Benfatti, C.A.M.; Magini, R.S.; López-López, J.; Souza, J.C.M. Morse taper dental implants and platform switching: The new paradigm in oral implantology. Eur. J. Dent. 2016, 10, 148–154. [Google Scholar] [CrossRef] [PubMed]
  75. Teixeira, M.K.S.; de Moraes Rego, M.R.; da Silva, M.F.T.; Lourenço, E.J.V.; Figueredo, C.M.; Telles, D.M. Bacterial Profile and Radiographic Analysis Around Osseointegrated Implants With Morse Taper and External Hexagon Connections: Split-Mouth Model. J. Oral Implantol. 2019, 45, 469–473. [Google Scholar] [CrossRef]
  76. Heitz-Mayfield, L.J.A.; Salvi, G.E.; Mombelli, A.; Faddy, M.; Lang, N.P. Anti-infective surgical therapy of peri-implantitis. A 12-month prospective clinical study. Clin. Oral Implant. Res. 2012, 23, 205–210. [Google Scholar] [CrossRef] [PubMed]
  77. Carcuac, O.; Derks, J.; Charalampakis, G.; Abrahamsson, I.; Wennström, J.; Berglundh, T. Adjunctive Systemic and Local Antimicrobial Therapy in the Surgical Treatment of Peri-implantitis: A Randomized Controlled Clinical Trial. J. Dent. Res. 2016, 95, 50–57. [Google Scholar] [CrossRef] [PubMed]
  78. Carcuac, O.; Derks, J.; Abrahamsson, I.; Wennström, J.L.; Petzold, M.; Berglundh, T. Surgical treatment of peri-implantitis: 3-year results from a randomized controlled clinical trial. J. Clin. Periodontol. 2017, 44, 1294–1303. [Google Scholar] [CrossRef]
Jcm 14 00340 g001
Figure 1. Illustration of the functions of cytokines related to Th17 cells in peri-implant diseases. The left side represents peri-implant mucositis, characterized by biofilm-induced inflammation without bone loss. The right side illustrates peri-implantitis, with biofilm-induced inflammation, bone loss, and the presence of osteoclasts. The cytokines evaluated in this study are highlighted in the illustration with their functions in the inflammatory response. A bidirectional arrow between GM-CSF and IL-23 indicates the positive feedback loop between these cytokines.
Figure 1. Illustration of the functions of cytokines related to Th17 cells in peri-implant diseases. The left side represents peri-implant mucositis, characterized by biofilm-induced inflammation without bone loss. The right side illustrates peri-implantitis, with biofilm-induced inflammation, bone loss, and the presence of osteoclasts. The cytokines evaluated in this study are highlighted in the illustration with their functions in the inflammatory response. A bidirectional arrow between GM-CSF and IL-23 indicates the positive feedback loop between these cytokines.
Jcm 14 00340 g001
Jcm 14 00340 g002
Figure 2. (a–j) Representation of biomarker expression results before and after therapy. PIM—Peri-implant mucositis; PI—Peri-implantitis. Results are presented in boxplots, with the left side referring to the PIM group (before and after therapy) and the right side referring to the PI group (before and after therapy). The * and circles represent outliers: * indicates values two times the standard deviation (SD), while circles indicate values three times the SD. When the p-value was < 0.05, the values were included in the figure. The boxplot graphs were created with the SPSS program (version 24).
Figure 2. (a–j) Representation of biomarker expression results before and after therapy. PIM—Peri-implant mucositis; PI—Peri-implantitis. Results are presented in boxplots, with the left side referring to the PIM group (before and after therapy) and the right side referring to the PI group (before and after therapy). The * and circles represent outliers: * indicates values two times the standard deviation (SD), while circles indicate values three times the SD. When the p-value was < 0.05, the values were included in the figure. The boxplot graphs were created with the SPSS program (version 24).
Jcm 14 00340 g002
Jcm 14 00340 g003
Figure 3. Correlation between cytokines and clinical data in PIM group. PD: probing depth; CAL: clinical attachment level; % PID: plaque index; %BoP: bleeding on probing. The correlation coefficient was obtained by Spearman’s correlation test. *: p < 0.05 level.
Figure 3. Correlation between cytokines and clinical data in PIM group. PD: probing depth; CAL: clinical attachment level; % PID: plaque index; %BoP: bleeding on probing. The correlation coefficient was obtained by Spearman’s correlation test. *: p < 0.05 level.
Jcm 14 00340 g003
Jcm 14 00340 g004
Figure 4. Correlation between cytokines and clinical data in the PI group. PD: probing depth; CAL: clinical attachment level; % PID: plaque index; %BoP: bleeding on probing. The correlation coefficient obtained by Spearman’s correlation test. **: p < 0.01; *: p < 0.05 level.
Figure 4. Correlation between cytokines and clinical data in the PI group. PD: probing depth; CAL: clinical attachment level; % PID: plaque index; %BoP: bleeding on probing. The correlation coefficient obtained by Spearman’s correlation test. **: p < 0.01; *: p < 0.05 level.
Jcm 14 00340 g004
Jcm 14 00340 g005
Figure 5. Correlation between cytokines in the PIM group in T0 (a) and T1 (b). The correlation coefficient was obtained by Pearson’s correlation test. **: p < 0.01; *: p < 0.05.
Figure 5. Correlation between cytokines in the PIM group in T0 (a) and T1 (b). The correlation coefficient was obtained by Pearson’s correlation test. **: p < 0.01; *: p < 0.05.
Jcm 14 00340 g005
Jcm 14 00340 g006
Figure 6. Correlation between cytokines in PI group in T0 (a) and T1 (b). The correlation coefficient was obtained by Pearson’s correlation test. **: p < 0.01; *: p < 0.05.
Figure 6. Correlation between cytokines in PI group in T0 (a) and T1 (b). The correlation coefficient was obtained by Pearson’s correlation test. **: p < 0.01; *: p < 0.05.
Jcm 14 00340 g006
Table 1. Demographic data at the baseline.
Table 1. Demographic data at the baseline.
TotalPeri-Implant
Mucositis		Peri-Implantitisp Value
Participants37 (100%)20 (54.05%)17 (45.95%)0.622
Gender
Male15 (40.54%)7 (46.66%)8 (53.34%)0.457
Female22 (59.46%)13 (59.1%)9 (40.9%)0.457
Age59.14 (±10.37)58.65 (±11.62)59.70 (±9.01)0.219
Periodontal Classification in Concomitant Periodontitis8 (100%)2 (25%)6 (75%)0.157
Generalized Stage II Grade A1 (12.5%)1 (100%)0 (0%)-
Generalized Stage III Grade A6 (75%)1 (16.67%)5 (83.33%)0.197
Generalized Stage III Grade B1 (12.5%)0 (0%)1 (100%)-
Last PIMT
Less than a year8 (21.62%)6 (75%)2 (2%)0.157
Between 1 and 2 years17 (45.95%)9 (52.94%)8 (47.06%)0.808
More than 2 years12 (32.43%)5 (41.67%)7 (58.33%)0.564
PIMT—Periodontal and peri-implant maintenance therapy. Outcomes were presented as numbers and percentages. Age was presented as mean and standard deviation (±). p-value was evaluated using the Chi-square statistical test.
Table 2. Clinical outcomes of PIM group in baseline and T1.
Table 2. Clinical outcomes of PIM group in baseline and T1.
BaselineT1p Value
PD (mm)3.90 (±1.34)3.27 (±1.19)0.001
CAL (mm)2.41 (±1.37)1.50 (±1.31)<0.001
% PId71.43 (±45.58)46.43 (±50.32)0.003
% BoP100 (±0.00)51.79 (±50.42)<0.001
PD—Probing depth; CAL—Clinical attachment level; % PId—percentage of plaque index; % BoP—percentage of bleeding on probing. Outcomes were presented as mean and standard deviation (±). p-value was evaluated using the Wilcoxon statistical test.
Table 3. Clinical outcomes of PI group in baseline and T1.
Table 3. Clinical outcomes of PI group in baseline and T1.
BaselineT1p Value
PD (mm)5.29 (±1.74)3.00 (±1.00)<0.001
CAL (mm)4.32 (±1.78)3.00 (±1.80)0.004
% PId65.63 (±48.25)46.88 (±50.70)0.083
% BoP100 (±0.00)56.25 (±50.40)<0.001
PD—Probing depth; CAL—Clinical attachment level; % PId—percentage of plaque index; % BoP—percentage of bleeding on probing. Outcomes were presented as mean and standard deviation (±). p-value was evaluated using the Wilcoxon statistical test.
Table 4. Descriptive data of implants.
Table 4. Descriptive data of implants.
Total Number of Implants
(n = 88)		Implants of PIM Group
(n = 56)		Implants of PI Group
(n = 32)		p-Value
Arch, n (%)Upper40 (45.45%)30 (34.09%)10 (11.36%)0.002
Lower48 (54.55%)26 (29.55%)22 (25%)0.564
p-value0.3940.5930.34
Position, n (%)Anterior (canine-canine)13 (14.77%)8 (14.28%)5 (15.62%)0.405
Posterior75 (85.23%)48 (85.72%)27 (84.38%)0.015
p-value<0.001<0.001<0.001
Type of prosthetic platformMorse Taper40 (45.45%)32 (57.14%)8 (25%)<0.001
External Hexagon48 (54.55%)24 (42.86%)24 (75%)1.000
p-value0.3940.2850.005
Cemented or screwedCemented40 (45.45%)27 (48.21%)13 (40.62%)0.027
Screwed48 (54.55%)29 (51.79%)19 (59.38%)0.149
p-value0.3940.7890.289
Splinted or non-splintedSplinted32 (36.37%)9 (16.08%)23 (71.88%)0.013
Non-splinted56 (63.63%)47 (83.92%)9 (28.12%)<0.001
p-value0.011<0.0010.013
Data presented as number of implants and respective percentage. p-value was evaluated using the Chi-square statistical test.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Gonçalves, L.T.d.C.; Neves, G.S.T.; da Silva, A.M.P.; Telles, D.d.M.; Figueredo, C.M.d.S.; Lourenço, E.J.V.; Teixeira, M.K.S. The Effect of Peri-Implant Therapy on the Expression of Th17-Related Cytokines in Patients with Peri-Implant Mucositis and Peri-Implantitis: A Prospective Longitudinal Study. J. Clin. Med. 2025, 14, 340. https://doi.org/10.3390/jcm14020340

AMA Style

Gonçalves LTdC, Neves GST, da Silva AMP, Telles DdM, Figueredo CMdS, Lourenço EJV, Teixeira MKS. The Effect of Peri-Implant Therapy on the Expression of Th17-Related Cytokines in Patients with Peri-Implant Mucositis and Peri-Implantitis: A Prospective Longitudinal Study. Journal of Clinical Medicine. 2025; 14(2):340. https://doi.org/10.3390/jcm14020340

Chicago/Turabian Style

Gonçalves, Líssya Tomaz da Costa, Glaucia Schuindt Teixeira Neves, Alexandre Marques Paes da Silva, Daniel de Moraes Telles, Carlos Marcelo da Silva Figueredo, Eduardo José Veras Lourenço, and Mayla Kezy Silva Teixeira. 2025. "The Effect of Peri-Implant Therapy on the Expression of Th17-Related Cytokines in Patients with Peri-Implant Mucositis and Peri-Implantitis: A Prospective Longitudinal Study" Journal of Clinical Medicine 14, no. 2: 340. https://doi.org/10.3390/jcm14020340

APA Style

Gonçalves, L. T. d. C., Neves, G. S. T., da Silva, A. M. P., Telles, D. d. M., Figueredo, C. M. d. S., Lourenço, E. J. V., & Teixeira, M. K. S. (2025). The Effect of Peri-Implant Therapy on the Expression of Th17-Related Cytokines in Patients with Peri-Implant Mucositis and Peri-Implantitis: A Prospective Longitudinal Study. Journal of Clinical Medicine, 14(2), 340. https://doi.org/10.3390/jcm14020340

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop