Clinical Severity, Pre- and Post-Explantation Cytokine Profile and SEM/EDX-Defined Corrosion-Related Findings in Advanced Peri-Implantitis: Preliminary Results from the PERI-EDU Prospective Exploratory Clinical Study

PERI-EDU Research

Advanced Peri-Implantitis, Systemic Cytokines and Implant Corrosion: Preliminary Results from the PERI-EDU Study

A prospective exploratory clinical study combined clinical examination, CBCT-based assessment of bone loss, paired blood sampling and SEM/EDX analysis of explanted implants to investigate how severe peri-implantitis may connect local tissue destruction with systemic inflammation and corrosion-related surface changes.

Journal of Functional Biomaterials (2026), 17, 395  |  13 patients  |  Blood sampling before and 4 weeks after explantation  |  Open-access article
Main message: circulating IL-6 showed the strongest and most consistent association with clinical and radiographic disease severity. Implant removal was not followed by a uniform reduction in systemic cytokines after four weeks. Corrosion-related findings were not associated with higher cytokine levels at baseline, although an exploratory subgroup analysis suggested a different post-explantation TNF-α trajectory.

Why was the study performed?

Peri-implantitis is usually assessed as a local inflammatory disease, but advanced cases may also involve measurable systemic immune-inflammatory changes. At the same time, the diseased oral environment can alter the protective oxide layer of titanium implants. Biofilm, low pH, inflammation, mechanical wear and tribocorrosion may contribute to surface damage and the release of titanium-related products.

Previous studies have often investigated clinical severity, systemic inflammation or implant-surface alterations separately. The PERI-EDU study brought these elements together in the same patients to explore whether the severity of advanced peri-implantitis is reflected in circulating cytokines and whether SEM/EDX-defined corrosion-related findings are connected with cytokine behavior before and after implant removal.

Study design

13

Patients

Adults with active, advanced peri-implantitis clinically indicated for implant explantation.

4

Implant surfaces

Probing depth and CBCT-based bone loss were assessed at buccal, lingual/palatal, mesial and distal sites.

4 weeks

Follow-up

Peripheral blood was collected before explantation and again four weeks after implant removal.

Flow diagram showing screening, eligibility, explantation, follow-up and final analysis in the PERI-EDU study
Figure 1. Participant flow: 28 patients were screened, 19 underwent clinical and CBCT assessment, and 13 were included in the integrated analysis. Reproduced from the open-access article under CC BY 4.0.

The laboratory panel included IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF-α, high-sensitivity C-reactive protein (hsCRP) and fibrinogen. After explantation, implant surfaces were evaluated using scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM/EDX).

CBCT assessment of peri-implant bone loss showing bone defect depth and total implant length
Figure 2. CBCT-based measurement of peri-implant bone loss as the relationship between bone-defect depth and total implant length. Reproduced under CC BY 4.0.

Key findings

1. IL-6 tracked the severity of advanced peri-implantitis

IL-6 was strongly associated with both clinical and radiographic severity. Higher circulating IL-6 corresponded to greater mean and maximum probing depth, a larger number of surfaces with probing depth of at least 8 mm, greater mean and maximum bone loss, and more surfaces with at least 80% bone loss. These associations remained significant after correction for multiple testing.

Severity measureAssociation with baseline IL-6 (Spearman rho)
Mean probing depth0.859
Surfaces with probing depth ≥8 mm0.835
Maximum probing depth0.831
Surfaces with bone loss ≥80%0.823
Mean bone loss0.798
Maximum bone loss0.742

All IL-6 associations shown above remained statistically significant after Benjamini-Hochberg correction. Because this was a small exploratory study, effect estimates require confirmation in larger cohorts.

2. Cytokines did not uniformly decrease after explantation

Four weeks after implant removal, the study did not identify a uniform, statistically significant reduction across the measured cytokines, hsCRP or fibrinogen. This finding suggests that systemic inflammatory activity may persist beyond local surgical treatment or may partly reflect broader host-related inflammatory susceptibility.

Intraoperative view after flap elevation around an implant affected by advanced peri-implantitis
Figure 3. Intraoperative view after flap elevation around the failed implant. Reproduced under CC BY 4.0.
Peri-implant defect after implant removal and curettage
Figure 4. Post-explantation peri-implant defect after implant removal and curettage. Reproduced under CC BY 4.0.

3. Corrosion-related findings generated a new hypothesis

SEM/EDX-defined corrosion-related findings were present in five of the thirteen explanted implants. They were not associated with greater baseline clinical severity or higher baseline IL-6 or TNF-α. However, the post-explantation TNF-α pattern differed between exploratory subgroups: the median change was +0.90 pg/mL in the corrosion-related group and −1.16 pg/mL in the group without evident corrosion-related findings. TNF-α increased in four of five patients with corrosion-related findings and decreased in seven of eight patients without such findings.

SEM micrographs of explanted implants without evident corrosion-related findings
Figure 5. Representative SEM micrographs without evident corrosion-related findings. Reproduced under CC BY 4.0.
SEM images showing corrosion-related cracks, coating delamination and surface alterations on explanted implants
Figure 6. Representative SEM images illustrating corrosion-related surface findings. Reproduced under CC BY 4.0.

How should the findings be interpreted?

The results support the view that advanced peri-implantitis may have a measurable systemic immune-inflammatory component. Among the markers studied, IL-6 appears to be a promising indicator of inflammatory burden because it was associated with both soft-tissue findings and radiographic bone destruction. In contrast, hsCRP and fibrinogen did not show the same relationship in this cohort.

The observed TNF-α trajectory in relation to corrosion-related findings is hypothesis-generating rather than conclusive. The study was preliminary, included only 13 patients, had no healthy or disease-control group, and used a short follow-up period. Larger controlled studies with longer observation, paired serum and peri-implant crevicular-fluid measurements, tissue-level immune profiling and quantitative analysis of titanium particles or ions are needed.

Clinical perspective: the study does not establish IL-6 as a standalone diagnostic test and does not show that corrosion causes peri-implantitis. Diagnosis and treatment decisions must remain based on the complete clinical and radiographic assessment. The findings identify biological signals that deserve further investigation.

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Reference: Dominiak M, Baranowska A, Matys J, et al. Clinical Severity, Pre- and Post-Explantation Cytokine Profile and SEM/EDX-Defined Corrosion-Related Findings in Advanced Peri-Implantitis: Preliminary Results from the PERI-EDU Prospective Exploratory Clinical Study. Journal of Functional Biomaterials. 2026;17:395. https://doi.org/10.3390/jfb17080395