Macrophage polarization in peri-implantitis lesions

Abstract

Objectives: To immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites.

Materials and methods: A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e., bleeding on probing with or without suppuration, probing depths ≥ 6 mm, and radiographic marginal bone loss ≥ 3 mm) were included. The severity of peri-implantitis was classified according to established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses.

Results: Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI 11.4-17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI 5.9-9.4) and 5.22% (95% CI 3.8-6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI 1-12-1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values.

Conclusion: The present immunohistochemical analysis suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis sites, which could possibly play a critical role in disease progression.

Clinical relevance: Macrophages have critical functions to establish homeostasis and disease. Bacteria might induce oral dysbiosis unbalancing the host's immunological response and triggering inflammation around dental implants. M1/M2 status could possibly reveal peri-implantitis' underlying pathogenesis.

Keywords: Biopsy; Dental implant; Immunohistochemistry; Macrophage polarization; Peri-implantitis.

Fig. 1

Distribution of a defect morphology [22] and b bar diagram depicting M1/M2 expression (%) at slight (n = 6), moderate (n = 6), and advanced (n = 6) peri-implantitis cases [19]. *p < 0.05, statistically significant

Fig. 2

a Peri-implantitis histological sections depicting immunohistochemical markers for CD68, CD80, and CD206 (200x). b Bar diagram representing the mean proportions (%) expressed per each immunohistochemical marker (i.e., CD68, CD80, and CD206) at the histological sections

Fig. 3

Linear regression plots to represent the relationship between CD68 (%) expression and a PD and b BOP % values, M1 (%) expression, and c PD and d BOP % values, M2 (%) expression, and e PD and f BOP % values and M1/M2 ratio and g PD, and h BOP % values. *p < 0.05 considered for statistical significance