Diagnostic value of VEGF in peri-implantitis and its correlation with titanium particles: A controlled clinical study

Mia Rakic; Luigi Canullo; Sandro Radovanovic; Zoran Tatic; Milena Radunovic; Assem Souedain; Pierre Weiss; Xavier Struillou; Danilo Vojvodic

doi:10.1016/j.dental.2023.10.003

Diagnostic value of VEGF in peri-implantitis and its correlation with titanium particles: A controlled clinical study

Dent Mater. 2024 Jan;40(1):28-36. doi: 10.1016/j.dental.2023.10.003. Epub 2023 Oct 19.

Authors

Mia Rakic¹, Luigi Canullo², Sandro Radovanovic³, Zoran Tatic⁴, Milena Radunovic⁵, Assem Souedain⁶, Pierre Weiss⁷, Xavier Struillou⁸, Danilo Vojvodic⁹

Affiliations

¹ ETEP (Etiology and Therapy of Periodontal Diseases) Research Group, University Complutense of Madrid, Madrid, Spain. Electronic address: miarakic@ucm.es.
² Department of Surgical Sciences (DISC), University of Genoa, Genova, Italy; Department of Periodontology, University of Bern, Switzerland.
³ Faculty of Organizational Sciences, University of Belgrade, Belgrade, Serbia; Department for Oral Implantology, Military Medical Academy, Belgrade, Serbia.
⁴ Department for Oral Implantology, Military Medical Academy, Belgrade, Serbia.
⁵ Department of Oral Microbiology, Faculty of Dental Medicine, University of Belgrade, Belgrade, Serbia.
⁶ Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, University of Nantes, Department of Periodontology, Faculty of Dental Surgery, France.
⁷ Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, University of Nantes, France.
⁸ Department of Periodontology, Faculty of Dental Surgery, University of Nantes, France; Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, University of Nantes, France.
⁹ Institute for Experimental Medicine, Military Medical Academy, Belgrade, Serbia.

PMID: 37865576
DOI: 10.1016/j.dental.2023.10.003

Abstract

Objectives: VEGF is prototypic marker of neovascularization, repeatedly proposed as intrinsic characteristic of peri-implantitis. This study aimed to assess pattern of VEGF in peri-implantitis, its correlation with titanium particles (TPs) and capacity as respective biomarker.

Material and methods: Pathological specificity of VEGF was assessed in peri-implant granulations using immunohistochemistry, periodontal granulations represented Ti-free positive controls. VEGF was correlated to TPs, identified using scanning electron microscopy coupled with dispersive x-ray spectrometry. Diagnostic accuracy, sensitivity and specificity of VEGF were estimated in PICF specimens from peri-implantitis, peri-implant mucositis (PIM) and healthy peri-implant tissues (HI) using machine learning algorithms.

Results: Peri-implantitis exhibited rich neovascular network with expressed density in contact zones toward neutrophil infiltrates without specific pattern variations around TPs, identified in all peri-implantitis specimens (mean particle size 8.9 ± 24.8 µm²; Ti-mass (%) 0.380 ± 0.163). VEGF was significantly more expressed in peri-implantitis (47,065 ± 24.2) compared to periodontitis (31,14 ± 9.15), and positively correlated with its soluble concentrations in PICF (p = 0.01). VEGF was positively correlated to all clinical endpoints and significantly increased in peri-implantitis compared to both PIM and HI, but despite high specificity (96%), its overall diagnostic capacity was average. Two patient clusters were identified in peri-implantitis, one with 8-fold higher VEGF values compared to HI, and second with lower values comparable to PIM.

Significance: VEGF accurately reflects neovascularization in peri-implantitis that was expressed in contact zones toward implant surface without specific histopathological patter variation around TPs. VEGF answered requests for biomarker of peri-implantitis but further research is necessary to decrypt its exact underlying cause.

Keywords: Biomarker; Diagnosis; Machine learning algorithms; Peri-implantitis; Titanium particles; VEGF.

MeSH terms

Biomarkers
Dental Implants*
Humans
Peri-Implantitis* / diagnosis
Titanium
Vascular Endothelial Growth Factor A

Substances

Titanium
Vascular Endothelial Growth Factor A
Dental Implants
Biomarkers