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ORIGINAL RESEARCH ARTICLE

Titanium particles modulate macrophage macropinocytosis, cytokine secretion, and polarization-associated gene expression via NF-κB-dependent mechanisms

Justin P. Galliani1 ,  Jennifer W. Bradford2 ,  Dalton Ard2 ,  Michael A. Washington2,3 ,  Sanjiv Kumar3 ,  Kenneth M. Hussey1 ,  Adam R. Lincicum1 ,  Kimberly Ann Inouye1 ,  Steven E. Handel4 ,  Brendan Marshall5 ,  Thomas M. Johnson1*
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1 Department of Periodontics, Army Postgraduate Dental School, Postgraduate Dental College, Uniformed Services University, Fort Gordon, Georgia, United States of America
2 Department of Biological Sciences, College of Science and Mathematics, Augusta University, Augusta, Georgia, United States of America
3 Department of Clinical Investigation, Dwight David Eisenhower Army Medical Center, Fort Gordon, Georgia, United States of America
4 Department of Prosthodontics, Army Postgraduate Dental School, Postgraduate Dental College, Uniformed Services University, Fort Gordon, Georgia, United States of America
5 Electron Microscopy and Histology Core, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, United States of America
Global Translational Medicine, 026030002 https://doi.org/10.36922/GTM026030002
Received: 15 January 2026 | Revised: 25 April 2026 | Accepted: 29 April 2026 | Published online: 9 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The pathogenesis of peri-implantitis reflects complex interactions among host cells, a distinct oral biofilm, and metal particles, with many aspects still unresolved. The purpose of this investigation is to examine the role of nuclear factor-kappa B (NF-κB) signaling in macrophage responses to titanium oxide (TiO2) particles. LysMCre and p65-knockout bone marrow-derived macrophages (BMDMs) were exposed to TiO2 particles for one or five days. Media were collected at each time point, and the concentrations of various cytokines were recorded. Expression of macrophage polarity markers was assessed via quantitative polymerase chain reaction. Scanning electron microscopy and transmission electron microscopy were used to evaluate cellular morphological changes and the internalization of TiO2 particles. Macrophage inflammatory protein (MIP)-1β concentration significantly increased in all TiO2-exposed groups compared with unexposed controls, and MIP-1α concentrations followed a similar pattern. TiO2 particles induced distinct polarity marker expression profiles in LysMCre versus p65-knockout BMDMs, the latter showing elevated normalized expression of M2 polarity markers. Compared with LysMCre cultures, p65-knockout BMDMs showed less internalization of TiO2 and only rare signs of macropinocytosis. These findings suggest that macrophage responses to TiO2 particles are influenced by NF-κB signaling at multiple levels, including particle internalization, chemokine secretion, and polarization-associated gene expression.

Keywords
Macrophages
Inflammation
Nuclear factor-kappa B
Titanium
Dental implants
Peri-implantitis
Funding
Funding for animal housing was provided by the Office of the Executive Vice President for Research at Augusta University.
Conflict of interest
The authors declare no commercial or financial relationships that could be construed as a potential conflict of interest.
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Global Translational Medicine, Electronic ISSN: 2811-0021 Print ISSN: 3060-8600, Published by AccScience Publishing
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