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Differential Neutrophil Responses to Smooth Titanium: A Double-Edged Sword for the Abutment-Gingival Interface (An In
Tian Xu1,2, Tulio Fernandez-Medina1,2
1School of Dentistry - The University of Queensland, Brisbane, Australia.
Introduction:
The role of immunity in the failure of implantable devices has been historically overlooked in implant dentistry. This study investigates how neutrophils and blood plasma proteins interacting with titanium (Ti) surfaces influence the early inflammatory response.
Methods:
Three distinct Ti surfaces (Ti-320, Ti-1200, and Ti-4000) with varying roughness were prepared by serial grinding. For subsequent functional assays, human neutrophils and plasma were isolated from healthy donor blood and characterized for phenotype confirmation. We then analyzed surface roughness, protein corona deposition, and the Ti-protein interface. Neutrophil responses were assessed by quantifying the release of cytokines and enzymatic proteins, in addition to the extent of NETosis area and nuclear circularity.
Results:
The average roughness was 11.94 ± 1.99 nm (Ti-320), 7.52 ± 1.21 nm (Ti-1200), and 2.63 ± 0.49 nm (Ti-4000). The isolated neutrophils exhibited high recovery (7.05 × 106 ± 3.45 × 106 cells/mL), viability (91.1 ± 2.3%), and purity (97.27 ± 2.06%). Protein deposition on all surfaces comprised medium molecular weight, low molecular weight (LMW), and high molecular weight (HMW) proteins. Fourier transform infrared (FTIR) spectroscopy revealed a difference in protein structure between the surfaces, although this finding was not statistically significant. Functionally, Ti-4000 surfaces exhibited significantly higher levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and CXCL-10), elastase, and myeloperoxidase (MPO). Conversely, Ti-320 surfaces promoted higher levels of the anti-inflammatory cytokines IL-4 and IL-10.
Conclusions:
This in vitro study demonstrates that Ti surface properties are associated with distinct protein corona compositions that promote a proinflammatory response on Ti-4000 surfaces and a more favorable, anti-inflammatory profile on Ti-320 surfaces (reduced elastase and NETosis). These findings suggest surface modifications can guide neutrophil responses toward a less proinflammatory state, though further in vivo research is needed to confirm these results.
