With the introduction of a new interdisciplinary field, osteoimmunology, today, it is well acknowledged that biomaterial-induced inflammation is modulated by immune cells, primarily macrophages, and can be controlled by nanotopographical cues. Recent studies have investigated the effect of surface properties in modulating the immune reaction, and literature data indicate that various surface cues can dictate both the immune response and bone tissue repair. In this context, the purpose of the present study was to investigate the effects of titanium dioxide nanotube (TNT) interspacing on the response of the macrophage-like cell line RAW 264.7. The cells were maintained in contact with the surfaces of flat titanium (Ti) and anodic TNTs with an intertube spacing of 20 nm (TNT20) and 80 nm (TNT80), under standard or pro-inflammatory conditions. The results revealed that nanotube interspacing can influence macrophage response in terms of cell survival and proliferation, cellular morphology and polarization, cytokine/chemokine expression, and foreign body reaction. While the nanostructured topography did not tune the macrophages' differentiation into osteoclasts, this behavior was significantly reduced as compared to flat Ti surface. Overall, this study provides a new insight into how nanotubes' morphological features, particularly intertube spacing, could affect macrophage behavior.

Advanced Institute for Materials Research Sendai 980 8577 Japan

Department of Biochemistry and Molecular Biology Faculty of Biology University of Bucharest 91 95 Splaiul Independentei 050095 Bucharest Romania

Department of Chemistry Faculty of Science King Abdulaziz University P O Box 80203 Jeddah 21569 Saudi Arabia

Department of Materials Science WW4 LKO Friedrich Alexander University 91058 Erlangen Germany

Department of Pediatrics Division of Molecular Pediatrics University Hospital Erlangen 91054 Erlangen Germany

Faculty of Engineering in Foreign Languages University Politehnica of Bucharest 313 Splaiul Indendentei 060042 Bucharest Romania

Regional Centre of Advanced Technologies and Materials 78371 Olomouc Czech Republic

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Lateral Spacing of TiO2 Nanotube Coatings Modulates In Vivo Early New Bone Formation