journal article·2026-02-25Open access

Influence of Micro-Nanostructured Anatase-Coated SLA Titanium on Macrophage Behavior

Leila Mohammadnejad, Madeline Mangold, Hannah Conrady, Wafa Zafira, Evi Kimmerle-Mueller, Peter Schneider, Barbara Illing, Christiane von Ohle, Annika Hechler, Frank Rupp, Stefanie Krajewski

Abstract

The success of titanium dental implants rely on osseointegration, influenced by surface properties and early immune responses. While sandblasted and acid-etched (SLA) titanium surfaces have shown clinical success, macrophage-mediated immune responses at these interfaces remain poorly understood. Anatase nanostructures have been shown to influence macrophage polarization on smooth titanium, but their effects on micro-rough SLA surfaces are not fully explored. This study investigates the immunomodulatory effects of micro-nanostructured anatase coatings on SLA titanium using human monocyte-derived macrophages (MDMs). M0-MDMs, were cultured and polarized to M1 and M2- macrophages on Ti-machined, Ti-SLA, Ti-SLA-anatase, and coverslip control surfaces for 48 h. Macrophage behavior was assessed using CCK-8 assay, confocal microscopy, SEM, ELISA, and qRT-PCR. All surfaces demonstrated excellent cytocompatibility, with similar macrophage viability across all investigated groups. M1 macrophages showed upregulation of CCR7 and TNF-α, while M2 macrophages expressed CD209 and CCL13 across all surfaces. Importantly, Ti-SLA-anatase did not significantly alter M1 or M2 markers, cytokine secretion, or gene expression, and did not exacerbate inflammatory responses. Micro-nanostructured anatase coatings on SLA titanium are immunologically well-tolerated and do not increase inflammation. These findings, combined with previously reported enhanced osteogenic properties, suggest the clinical potential of anatase-coated SLA surfaces.
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Research context

OpenAlex topics: Bone Tissue Engineering Materials · Dental Implant Techniques and Outcomes · Periodontal Regeneration and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Medical Materials Science & Technology, Institute of Biomedical Engineering, University Hospital Tübingen, Osianderstr. 2-8, 72076 Tübingen, Germany

Department of Conservative Dentistry and Periodontology, University Hospital Tübingen, Osianderstr. 2-8, 72076 Tübingen, Germany

Funding

Medentis Medical, Bad-Neuenahr-Ahrweiler, Germany · Open Access Publishing Fund of the University of Tübingen

References (35)

Show source-provided references
1. Wu, H., Chen, X., Kong, L., and Liu, P. (2023). Mechanical and biological properties of titanium and its alloys for oral implant with preparation techniques: A review. Materials, 16.10.3390/ma16216860 ↗
2. Advances in implant surface modifications to improve osseointegration10.1039/D1MA00675D ↗
3. Surface characteristics of dental implants: A review10.1016/j.dental.2017.09.007 ↗
4. Velasco-Ortega, E., Ortiz-Garcia, I., Jiménez-Guerra, A., Núñez-Márquez, E., Moreno-Muñoz, J., Rondón-Romero, J.L., Cabanillas-Balsera, D., Gil, J., Muñoz-Guzón, F., and Monsalve-Guil, L. (2021). Osseointegration of sandblasted and acid-etched implant surfaces. A histological and histomorphometric study in the rabbit. Int. J. Mol. Sci., 22.10.3390/ijms22168507 ↗
5. Xu, J., Zhang, J., Shi, Y., Tang, J., Huang, D., Yan, M., and Dargusch, M.S. (2022). Surface modification of biomedical Ti and Ti alloys: A review on current advances. Materials, 15.10.3390/ma15051749 ↗
6. Vieira, G.M., Almeida, T.C., Oliveira, F.P., Azzi, P.C., Rodrigues, C.F., Souza, R.L., Lacerda, S.M.S., Lages, F.S., and Martins, M.D. (2025). Comparative Study of Acid Etching and SLA Surface Modification for Titanium Implants. Materials, 18.10.3390/ma18071632 ↗
7. Tuikampee, S., Chaijareenont, P., Rungsiyakull, P., and Yavirach, A. (2024). Titanium surface modification techniques to enhance osteoblasts and bone formation for dental implants: A narrative review on current advances. Metals, 14.10.3390/met14050515 ↗
8. Reality of dental implant surface modification: A short literature review10.2174/1874120701408010114 ↗
9. Enhancing surface free energy and hydrophilicity through chemical modification of microstructured titanium implant surfaces
10. Macrophages in the process of osseointegration around the implant and their regulatory strategies10.1080/03008207.2023.2300455 ↗
11. Pitchai, M.S., Ipe, D.S., and Hamlet, S. (2023). The effect of titanium surface topography on adherent macrophage integrin and cytokine expression. J. Funct. Biomater., 14.10.3390/jfb14040211 ↗
12. Biomimetic surface topography as a potential modulator of macrophages inflammatory response to biomaterials10.1016/j.bioadv.2022.213128 ↗
13. Titanium surface characteristics, including topography and wettability, alter macrophage activation10.1016/j.actbio.2015.12.003 ↗
14. Biomaterial based modulation of macrophage polarization: A review and suggested design principles10.1016/j.mattod.2015.01.019 ↗
15. Micro-and nanopatterned topographical cues for regulating macrophage cell shape and phenotype10.1021/acsami.5b10589 ↗
16. Cao, X., Luo, B., Mu, Y., Wang, C., Lu, R., Yao, Y., and Chen, S. (2024). The regulatory effect of TiO(2) nanotubes loaded with graphene oxide on macrophage polarization in an inflammatory environment. BMC Oral Health, 24.10.1186/s12903-024-04608-9 ↗
17. Enhancing Bone-Titanium integration through hydrogel coating mediated sequential M1/M2 polarization of interfacial macrophages10.1016/j.cej.2024.157088 ↗
18. Promoting osseointegration of titanium by pH-responsive releasing of H2S and optimizing polarization time for macrophages10.1016/j.compositesb.2023.110554 ↗
19. Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration10.1126/sciadv.abf6654 ↗
20. TiO2 nanostructured implant surface-mediated M2c polarization of inflammatory monocyte requiring intact cytoskeleton rearrangement10.1186/s12951-022-01751-9 ↗
21. Nanotubular TiO2 regulates macrophage M2 polarization and increases macrophage secretion of VEGF to accelerate endothelialization via the ERK1/2 and PI3K/AKT pathways10.2147/IJN.S188439 ↗
22. Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways
23. Titanium dioxide nanotubes promote M2 polarization by inhibiting macrophage glycolysis and ultimately accelerate endothelialization10.1002/iid3.429 ↗
24. Mohammadnejad, L., Zafira, W., Schultheiss, J., Crocoll, L., Kimmerle-Mueller, E., Illing, B., Keppeler, K., Turad, M., Hechler, A., and Ohle, C.v. (2026). Superhydrophilic Hierarchical anatase Coating on Sandblasted, Acid-Etched Titanium: In Vitro apatite Formation and Osteoblast Responses and the Role of Polar Surface Free Energy. J. Funct. Biomater., 17.10.3390/jfb17020080 ↗
25. Mohammadnejad, L., Theurer, A., Alber, J., Illing, B., Kimmerle-Mueller, E., Schultheiss, J., Krajewski, S., and Rupp, F. (2024). Surface-mediated modulation of different biological responses on anatase-coated titanium. J. Funct. Biomater., 15.10.3390/jfb15020029 ↗
26. Characterization of in vitro generated human polarized macrophages10.4172/2155-9899.1000380 ↗
27. Polarization and Characterization of M1 and M2 Human Monocyte-Derived Macrophages on Implant Surfaces
28. Lugo-Villarino, G., Troegeler, A., Balboa, L., Lastrucci, C., Duval, C., Mercier, I., Bénard, A., Capilla, F., Al Saati, T., and Poincloux, R. (2018). The C-type lectin receptor DC-SIGN has an anti-inflammatory role in human M (IL-4) macrophages in response to Mycobacterium tuberculosis. Front. Immunol., 9.10.3389/fimmu.2018.01123 ↗
29. Atri, C., Guerfali, F.Z., and Laouini, D. (2018). Role of human macrophage polarization in inflammation during infectious diseases. Int. J. Mol. Sci., 19.10.3390/ijms19061801 ↗
30. CD163 and CCR7 as markers for macrophage polarisation in lung cancer microenvironment
31. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method10.1006/meth.2001.1262 ↗
32. Modulation of macrophage phenotype by cell shape10.1073/pnas.1308887110 ↗
33. Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors10.1016/j.celrep.2021.109955 ↗
34. Hickman, E., Smyth, T., Cobos-Uribe, C., Immormino, R., Rebuli, M.E., Moran, T., Alexis, N.E., and Jaspers, I. (2023). Expanded characterization of in vitro polarized M0, M1, and M2 human monocyte-derived macrophages: Bioenergetic and secreted mediator profiles. PLoS ONE, 18.10.1371/journal.pone.0279037 ↗
35. Nanostructured titanium regulates osseointegration via influencing macrophage polarization in the osteogenic environment10.2147/IJN.S163956 ↗