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

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

PMC · DOI: 10.3390/jfb17030111 · Journal of Functional Biomaterials · 2026-02-25

## TL;DR

This study shows that anatase-coated titanium surfaces used in dental implants do not trigger harmful immune responses and are well-tolerated by macrophages.

## Contribution

The study is the first to investigate the immunomodulatory effects of anatase coatings on micro-rough SLA titanium surfaces.

## Key findings

- Anatase-coated SLA titanium surfaces showed no significant changes in macrophage polarization or cytokine secretion.
- All surfaces demonstrated excellent cytocompatibility with similar macrophage viability.
- The coatings did not exacerbate inflammatory responses, suggesting clinical potential for dental implants.

## 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.

## Linked entities

- **Genes:** CCR7 (C-C motif chemokine receptor 7) [NCBI Gene 1236], TNF (tumor necrosis factor) [NCBI Gene 7124], CD209 (CD209 molecule) [NCBI Gene 30835], CCL13 (C-C motif chemokine ligand 13) [NCBI Gene 6357]

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, SLA (Src like adaptor) [NCBI Gene 6503] {aka SLA1, SLAP}, CCL13 (C-C motif chemokine ligand 13) [NCBI Gene 6357] {aka CKb10, MCP-4, NCC-1, NCC1, SCYA13, SCYL1}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, CCR7 (C-C motif chemokine receptor 7) [NCBI Gene 1236] {aka BLR2, CC-CKR-7, CCR-7, CD197, CDw197, CMKBR7}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, CD209 (CD209 molecule) [NCBI Gene 30835] {aka CDSIGN, CLEC4L, DC-SIGN, DC-SIGN1, hDC-SIGN}
- **Diseases:** fibrosis (MESH:D005355), injury to (MESH:D014947), inflammation (MESH:D007249), cytotoxic (MESH:D064420)
- **Chemicals:** ethanol (MESH:D000431), Triton X-100 (MESH:D017830), penicillin (MESH:D010406), PI (MESH:D010716), PBS (MESH:D007854), streptomycin (MESH:D013307), H2S (MESH:D006862), Pd (MESH:D010165), reactive oxygen species (MESH:D017382), C-28051 (-), water (MESH:D014867), trypan blue (MESH:D014343), Alexa Fluor 488 (MESH:C000711379), Au (MESH:D006046), paraformaldehyde (MESH:C003043), dT (MESH:D013936), glutaraldehyde (MESH:D005976), Tween 20 (MESH:D011136), CCK-8 (MESH:D012844), CO2 (MESH:D002245), Ti (MESH:D014025), LPS (MESH:D008070), Anatase (MESH:C009495), Graphene-oxide (MESH:C000628730)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** M3010X, M3003E
- **Cell lines:** THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13026796/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC13026796/full.md

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Source: https://tomesphere.com/paper/PMC13026796