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Sr/Zn-doped TiO2 coating enhances implant osseointegration by directing macrophage M2 polarization mediated osteoimmunomodulation.

Created on 01 Aug 2026

Authors

Nuo-Ya Yang, Xiao-Lu Li, Tian-Xia Zheng, Yuan-Yuan Ding, Jiu-Peng Deng, Wei Dong, Hui Chen, Meng-Chun Qi, Li-Fang Feng, Jun-Yuan Zhang

Published in

Colloids and surfaces. B, Biointerfaces. Volume 268. Issue Pt 1. Pages 116026. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

Bioinert titanium implants lack immunomodulatory capacity to direct favorable osteoimmune responses during osseointegration. While Sr/Zn-doped TiO₂ micro-arc oxidation coatings have been shown to enhance bone regeneration through multicellular crosstalk, the direct immunoregulatory mechanism remain unclear. Here we demonstrate that Sr/Zn coating actively induces macrophage M2 polarization through modulation of key inflammatory pathways, establishing a pro-regenerative osteoimmune microenvironment. In vitro, the coating facilitated RAW264.7 macrophage transition from M1 to M2 phenotype, confirmed by immunofluorescence staining, RT-qPCR and Flow Cytometry. Transcriptomic profiling with KEGG enrichment revealed significant modulation of IL-17, NF-κB, TNF, Toll-like receptor, chemokine, and Wnt signaling pathways. Macrophage-conditioned medium from Sr/Zn-coated surfaces significantly enhanced osteoblast differentiation and angiogenic factor expression. In vivo, Sr/Zn-coated implants reduced M1 marker iNOS while elevating M2 marker Arg-1, accompanied by enhanced BMP2, Runx2, CD31 and VEGF expression. Micro-CT and histological analyses confirmed superior osseointegration with increased bone volume fraction and bone-implant contact. This study provides the first direct evidence that Sr/Zn-doped TiO₂ coatings enhance osseointegration through macrophage M2 polarization-directed osteoimmunomodulation, advancing our understanding of bioactive coating design for orthopedic and dental applications.

PMID:
42537309
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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