A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio-genesis towards ameliorative osseointegration
Open accessAbstract
A multifaceted coating for hard tissue implants, with favorable osteogenesis, angiogenesis, and osteoimmunomodulation abilities, would be of great value since it could improve osseointegration and alleviate prosthesis loosening. However, to date there are few coatings that fully satisfy these criteria. Herein we describe a microporous TiO 2 coating decorated with hydroxyapatite (HA) nanoparticles that is generated by micro-arc oxidation of pure titanium (Ti) and followed annealing. By altering the annealing temperature, it is possible to simultaneously tune the coating's physical (morphology and wettability) and chemical (composites and crystallinity) properties. A coating produced with micro-arc oxidization (MAO) with an annealing temperature of 650 °C (MAO-650) exhibits numerous favorable physicochemical properties, such as hybrid micro-nano morphology, superhydrophilicity, and highly crystalline HA nanoparticles. In vitro experiments reveal that the MAO-650 coating not only supports proliferation and differentiation of both osteoblasts and endothelial cells, but also inhibits the inflammatory response of macrophages and enables a favorable osteoimmunomodulation to facilitate osteo/angio-genesis. In vivo evaluation mirrors these results, and shows that the MAO-650 coating results in ameliorative osseointegration when compared with the pristine MAO coating. These data highlight the profound effect of surface physicochemical properties on the regulation of osteo/angio-genesis and osteoimmunomodulation in the enhancement of osseointegration.
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Interaction between ECM on the surface of endothelial cells and integrins can initiate the intracellular PI3K-AKT-eNOS signaling pathway, leading to the production of NO.
“It is well-documented that the interaction between the ECM on the surface of endothelial cells and integrins can initiate the intracellular PI3K-AKT-eNOS signaling pathway, leading to the production of NO.”
From Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models (2025) · cites this paper as [47]
Section 3.5 states that eNOS synthesizes NO in endothelial cells, supporting the final part of the claim. It describes VEGFR–PLC–IP3–calcium signaling and BMP2 receptor signaling, but does not support the attributed ECM–integrin initiation of a PI3K–AKT–eNOS pathway. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThis enhancement is likely due to the activation of eNOS following the inoculation of endothelial cells onto the scaffold and their subsequent contact with the ECM, initiating a series of reactions that result in increased NO secretion.
“This enhancement is likely due to the activation of eNOS following the inoculation of endothelial cells onto the scaffold and their subsequent contact with the ECM, initiating a series of reactions that result in increased NO secretion [47,48].”
From Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models (2025) · cites this paper as [47]
The discussion (p. 16/46) says VEGF activates eNOS, which produces NO, and the methods (p. 8/46) describe inoculating endothelial cells onto specimen surfaces. The paper does not say that subsequent contact with the ECM triggers eNOS activation, nor does it report increased NO secretion from that contact; it describes VEGF signaling as the route to eNOS activation. (LLM, conf=0.85)
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- Authors
- Bai, L., Du, Z., Du, J., Yao, W., Zhang, J., Weng, Z., Liu, S., Zhao, Y., Liu, Y., Zhang, X., Huang, X., Yao, X., Crawford, R., Hang, R., Huang, D., Tang, B., & Xiao, Y.
- Affiliations
- Queensland University of Technology (AU)
- Taiyuan University of Technology (CN)
- Shanxi Medical University (CN)
- Corresponding author
- Huang, Xiaobo
- Hang, Ruiqiang
- Huang, Di
- Xiao, Yin
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 162
- Pages
- 154-169
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2790044190
- Semantic Scholar
- 12df7ea7aecb42eda735391d73c614df26127aad
- Cited by
- 265
- References
- 84
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 30 · 2023: 33 · 2022: 51 · 2021: 54 · 2020: 34 · 2019: 25 · 2018: 9
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- green
- eprints.qut.edu.au
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by-nc-nd)
- Griffith Research Online (submittedVersion, other-oa)
- Funders
- National Natural Science Foundation of China (31400815, 11502158, 31771025, 51671140, 11632013, 31700834)
- Prince Charles Hospital Research Foundation
- Australia-China Centre for Tissue Engineering and Regenerative Medicine at QUT
- China Scholarship Council (201606930017)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Engineering › Mechanical Engineering › Surface Treatment and Coatings
- Physical Sciences › Materials Science › Materials Chemistry › Titanium Alloys Microstructure and Properties
- Keywords
- titanium implants, osseointegration, plasma electrolytic oxidation, TiO2 coating, hydroxyapatite nanoparticles, annealing temperature, osteoimmunomodulation, bone formation, angiogenesis, superhydrophilicity, macrophage inflammation, osteogenic differentiation, endothelial cell proliferation, implant loosening, hard tissue implants
- MeSH terms
- RAW 264.7 Cells, Animals, Cell Line, Cells, Cultured, Humans, Macrophages, Osteoblasts, Surface Properties, Titanium, Osseointegration, Durapatite, Neovascularization, Physiologic, Coated Materials, Biocompatible, Endothelial Cells, Mice
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