Gallium-doped thermochemically treated titanium reduces osteoclastogenesis and improves osteodifferentiation

David Piñera-Avellaneda; Judit Buxadera-Palomero; Maria-Pau Ginebra; Elisa Rupérez; José María Manero

doi:10.3389/fbioe.2023.1303313

Gallium-doped thermochemically treated titanium reduces osteoclastogenesis and improves osteodifferentiation

Front Bioeng Biotechnol. 2023 Dec 7:11:1303313. doi: 10.3389/fbioe.2023.1303313. eCollection 2023.

Authors

David Piñera-Avellaneda^{1

2

3}, Judit Buxadera-Palomero^{1

2

3}, Maria-Pau Ginebra^{1

2

3

4}, Elisa Rupérez^{1

2

3}, José María Manero^{1

2

3}

Affiliations

¹ Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Barcelona East School of Engineering (EEBE), Technical University of Catalonia (UPC), Barcelona, Spain.
² Barcelona Research Center in Multiscale Science and Engineering, EEBE, Barcelona, Spain.
³ Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
⁴ Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain.

Abstract

Excessive bone resorption is one of the main causes of bone homeostasis alterations, resulting in an imbalance in the natural remodeling cycle. This imbalance can cause diseases such as osteoporosis, or it can be exacerbated in bone cancer processes. In such cases, there is an increased risk of fractures requiring a prosthesis. In the present study, a titanium implant subjected to gallium (Ga)-doped thermochemical treatment was evaluated as a strategy to reduce bone resorption and improve osteodifferentiation. The suitability of the material to reduce bone resorption was proven by inducing macrophages (RAW 264.7) to differentiate to osteoclasts on Ga-containing surfaces. In addition, the behavior of human mesenchymal stem cells (hMSCs) was studied in terms of cell adhesion, morphology, proliferation, and differentiation. The results proved that the Ga-containing calcium titanate layer is capable of inhibiting osteoclastogenesis, hypothetically by inducing ferroptosis. Furthermore, Ga-containing surfaces promote the differentiation of hMSCs into osteoblasts. Therefore, Ga-containing calcium titanate may be a promising strategy for patients with fractures resulting from an excessive bone resorption disease.

Keywords: bone metastasis; ferroptosis; gallium; osteoclast; osteoporosis; titanium implant.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Ministry of Science and Innovation of Spain through the RTI 2018-098075-B-C21 project, cofounded by the EU through the European Regional Development Funds (MINECO-FEDER, EU). The authors also thank the Spanish Government for financial support through PID 2021-125150OB-I00 project, as well as the FPI-MEC scholarship of DP-A.