A dual functional Ti-Ga alloy: inhibiting biofilm formation and osteoclastogenesis differentiation via disturbing iron metabolism

Fupeng Li; Kai Huang; Jinbing Wang; Kai Yuan; Yiqi Yang; Yihao Liu; Xianhao Zhou; Keyu Kong; Tao Yang; Jian He; Chunjie Liu; Haiyong Ao; Fengxiang Liu; Qian Liu; Tingting Tang; Shengbing Yang

doi:10.1186/s40824-023-00362-1

A dual functional Ti-Ga alloy: inhibiting biofilm formation and osteoclastogenesis differentiation via disturbing iron metabolism

Biomater Res. 2023 Mar 29;27(1):24. doi: 10.1186/s40824-023-00362-1.

Authors

Fupeng Li^#¹, Kai Huang^#², Jinbing Wang^#³, Kai Yuan¹, Yiqi Yang¹, Yihao Liu¹, Xianhao Zhou¹, Keyu Kong¹, Tao Yang⁴, Jian He⁵, Chunjie Liu⁵, Haiyong Ao⁶, Fengxiang Liu⁷, Qian Liu⁸, Tingting Tang⁹, Shengbing Yang¹⁰

Affiliations

¹ Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
² Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. kai_huang@aliyun.com.
³ Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
⁴ Department of Materials Science and Engineering, Hong Kong Institute for Advanced Study, College of Science and Engineering, City University of Hong Kong, Hong Kong, China.
⁵ M-Duke Medical Technology (Shanghai) Co., Ltd, Shanghai, Shanghai, China.
⁶ Jiangxi Key Laboratory of Nanobiomaterials & School of Materials Science and Engineering, East China Jiaotong University, Nanchang, 330000, China.
⁷ Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. liu_fengxiang@126.com.
⁸ Department of laboratory medicine, Ren Ji Hospital, Shanghai Jiao tong university school of medicine, Shanghai, 200127, China. liuqian_rj@shsmu.edu.cn.
⁹ Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. ttt@sjtu.edu.cn.
¹⁰ Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. shengbingyang@shsmu.edu.cn.

^# Contributed equally.

Abstract

Background: Although biomedical implants have been widely used in orthopedic treatments, two major clinical challenges remain to be solved, one is the bacterial infection resulting in biofilm formation, and the other is aseptic loosening during implantation due to over-activated osteoclastogenesis. These factors can cause many clinical issues and even lead to implant failure. Thus, it is necessary to endow implants with antibiofilm and aseptic loosening-prevention properties, to facilitate the integration between implants and bone tissues for successful implantation. To achieve this goal, this study aimed to develop a biocompatible titanium alloy with antibiofilm and anti-aseptic loosening dual function by utilizing gallium (Ga) as a component.

Methods: A series of Ti-Ga alloys were prepared. We examined the Ga content, Ga distribution, hardness, tensile strength, biocompatibility, and anti-biofilm performance in vitro and in vivo. We also explored how Ga³⁺ ions inhibited the biofilm formation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and osteoclast differentiation.

Results: The alloy exhibited outstanding antibiofilm properties against both S. aureus and E. coli in vitro and decent antibiofilm performance against S. aureus in vivo. The proteomics results demonstrated that Ga³⁺ ions could disturb the bacterial Fe metabolism of both S. aureus and E. coli, inhibiting bacterial biofilm formation. In addition, Ti-Ga alloys could inhibit receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and function by targeting iron metabolism, then suppressing the activation of the NF-κB signaling pathway, thus, showing their potential to prevent aseptic loosening.

Conclusion: This study provides an advanced Ti-Ga alloy that can be used as a promising orthopedic implant raw material for various clinical scenarios. This work also revealed that iron metabolism is the common target of Ga³⁺ ions to inhibit biofilm formation and osteoclast differentiation.

Keywords: Anti-biofilm; Bacterial adhesion; Implant-associated infections; Ti-Ga alloy.

Abstract

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