一种双功能钛镓合金：通过干扰铁代谢抑制生物膜形成和破骨细胞生成分化。
A dual functional Ti-Ga alloy: inhibiting biofilm formation and osteoclastogenesis differentiation via disturbing iron metabolism.
作者信息
Li Fupeng, Huang Kai, Wang Jinbing, Yuan Kai, Yang Yiqi, Liu Yihao, Zhou Xianhao, Kong Keyu, Yang Tao, He Jian, Liu Chunjie, Ao Haiyong, Liu Fengxiang, Liu Qian, Tang Tingting, Yang Shengbing
机构信息
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.
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.
出版信息
Biomater Res. 2023 Mar 29;27(1):24. doi: 10.1186/s40824-023-00362-1.
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 Ga 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 Ga 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 Ga ions to inhibit biofilm formation and osteoclast differentiation.
背景
尽管生物医学植入物已广泛应用于骨科治疗，但仍有两个主要临床挑战有待解决，一是细菌感染导致生物膜形成，二是植入过程中因破骨细胞过度活化而出现无菌性松动。这些因素会引发诸多临床问题，甚至导致植入失败。因此，有必要赋予植入物抗生物膜和预防无菌性松动的特性，以促进植入物与骨组织的融合，实现成功植入。为实现这一目标，本研究旨在通过使用镓（Ga）作为成分来开发一种具有抗生物膜和抗无菌性松动双重功能的生物相容性钛合金。
方法
制备了一系列Ti-Ga合金。我们检测了Ga含量、Ga分布、硬度、拉伸强度、生物相容性以及体内外抗生物膜性能。我们还探究了Ga离子如何抑制金黄色葡萄球菌（S. aureus）和大肠杆菌（E. coli）的生物膜形成以及破骨细胞分化。
结果
该合金在体外对金黄色葡萄球菌和大肠杆菌均表现出出色的抗生物膜特性，在体内对金黄色葡萄球菌也具有良好的抗生物膜性能。蛋白质组学结果表明，Ga离子可干扰金黄色葡萄球菌和大肠杆菌的细菌铁代谢，抑制细菌生物膜形成。此外，Ti-Ga合金可通过靶向铁代谢抑制核因子κB受体活化因子配体（RANKL）依赖性破骨细胞分化和功能，进而抑制NF-κB信号通路的激活，因此显示出其预防无菌性松动的潜力。
结论
本研究提供了一种先进的Ti-Ga合金，可作为一种有前景的骨科植入物原材料用于各种临床场景。这项工作还揭示了铁代谢是Ga离子抑制生物膜形成和破骨细胞分化的共同靶点。
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