Jia Bo, Zhang Zechuan, Zhuang Yifu, Yang Hongtao, Han Yu, Wu Qiang, Jia Xiufeng, Yin Yanhui, Qu Xinhua, Zheng Yufeng, Dai Kerong
Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200011, China; Department of Bone and Joint Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
School of Materials Science and Engineering, Peking University, Beijing, 100871, China.
Biomaterials. 2022 Aug;287:121663. doi: 10.1016/j.biomaterials.2022.121663. Epub 2022 Jul 5.
Implant-related infections caused by drug-resistant bacteria remain a major challenge faced by orthopedic surgeons. Furthermore, ideal prevention and treatment methods are lacking in clinical practice. Here, based on the antibacterial and osteogenic properties of Zn alloys, Ag and Li were selected as alloying elements to prepare biodegradable Zn-Li-Ag ternary alloys. Li and Ag addition improved the mechanical properties of Zn-Li-Ag alloys. The Zn-0.8Li-0.5Ag alloy exhibited the highest ultimate tensile strength (>530 MPa). Zn-Li-Ag alloys showed strong bactericidal effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. RNA sequencing revealed two MRSA-killing mechanisms exhibited by the Zn-0.8Li-0.5Ag alloy: cellular metabolism disturbance and induction of reactive oxygen species production. To verify that the therapeutic potential of the Zn-0.8Li-0.5Ag alloy is greater than that of Ti intramedullary nails, X-ray, micro-computed tomography, microbiological, and histological analyses were conducted in a rat femoral model of MRSA-induced osteomyelitis. Treatment with Zn-0.8Li-0.5Ag alloy implants resulted in remarkable infection control and favorable bone retention. The in vivo safety of this ternary alloy was confirmed by evaluating vital organ functions and pathological morphologies. We suggest that, with its good antibacterial and osteogenic properties, Zn-0.8Li-0.5Ag alloy can serve as an orthopedic implant material to prevent and treat orthopedic implant-related infections.
由耐药菌引起的植入物相关感染仍然是骨科医生面临的一项重大挑战。此外，临床实践中缺乏理想的预防和治疗方法。在此，基于锌合金的抗菌和成骨特性，选择银和锂作为合金元素来制备可生物降解的锌-锂-银三元合金。添加锂和银改善了锌-锂-银合金的机械性能。锌-0.8锂-0.5银合金表现出最高的极限抗拉强度（>530兆帕）。锌-锂-银合金在体外对耐甲氧西林金黄色葡萄球菌（MRSA）显示出强大的杀菌作用。RNA测序揭示了锌-0.8锂-0.5银合金展现出的两种杀死MRSA的机制：细胞代谢紊乱和诱导活性氧产生。为了验证锌-0.8锂-0.5银合金的治疗潜力大于钛髓内钉，在MRSA诱导的骨髓炎大鼠股骨模型中进行了X射线、微计算机断层扫描、微生物学和组织学分析。用锌-0.8锂-0.5银合金植入物进行治疗导致感染得到显著控制且骨保留良好。通过评估重要器官功能和病理形态证实了这种三元合金的体内安全性。我们认为，锌-0.8锂-0.5银合金具有良好的抗菌和成骨特性，可作为一种骨科植入材料用于预防和治疗骨科植入物相关感染。
