High-strength biodegradable zinc alloy implants with antibacterial and osteogenic properties for the treatment of MRSA-induced rat osteomyelitis

Bo Jia; Zechuan Zhang; Yifu Zhuang; Hongtao Yang; Yu Han; Qiang Wu; Xiufeng Jia; Yanhui Yin; Xinhua Qu; Yufeng Zheng; Kerong Dai

doi:10.1016/j.biomaterials.2022.121663

High-strength biodegradable zinc alloy implants with antibacterial and osteogenic properties for the treatment of MRSA-induced rat osteomyelitis

Biomaterials. 2022 Aug:287:121663. doi: 10.1016/j.biomaterials.2022.121663. Epub 2022 Jul 5.

Authors

Bo Jia¹, Zechuan Zhang², Yifu Zhuang³, Hongtao Yang⁴, Yu Han⁵, Qiang Wu⁵, Xiufeng Jia⁶, Yanhui Yin⁷, Xinhua Qu⁸, Yufeng Zheng⁹, Kerong Dai¹⁰

Affiliations

¹ 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.
² School of Materials Science and Engineering, Peking University, Beijing, 100871, China.
³ Trauma Center, Department of Orthopaedics and Traumatology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 201620, China.
⁴ School of Engineering Medicine, Beihang University, Beijing, 100191, China.
⁵ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200011, China.
⁶ Department of Orthopaedic Surgery, Wudi People's Hospital, Binzhou, 251900, China.
⁷ School of Economics and Trade, Shandong Management University, Jinan, 250357, China.
⁸ Department of Bone and Joint Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
⁹ School of Materials Science and Engineering, Peking University, Beijing, 100871, China. Electronic address: yfzheng@pku.edu.cn.
¹⁰ Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200011, China. Electronic address: krdai@163.com.

PMID: 35810539
DOI: 10.1016/j.biomaterials.2022.121663

Abstract

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.

Keywords: Antibacterial; Biodegradable metals; Implant-related infections; Osteogenesis; Zn-Li-Ag alloy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Absorbable Implants
Alloys / pharmacology
Animals
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Biocompatible Materials / pharmacology
Corrosion
Materials Testing
Methicillin-Resistant Staphylococcus aureus*
Osteomyelitis* / drug therapy
Rats
X-Ray Microtomography
Zinc / pharmacology

Substances

Alloys
Zinc
Anti-Bacterial Agents
Biocompatible Materials