Zinc-doped ferric oxyhydroxide nano-layer enhances the bactericidal activity and osseointegration of a magnesium alloy through augmenting the formation of neutrophil extracellular traps

Abstract

Implant-associated infections (IAI) and osseointegration disorders are the most common complications in orthopedics. Studies have shown that neutrophils surrounding implants play a vital role in regulating these complications. Although magnesium (Mg) and its alloys are considered promising biodegradable bone implants, their role in neutrophil-mediated antibacteria has not yet been examined. Considering the rapid corrosion of Mg, it is necessary to develop methods to inhibit its corrosion. To solve these issues, a zinc-doped ferric oxyhydroxide nano-layer modified plasma electrolytic oxidation (PEO)-coated Mg alloy (PEO-FeZn) was developed in this study, and its antibacterial, immune anti-infective, and osteogenic ability were systematically evaluated. The results showed that PEO-FeZn nano-layer enhanced the corrosion resistance, biocompatibility, bactericidal activity, and osteoblastic differentiation activity of the Mg alloy. Moreover, PEO-FeZn nano-layer inhibited immune evasion-related gene expression and contributed to the formation of neutrophil extracellular traps (NETs) by activating the extracellular release of DNA fibers and granule proteins, and thereby suppressing bacterial invasion and promoting osseointegration in vivo in Staphylococcus aureus (S. aureus)-infected rat femurs. Overall, the findings of this study could serve as a reference for the fabrication of highly biocompatible and corrosion resistant Mg alloys to address the challenges of IAI and osseointegration disorders. STATEMENT OF SIGNIFICANCE: The widely used metallic biomaterials usually come with the risk of IAI. As the first responder around the biomaterials, neutrophils could form NETs to defense against microorganism and promote tissue remodeling. Therefore, biomaterials addressing antibacterial and neutrophils-modulatory strategies are highly necessary in reducing IAI. To solve these issues, we grew PEO-FeZn nano-layers in situ on Mg alloy using a simple and green technique. The nano-layer not only enhanced the corrosion resistance and biocompatibility of Mg alloy, but also elevated the antibacterial and osteogenesis capability. Moreover, nano-layer contributed to NETs formation, thereby suppressing bacterial invasion and even promoting osseointegration in S.aureus-infected femurs. Accordingly, this functionalized multilayer coating with antibacterial immunity represents a novel therapeutic strategy for IAI and weak osseointegration.

Keywords: Antibacterial immunity; Implant-associated infections; Magnesium alloy; Osseointegration; Zn-doped ferric oxyhydroxide nano-layer.