Degradation of differently processed Mg-based implants leads to distinct foreign body reactions (FBRs) through dissimilar signaling pathways

Abstract

Mg alloys have mechanical properties compatible with human bones. However, their rapid degradation and associated foreign body reactions in vivo significantly limit their application for human implants. In this study, three differently processed Mg alloys, pure Mg (PM), cold extruded Mg alloy AZ31 (CE AZ31), and fully annealed AZ31 Mg alloy (FA AZ31) were comparatively investigated for their potential as implants using a rat model. All three implanted Mg alloys do not show any impact on hepato- and renal function, nor any signs of observable changes to vital organs. Proteomics analysis of tissues directly contacting the implants 2.5 months post implantation revealed that FA AZ31 activates very few inflammation and immune associated signaling pathways; while the CE AZ31 and PM produce more significant inflammatory responses as confirmed by cytokine array analyses. Further, FA AZ31 activated pathways for cell organization and development that may improve the recovery of injured tissues. Structurally, EBSD analysis reveals that the FA AZ31 alloy has a higher ratio of first-order pyramidal orientated (10–11){10–1–2} grain texture with a value of 0.25, while PM and CE AZ31 alloys have lower ratios of first-order pyramidal orientated texture with the values of 0.16 and 0.17, respectively. This is associated with recovery and recrystallisation during annealing which promotes grain texture which exhibits enhanced degradation behaviours and induces a more limited immune response in vivo. In conclusion, the FA AZ31 demonstrated better biocompatibility and corrosion resistance and is a promising candidate for metal-based degradable implants which warrants further investigation.