Improved biocompatibility of Zn–Ag-based stent materials by microstructure refinement

The metallurgical engineering of bioresorbable zinc (Zn)-based medical alloys would greatly benefit from clarification of the relationships between material properties and biological responses. Here we investigate the biocompatibility of three Zn-based silver (Ag)-containing alloys, ranging from binary to quinary alloy systems. Selected binary and quinary Zn–Ag-based alloys underwent solution treatment (ST) to increase the solubility of Ag-rich phases within the Zn bulk matrix, yielding two different microstructures (one without ST and a different one with ST) with the same elemental composition. This experimental design was intended to clarify the relationship between elemental profile/microstructure and biocompatibility for the Zn–Ag system. We found that the quinary alloy system (Zn–4Ag–0.8Cu–0.6Mn–0.15Zr) performed significantly better, in terms of histomorphometry, than any alloy system we have evaluated to date. Furthermore, when solution treated to increase strength and ductility and reduce the fraction of Ag-rich phases, the quinary alloy's biocompatibility further improved. In vitro corrosion testing and metallographic analysis of in vivo implants demonstrated a more uniform mode of corrosion for the solution treated alloy. We conclude that Zn–Ag alloys can be engineered through alloying to substantially reduce neointimal growth. The positive effect on neointimal growth can be further enhanced by dissolving the AgZn₃ precipitates in the Zn matrix to improve the corrosion uniformity. These findings demonstrate that neointimal-forming cells can be regulated by elemental additions and microstructural changes in degradable Zn-based implant materials. Statement of significance: The metallurgical engineering of bioresorbable zinc (Zn)-based medical alloys would greatly benefit from clarification of the relationships between material properties and biological responses. Here, selected binary and quinary Zn–Ag-based alloys underwent solution treatment (ST) to increase the solubility of Ag-rich phases within the Zn bulk matrix, yielding two different microstructures (one without ST and a different one with ST) with the same elemental composition. We found that applying a thermal treatment restores mechanical strength and mitigates the strain rate sensitivity of Zn–Ag alloys by dissolving AgZn₃ precipitates. Ag-rich nano-precipitates in Zn decrease biocompatibility, a phenomenon that can be counteracted by dissolving the AgZn₃ precipitates in the bulk Zn matrix.