Structure-property-bioresponse correlation in Zr-based metallic glasses: from glass-forming ability to corrosion resistance and gene expression

• Ni- and Cu-free Zr-based metallic glasses designed using Pd, Pt, Au as substitutes. • GFA, microstructure, and corrosion behavior optimized for implants. • EIS reveals strong passive-film formation, especially in Zr–Pt and Zr–Pd alloys. • Cytocompatibility and gene-expression assays show no COX2/PTGES2 activation. Demand for orthopedic and dental implants continues to grow, driven by an aging population and traumatic injuries. Although current implant alloys have achieved clinical success, challenges related to ion release, inflammation, and long-term durability persist. To address these concerns, we developed three novel, biocompatible Zr-based metallic glasses free of toxic elements: Zr 66.5 Pd 16.5 Al 10 Fe 5 Ti 2 , Zr 66.5 Pt 16.5 Al 10 Fe 5 Ti 2 , and Zr 66.5 Au 16.5 Al 10 Fe 5 Ti 2 , fabricated via melt spinning. Their glass-forming ability, structural, thermal, and electrochemical properties were systematically evaluated, demonstrating high thermal stability and corrosion resistance suitable for biomedical applications, and indicating their potential use as intramedullary implants. Cytocompatibility was assessed by exposing human bone-marrow-derived mesenchymal stromal cells to alloy supernatants, which showed no adverse effects on metabolic activity or viability. The inflammatory response was investigated by analyzing COX2, PTGES2, and VEGF expression in human gingival fibroblasts. Notably, despite the conventional classification of Pd and Pt ions as pro-inflammatory, both Pd- and Pt-containing alloys downregulated inflammatory markers, similar to Au-containing alloys. These results indicate that immune modulation depends not only on elemental identity but also on ion release kinetics and structural context. Taken together, the results demonstrate that integrating corrosion behavior, cytocompatibility, and molecular assays provides a coherent framework for the rational design of immunologically safe metallic-glass implants.