Metabolic Osteoimmune Biodegradable Zn–Mn Alloys: High Strength‐Ductility and In Situ Vascular‐Osteogenic Coupling

Abstract Driven by the demand for sustainable, safe, and cost‐effective medical materials, design of biodegradable metals increasingly aims to achieve higher strength and biofunctionality with less alloying. This study proposes a high strengthening‐efficiency (high‐SE) design strategy and develops novel Zn‐0.8Mn‐0.1Mg and Zn‐0.8Mn‐0.1Li alloys. With total alloying additions below 1 wt.%, these alloys achieve yield strength of 369–397 MPa, elongation of 42–57%, and remarkable strengthening efficiency (SE) of 6.4–6.8. These SE values represent the highest level among high strength‐ductile Zn alloys (YS > 300 MPa, EL > 40%). Benefiting from the synergistic release of Zn 2+ , Mn 2+ , and Li + /Mg 2+ ions, both the alloys exhibit superior antibacterial activity, cytocompatibility, controlled degradation rates, and in vivo osteogenesis, demonstrating excellent degradation‐osteogenesis coupling effect. Notably, Zn‐0.8Mn‐0.1Mg further enhances osteogenesis by activating the PI3K/Akt/HIF‐1α signaling axis, which coordinates cascades of immunomodulation (e.g., IGF2, P2rx5), anti‐inflammation (e.g., Nfkbia inhibition), and cellular energy metabolism (e.g., Ndufaf3), resulting in a more pronounced osteogenic effect. This work establishes a new paradigm for high‐efficiency alloy design, achieving simultaneous breakthroughs in mechanical and biofunctionality, offering a promising framework for next‐generation Zn‐based orthopedic implants.