Bone microenvironment-driven macro-galvanic coupling of Zn alloys: Mediating immune response and osteogenesis

Biodegradable metals exhibit heterogeneous degradation patterns within complex physiological microenvironments, which frequently culminate in premature implant sequestration or failure. While traditional research paradigms have prioritized enhancing material homogeneity, the impact of site-specific physiological variability remains insufficiently addressed. This study investigated the degradation kinetics and osteogenic efficacy of Zn-0.8Mg and Zn-0.8Fe alloys implanted into distinct anatomical sites: the medullary cavity and the bone matrix. Our findings reveal that microenvironmental fluctuations trigger macro-galvanic coupling within the Zn alloys, inducing localized crevice corrosion. The spatiotemporal flux of Zn 2+ was identified as a decisive factor in modulating bone regeneration. In the well-perfused medullary cavity, the Zn alloy functioned as a cathodic site, exhibiting suppressed degradation rates. This sustained Zn 2+ release within a pro-osteogenic therapeutic window, significantly enhancing bone volume; notably, the Zn-0.8Mg alloy elicited a 10-fold increase in new bone formation relative to pure Titanium (Ti) after one month. Conversely, within the transport-restricted bone matrix, the alloy acted as an anode, undergoing accelerated degradation. The resultant Zn 2+ overload triggered pro-inflammatory macrophage polarization and impaired osteoblast viability. Histological analysis at one-month post-implantation revealed am non-ossified zone surrounding the implants, measuring approximately 50 μm for Zn-0.8Mg and 100 μm for Zn-0.8Fe. These insights underscore that the implant microenvironment dictates the material's biological fate, providing new understanding for the design of next-generation, microenvironment-adaptive orthopedic implants. • Zn alloys across medullary cavity/bone matrix microenvironments formed a macroscopic galvanic couple. • Zn alloy corrosion accelerated in the bone matrix (anode) relative to the medullary cavity (cathode). • Crevice corrosion in the bone matrix accelerated the degradation process of Zn alloys. • Excessive Zn 2+ release from rapid bone-matrix degradation induced inflammation and impaired osteogenesis. • Microenvironmental conditions dominated over alloy composition in determining the degradation behavior and osteogenesis.