Biodegradable porous zinc scaffolds for bone regeneration: multiscale architecture, degradation control, and osteo-immunomodulation

Biodegradable porous zinc (Zn)–based scaffolds have emerged as promising temporary orthopedic implants due to their moderate degradation rate, essential physiological role, and intrinsic osteogenic, antibacterial, and immunomodulatory functions. Interconnected porous architectures that mimic trabecular bone are critical for enabling cell infiltration, vascularization, and bone ingrowth. However, increased porosity and specific surface area inevitably accelerate corrosion and Zn²⁺ release, giving rise to tightly coupled trade-offs among mechanical integrity, degradation behavior, cytocompatibility, antibacterial efficacy, and immune responses. This review presents a mechanism-oriented and integrative perspective on biodegradable porous Zn scaffolds, emphasizing the intrinsic coupling between scaffold architecture, corrosion kinetics, and the evolving biological microenvironment. State-of-the-art fabrication strategies—including powder metallurgy, additive manufacturing, electrodeposition, and pressure infiltration—are critically analyzed with respect to how fabrication-induced architectural features dictate mechanical performance, degradation evolution, and the spatiotemporal distribution of Zn²⁺ ions. Recent advances in Zn-mediated osteo-immunomodulation are synthesized, highlighting how Zn²⁺ and its degradation products regulate macrophage polarization and inflammatory signaling, thereby coordinating downstream osteogenesis, angiogenesis, and antibacterial activity. Finally, key challenges—including degradation–healing mismatch, excessive local Zn²⁺ accumulation, inflammatory risks, and limited osseointegration are discussed, and future directions are outlined toward multiscale architectural engineering, immune-instructive surface functionalization, and programmable degradation. This review positions porous Zn scaffolds as active, immune-regulating biomaterials and provides design principles for the development of next-generation biodegradable orthopedic implants.