From rational alloying to coupled regeneration: An additively manufactured biodegradable Zn-2.5Cu-1Mn scaffold orchestrating immunomodulation, angiogenesis, and osteogenesis.

The development of biodegradable zinc (Zn) implants with adequate mechanical strength and tailored degradation for bone defect repair remains challenging. Alloying is a common strategy to enhance the performance of biodegradable Zn. While binary systems have been extensively studied, a ternary alloy design may enable more comprehensive property optimization. This study proposes a novel ternary alloy design philosophy for a porous Zn-Cu-Mn scaffold fabricated via selective laser melting (SLM). The addition of Cu and Mn synergistically enhances both the mechanical properties and the degradation rate of the scaffolds. After systematic optimization and screening, the Zn-2.5Cu-1Mn scaffold achieves an optimal balance between mechanical properties and degradation rate. The controllable degradation behavior maintains Zn2+ concentrations within an optimal range for osteogenesis. The scaffold orchestrates a pro-healing immune microenvironment by polarizing macrophages toward the M2 phenotype and concurrently enhances vascularization. Subsequently, bone regeneration is stimulated via paracrine coupling and direct activation of the Wnt/β-catenin pathway. In a rabbit femoral defect model, the scaffold exhibits excellent bone regeneration. This work demonstrates that rational ternary alloying achieves the multifunctional integration of enhanced mechanical properties, controllable degradation characteristics, and the coupling of immunomodulation-angiogenesis-osteogenesis within a Zn-2.5Cu-1Mn scaffold, providing a potent paradigm for designing intelligent biodegradable metallic implants that dynamically orchestrate the bone healing process.