Biodegradable Zn-Li-Mn alloy to achieve optimal strength and ductility for bone implants.

Biodegradable zinc-based metals have received attention due to their strength, biodegradability, and desirable biocompatibility. However, the trade-off between strength and ductility has limited their use. Here, we designed a biodegradable Zn-Li-Mn ternary alloy with superior strength and ductility. The ultimate tensile strength (UTS) of Zn-0.4Li-xMn (x = 0.1, 0.4, and 0.8) alloys reached 438.74-469.96 MPa, similar to pure Ti, with elongation reaching 41.52%-54.91%, surpassing other Zn-Li-based alloys. We investigated the biodegradation behavior and osteogenic effects of the Zn-Li-Mn alloys both in vitro and in vivo. Immersion tests demonstrated that the alloys exhibited a more uniform degradation morphology with significantly less release of Zn²⁺ ion compared to pure Zn. Cytocompatibility, hemocompatibility, and histological analyses demonstrated their biosafety. In addition, Zn-Li-Mn alloy extracts significantly enhanced osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs), manifesting higher alkaline phosphatase activity, increased biomineralization, and elevated osteogenic gene expression. Zn-0.4Li-0.8Mn alloy showed the highest osteogenic activity in vitro. When implanted in rat femoral condyles, it demonstrated improved in vivo bone regeneration effects, exhibiting enhanced osteointegration. Transcriptomic analysis revealed that Zn²⁺, Mn²⁺, and Li⁺ ions released from Zn-Li-Mn alloy collectively activated the MAPK-ERK and Wnt/β-catenin signaling pathways, prompting osteogenic differentiation. These findings demonstrate the high potential of the Zn-0.4Li-0.8Mn alloy for bone implants. STATEMENT OF SIGNIFICANCE: 1. Biodegradable Zn-Li-Mn ternary alloy with superior mechanical strength and excellent ductility were designed. 2. Enhanced osteointegration were observed in Zn-0.4Li-0.8Mn implants in vivo. 3. Transcriptomic analysis revealed that the Zn²⁺, Mn²⁺, and Li⁺ released from Zn-0.4Li-0.8Mn collectively activated the MAPK-ERK and Wnt/β-catenin signaling pathways, enhancing osteogenesis.