Shen Danni, Li Yahong, Shi Jiahui, Zhang Ting, Nie Jing-Jun, Chen Dafu, Xia Dandan, Zheng Yufeng
Department of Dental Materials, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices& Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China; School of Materials Science and Engineering, Peking University, Beijing 100871, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining 314400, China.
Department of Dental Materials, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices& Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China.
Acta Biomater. 2025 Jun 1;199:483-499. doi: 10.1016/j.actbio.2025.04.056. Epub 2025 May 1.
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 Zn 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 Zn, Mn, 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 Zn, Mn, and Li released from Zn-0.4Li-0.8Mn collectively activated the MAPK-ERK and Wnt/β-catenin signaling pathways, enhancing osteogenesis.
可生物降解的锌基金属因其强度、生物降解性和良好的生物相容性而受到关注。然而，强度和延展性之间的权衡限制了它们的应用。在此，我们设计了一种具有卓越强度和延展性的可生物降解锌-锂-锰三元合金。Zn-0.4Li-xMn（x = 0.1、0.4和0.8）合金的极限抗拉强度（UTS）达到438.74-469.96兆帕，与纯钛相似，伸长率达到41.52%-54.91%，超过其他锌-锂基合金。我们在体外和体内研究了锌-锂-锰合金的生物降解行为和成骨作用。浸泡试验表明，与纯锌相比，该合金呈现出更均匀的降解形态，锌离子释放量显著减少。细胞相容性、血液相容性和组织学分析证明了它们的生物安全性。此外，锌-锂-锰合金提取物显著增强了人骨髓间充质干细胞（hBMSC）的成骨作用，表现为更高的碱性磷酸酶活性、增加的生物矿化和升高的成骨基因表达。Zn-0.4Li-0.8Mn合金在体外显示出最高的成骨活性。当植入大鼠股骨髁时，它在体内表现出改善的骨再生效果，显示出增强的骨整合。转录组分析表明，从锌-锂-锰合金释放的锌、锰和锂离子共同激活了MAPK-ERK和Wnt/β-连环蛋白信号通路，促进成骨分化。这些发现证明了Zn-0.4Li-0.8Mn合金在骨植入物方面具有很高的潜力。重要意义声明：1. 设计了具有卓越机械强度和优异延展性的可生物降解锌-锂-锰三元合金。2. 在体内观察到Zn-0.4Li-0.8Mn植入物的骨整合增强。3. 转录组分析表明，从Zn-0.4Li-0.8Mn释放的锌、锰和锂共同激活了MAPK-ERK和Wnt/β-连环蛋白信号通路，增强了成骨作用。
