Biodegradable Zn‐5Dy Alloy with Enhanced Osteo/Angio‐Genic Activity and Osteointegration Effect via Regulation of SIRT4‐Dependent Mitochondrial Function

作者：Yue Han, Xian Tong, Runqi Zhou, Yilin Wang, Yuge Chen, Liang Chen, Hong Xin-hua, Linmei Wu, Zhiqiang Lin, Yichi Zhang, Xuejia Zhang, Chaoming Hu, Bin Li, Yifan Ping, Zelin Cao, Zhou Ye, Zhongchen Song, Yuncang Li, Cuié Wen, Yongsheng Zhou, Jixing Lin, Shengbin Huang · 发表于：Advanced Science · 年份：2024 · DOI：10.1002/advs.202307812 · 被引用次数：19 · 研究领域：Bone Tissue Engineering Materials、Orthopaedic implants and arthroplasty、Titanium Alloys Microstructure and Properties

Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.