Antimicrobial Bioresorbable Mg-Zn-Ca Alloy for Bone Repair in a Comparison Study with Mg-Zn-Sr Alloy and Pure Mg

抗菌生物可吸收 Mg-Zn-Ca 合金与 Mg-Zn-Sr 合金和纯 Mg 的骨修复对比研究

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作者:Chaoxing Zhang, Jiajia Lin, Nhu-Y Thi Nguyen, Yuxing Guo, Changlu Xu, Catherine Seo, Edgar Villafana, Hector Jimenez, Yang Chai, Renguo Guan, Huinan Liu

Abstract

Magnesium-zinc-calcium (Mg-Zn-Ca) alloys have attracted increasing attention for biomedical implant applications, especially for bone repair, because of their biocompatibility, biodegradability, and similar mechanical properties to human bone. The objectives of this study were to characterize Mg-2 wt % Zn-0.5 wt % Ca (named ZC21) alloy pins microstructurally and mechanically, and determine their degradation and interactions with host cells and pathogenic bacteria in vitro and in vivo in comparison with the previously studied Mg-4 wt % Zn-1 wt % strontium (named ZSr41) alloy and Mg control. Specifically, the in vitro degradation and cytocompatibility of ZC21 pins with bone marrow derived mesenchymal stem cells (BMSCs) were investigated using both direct culture and direct exposure culture methods. The adhesion density of BMSCs on ZC21 pins (i.e., direct contact) was significantly higher than on pure Mg pins in both in vitro culture methods; the cell adhesion density around ZC21 pins (i.e., indirect contact) was similar to the cell-only positive control in both in vitro culture methods. Interestingly, ZC21 showed a higher daily degradation rate, crack width and crack area ratio in the direct exposure culture than in the direct culture, suggesting different culture methods did affect its in vitro degradation behaviors. When cultured with Gram-positive bacteria methicillin-resistant Staphylococcus aureus (MRSA), ZC21 reduced bacterial adhesion on the surface more significantly than that of ZSr41 and Mg. The in vivo degradation and biocompatibility of the ZC21 pins for bone regeneration were studied in a mouse femoral defect model. The in vivo degradation rate of ZC21 pins was much slower than that of ZSr41 alloy and Mg control pins. After 12 weeks of implantation in vivo, the ZC21 group showed the shortest gap at the femoral defect, indicating that ZC21 pins promoted osteogenesis and bone healing more than ZSr41 and Mg control pins. Overall, the ZC21 alloy is promising for bone repair, while providing antibacterial activities, and should be further studied toward clinical translation.

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