高强度可降解Zn-Li-Ag合金内植物治疗感染性骨缺损的基础研究

感染性骨缺损的治疗仍是骨科医生面临的最大挑战之一，尤其是发生在承重部位的大段骨缺损。以自体骨为代表的传统骨替代材料因欠缺足够力学强度和持续抗菌活性，无法满足治疗需求。为寻求理想治疗手段，基于前期研究中已证实的可降解锌合金的抗菌和成骨活性，优选抗菌活性元素Ag和力学强化元素Li，设计制备出高强度可降解三元Zn-Li-Ag合金。Zn-Li-Ag合金内植物可于局部缓慢降解，释放Zn2+和Ag+，持续发挥杀菌效果，Zn2+的成骨活性可有效促进骨新生，最终完全降解消失，由新生骨原位替代，完成骨的修复重建。本研究将系统评估Zn-Li-Ag合金的材料性能、生物相容性、杀菌作用和成骨活性，探究其发挥生物功能的分子机制；并建立MRSA诱导兔桡骨感染性节段性骨缺损模型，于体内证实Zn-Li-Ag合金内植物防治感染性骨缺损的疗效。旨在通过革新骨科生物材料，为感染性骨缺损的治疗提供理想策略。

The treatment of infected bone defects, especially critical-sized defects at load-bearing sites, remains one of the greatest challenges faced by orthopedic surgeons. Traditional bone substitute materials represented by autologous bone cannot meet the therapeutic needs due to their lack of sufficient mechanical strength and continuous antibacterial activity. In order to find an ideal treatment strategy, based on the antibacterial and osteogenic activities of biodegradable zinc alloys confirmed in previous studies, Ag element with antibacterial activity and Li element with mechanical strengthening property were selected in this study to design and prepare high-strength biodegradable ternary Zn-Li-Ag alloys. Zn-Li-Ag alloys implant can degrade slowly in vivo, releasing Zn2+ and Ag+, and continuously exerting local bactericidal effects. The osteogenic activity of Zn2+ can also effectively promote bone regeneration. Eventually, it completely degrades and disappears, and is replaced by new bone in situ to complete the bone repair and reconstruction. The material properties, bactericidal activity, and osteogenic activity of Zn-Li-Ag alloy were comprehensively evaluated through in vitro materials, bacteriology, and cytology experiments, and the molecular mechanism of its biological function was explored. Thereafter, an MRSA-induced rabbit infected segmental radius defect model was established, to verify the efficacy of Zn-Li-Ag alloy implants for the prevention and treatment of infected bone defects in vivo. It aims to provide an ideal strategy for the treatment of infected bone defects through the innovation of orthopedic biomaterials.