混合离子注入对椎间融合器表面涂层的细胞增殖和抗菌性的协同调控

When the fusion cage (Cage) implants into humans, the synergy between bone tissue regeneration and antibacterial effects is the key of raising the therapeutic effect in treating spinal degenerative diseases. But this goal is hard to achieve with current technologies. In this paper, titanium nitride coating (TiN) is firstly coated on the Cage surface in order to improve its abrasion-resistant and corrosion resistance while blocks the release of the toxic elements in Cage, such as aluminum (Al) and vanadium (V). Then, Zn+、Ag+、Cu+ mixed ions are implanted into the surface of nano-sized titanium nitride-coated fusion cage (TiN-Cage) via plasma immersion ion implantation technology (PIII), which may improve the histocompatibility and antibacterial property of the fusion cage at the same time. After the Zn+、Ag+、Cu+ ions implanted together into the TiN-Cage (Zn+/Ag+/Cu+-TiN-Cage), the bone cells may proliferate faster and the fusion rate may enhance greatly. Its antibacterial activity will also improve to adapt to clinical demand. Meanwhile, the mechanism analyses of biocompatibility based on the first-principle calculation between Zn+/Ag+/Cu+-TiN-Cage and specific binding sites of cell surface are calculated. And the interactions between Zn+/Ag+/Cu+-TiN-Cage and sulfhydryl groups or amino compounds are also calculated though the first-principle calculation. In a word, Zn+, Ag+ and Cu+ ions are implanted together into the TiN-Cage though multi-ion implantation in order to enhance the synergy between bone tissue regeneration and antibacterial effects of the fusion cage. So this study can provide valuable basis for enhancing the clinical effect and prolonging the lifetime of the fusion cage.

椎间融合器（Cage）植入人体后的骨组织生长和抗菌性的协同作用是其临床效果的关键，而目前的多种技术很难控制二者的协同改善。本项目预先把TiN涂覆在Cage表面，达到增强耐磨和耐蚀性，抑制有毒元素的释放；继而尝试利用等离子体浸没离子注入关健技术将不同离子（Zn+、Ag+、Cu+）混合注入到TiN-Cage，利用混合离子注入的协同作用调控并同时改善TiN-Cage的组织相容性和抗菌性，实现使其表面骨组织长入时间加快、融合率提高、抗感染性增强的协同效果；同时通过第一性原理探究经混合离子注入的融合器表面与接触细胞表面识别位点、细菌表面巯基或氨基化合物之间的相互作用规律，揭示其对细胞和细菌的调控机理。本项目利用混合离子注入技术结合TiN涂层保护，致力于控制椎间融合器临床使用中细胞增殖和抑菌的协同改善，预期为延长其使用寿命和提高临床效果提供一种新的表面改性工艺以及有价值的依据。

本项目采用等离子体浸没离子注入与沉积系统，首先在椎间融合器（Cage）基材（Ti-6Al-4V）表面沉积TiN涂层，然后进行Zn/Ag、Zn/Cu、Mg/Ag和Ca/Ag混合离子共注入修饰。.修饰后的TiN-Cage临界载荷达到467 mN，实现TiN薄膜与Ti-6Al-4V的良好结合，抗断裂性能良好；硬度达到21 GPa以上，弹性模量达到260 GPa，较Ti-6Al-4V硬度（5.94 GPa）提升了近3倍；模拟体液环境下耐腐蚀性提高，有效延长了Cage在生理环境中的生存时效。同时，由于TiN薄膜的包裹作用，相较Ti-6Al-4V，修饰后的Cage材料在体液环境下Al3+的析出量下降了一倍，V4+几乎不析出，起到了有效抑制毒离子释放的作用。使得修饰后的Cage材料达到增强耐磨和耐蚀性，抑制有毒元素的释放的课题设计目标。.研究通过Zn/Ag、Zn/Cu、Mg/Ag和Ca/Ag混合离子共注入实现了修饰后Cage表面骨组织长入时间加快、融合率提高、抗感染性增强的协同效果。同时，通过调控不同共注入离子比例及含量，筛选出协同提升Cage成骨活性与抗菌性最佳的Zn/Ag、Zn/Cu、Mg/Ag和Ca/Ag共注入样品。通过实验并结合基于密度泛函的第一性原理以及生化理论，获得致硬、耐腐蚀及生物相容性之间的相互关系，理解协同调控机理。.在研究还发现，相比Zn/Cu共注入，Zn/Ag共注入在改善TiN力学性能方面效果更优，这是因为相较Cu，Ag的原子半径更大，其通过固溶强化引起了更大的晶格畸变，进而增加位错运动阻力，使滑移更困难；而等剂量条件的Mg和Ca注入相比，Mg对骨组织生长和抗菌性二者的协同改善效果更好，这是由于Mg不仅自身具有一定的抗菌能力，其还能通过促进细胞外基质矿化和提升碱性磷酸酶活性，达到促进骨细胞增殖、黏附的作用。综上，本课题为延长Cage使用寿命和提高临床效果提供一种新的表面改性工艺以及有价值的依据。其中，在包覆TiN的Cage表面进行Zn/Ag，Mg/Ag共注入是协同改善Cage表面骨组织生长和抗菌性的优良选择。