多孔钛合金孔壁表面力电转换涂层构建及其骨生长响应机制

The porous titanium alloys have exhibited their superiority as load-bearing metal implants. But its application is still constrained by the poor bone ingrowth, especially in deep part of the implants. Although the surface modification have provided a great many methods, the problem has not been resolved yet. Basing on the characteristics of endogenous electric field generated by mechano-electric transduction which could regulate the osteogenitic process under physiology condition, the research group will focus on the reconstruction of this mechano-electric transduction in porous titanium alloys. By tackling a series technical difficulties, a hydrothermal route will be used to get a nanoparticle barium titanate ceramic coatings, by which the endogenous electric field can be generated in a mechano-electric transducting way in vivo. The generated endogenous electric field will then optimize the bone ingrowth. Meanwhile, we will study the relationship between hydrothermal growth and interface reinforcement in the inner part of material and the related mechanism. The mechanism of coating thickness, grain size and phase composition affecting the mechano-electric transduction will also be studied. Then, through compressing cultivation of osteoblast in vitro, implantation in vivo and finite-element analysis, the effect of bone healing and mechano-electric transduction on nanoparticle barium titanate ceramic coatings will be observed and the related mechanisms will be revealed. Hence we could provide a new method for endogenous electric field construction and solve the problem of poor bone ingrowth into the porous titanium alloys.

多孔钛合金作为承重部位骨缺损修复替代优势材料，其应用效果仍受到内部孔隙骨长入不良的影响，现有表面活性涂层改性技术尚未有效解决这一难题。基于生理状态下，骨组织具有力电转换形成内生电场调控骨形成的特性，本项目针对多孔钛合金孔隙内部力电转换机制缺失的科学问题，拟通过攻克水热生长关键技术，在多孔钛合金孔壁表面设计并构建纳米粒状钛酸钡压电陶瓷涂层，在应力刺激下，发挥力电转换效应，形成有利新骨长入的内生电场。研究涂层的水热生长及其与多孔钛合金孔壁界面结合强化机制，探讨涂层晶粒尺度、物相组成、涂层厚度等结构组态对纳米钛酸钡力电转换效能的影响规律；通过成骨细胞体外加压培养、不同受力动物模型体内植入和有限元分析，揭示多孔钛合金孔壁表面纳米钛酸钡涂层改性的力电转换效应与孔隙内部骨形成关系，阐明相关骨生长响应机制，为多孔钛合金孔隙内部内生电场构建提供新方法，有效解决多孔钛合金内部孔隙骨长入难题。

多孔钛合金具有良好的生物相容性和力学特性以，同时骨组织长入材料内部后形成的锁固结构更有利于材料的稳定。但钛合金不具生物活性，导致孔隙深部骨长入不佳。钛酸钡压电陶瓷能够实现力-电信号的转换而被广泛关注。人体骨骼同样可感受环境力学刺激并进行力-电信号的转换形成内生电场，进而电信号调节相关细胞功能，从而促进新骨形成。本项目在前期研究基础上，通过水热合成法将钛酸钡纳米颗粒制备于多孔钛合金表面及内部，使该复合材料兼具钛合金的力学性能和钛酸钡的力电转换性能，进一步诱导新骨和血管长入孔隙深部，加强骨与材料的结合。通过能谱分析以及X射线衍射仪验证了水热合成可成功将钛酸钡制备在钛合金表面。通过压电力显微镜证实复合材料具有力电转换性能。通过体外细胞实验证实该复合材料可有效促进骨髓间充质干细胞(MSCs)和人脐静脉内皮细胞(HUVECs)增殖与迁移，同时可促进MSCs成骨分化及HUVECs成血管相关蛋白表达。在体内羊椎间融合器植入模型中，该复合材料通过压电效应可有效促进材料内部骨长入及材料周围和内部血管生成。因此，多孔钛合金表面生物活性钛酸钡涂层修饰可被用于骨植入物，能够有效促进骨形成和骨整合。