钛铌合金生物力型下颌骨支架梯度结构的构建及表面成骨活性的优化

Mandibular reconstruction is confronted with the problems of insufficient autogenous bone and mismatch of stress distribution between titanium implants and mandible. By optimizing the structure of titanium scaffold and combining it with fibula, our team pioneered the concept of titanium biomechanical mandible (BMM). However, the elastic modulus of BMM is still significantly higher than that of human bone, resulting in stress shielding, and the bone bonding on the surface of the scaffold is not good. Based on the preliminary study that the new beta-phase Ti-Nb alloy with low modulus and high strength, and its porous permeable surface can promote bone formation, this project intends to further optimize the material method to prepare a new kind of mandibular scaffold material with gradient mechanical properties and good osteogenic active surface. By adding Zr, Sn and adjusting the metal ratio, the optimum elastic modulus of Ti-Nb alloy will be selected as the matrix material. The Ti-Nb+Ti-Fe dual-phase system wil be deposited on the surface of the matrix by magnetron sputtering, and the Ti-Fe phase will be de-alloying to obtain the porous surface structure of Ti-Nb with controllable thickness and porosity. In vivo and in vitro experiments wil be carried out to analyze the osseointegration of different surface morphologies and further explore its molecular mechanism. This project will systematically study the relationship between the structure and properties of the new Ti-Nb alloy material, lay the foundation for the clinical transformation of BMM, and provide new ideas and means for mandibular reconstruction.

下颌骨重建面临自体骨量不足、钛植入物与下颌骨应力分布不匹配的问题。课题组通过优化钛支架结构并与腓骨相结合，开创性的提出钛生物力型下颌骨（BMM）理念，然而BMM弹性模量仍显著高于人骨导致应力屏蔽，且支架表面骨结合不佳。基于新型β相钛铌（Ti-Nb）系合金具有低模高强特性，且其多孔通透表面有促成骨作用的前期研究，项目提出通过材料学方法进一步优化，制备一种新型具有梯度力学性能及良好成骨活性表面的下颌骨支架材料。通过添加锆、锡等元素调整金属比例筛选最优模量钛铌合金作为基体材料；在此基体表面通过磁控溅射沉积“Ti-Nb+Ti-Fe”双相体系，去合金化消解Ti-Fe相从而获得厚度及孔隙率可控的Ti-Nb多孔通透表面结构；通过体内外实验分析不同表面形貌骨结合情况并深入探讨其分子机制。本课题将系统研究该新型钛铌合金材料结构与性能之间的关系，为BMM的临床转化奠定基础，并为下颌骨重建提供新思路和新手段。

钛生物力型下颌骨（BMM）是解决下颌骨重建过程中单层腓骨高度不足问题的一种装置，项目组前期从生物力分析的角度，从支架结构设计上改善了BMM的应力传导性能，一定程度上改善了传统钛板与下颌骨应力分布不匹配的问题。.然而，由于BMM为纯钛金属，钛的弹性模量（约108 Gpa）显著高于自然骨（0.3~20 GPa），导致“应力屏蔽”；BMM在植入后即参与下颌骨运动，行使咀嚼等一系列负重功能，BMM与下颌骨断端之间成骨能力较弱，往往导致骨不愈或纤维愈合。基于上述瓶颈，本项目根据不同合金比例，分别选择Ti-40Nb（二元），Ti32Nb-4Sn（三元）和Ti-24Nb-4Zr-8Sn（四元）三组合金，结果显示三种合金均为β相且弹性模量均较低，分别为：30.9Gpa，51.9Gpa，48.2GPa，显著低于纯钛的弹性模量。通过“磁控溅射&去合金化”相结合方法，有效控制多孔层厚度和孔隙率，制备出的多孔结构的弹性模量分别为24 GPa和37 GPa，接近人骨弹性模量（10-30 GPa）范围，达到植入物植入人体所需的表层模量的要求。通过喷丸、双酸酸蚀、碱热处理的复合工艺，在纯钛及钛合金表面引入了具有超亲水性的微纳分级多孔结构，并证实这种结构有益于羟基磷灰石沉积，说明了复合工艺能有效提升钛合金材料表面的生物相容性。SLA+AT钛合金表面微纳分级多孔结构呈现出了双峰形态，即微米结构和纳米孔尺寸都分布在某范围附近；Ti40Nb样品表面的纳米孔径平均尺寸最大，约88.2nm；Ti2448样品表面的纳米结构平均尺寸最大，约2.21μm。润湿性分析发现在复合工艺处理后Ti40Nb、Ti32Nb4Sn和Ti2448表面都变得超亲水，而纯钛材料在经过复合工艺处理后的亲水性不如钛合金。羟基磷灰石沉积能力分析发现SLA+AT Ti2448样品表面的羟基磷灰石沉积能力最强、生物相容性能最好，这是因为Ti2448表面具有更大的微米结构、纳米孔以及更厚的粗糙层，而这样的结构更有利于吸附、存贮营养物质。本课题研究结果为改良BMM的力学性能及材料表面处理工艺提供了理论基础。