基于力学强度完整与骨愈合协同的镁合金生物改性机制研究

The high degradation rate in physiological environment and consequent loss in the mechanical integrity of magnesium alloys limited their orthopedic applications. To overcome the drawbacks, the project makes an effort to establish hybrid processing techniques of microarc oxidation, hydrothermal treatment and ion implantation for surface modification of magnesium alloys. With the key techniques, novel bilayer coatings composed of Ce-doped MgO with multicomponents (including Sr、Zn、Mg、carbonated ions) doped hydroxyapatite (HA) sealing pores as an inner layer and multicomponents-doped HA nanorods carrying Ag nanoparticles as an outer layer, are designed and prepared on magnesium alloys. The research interests of the project include: the formation mechanism of multicomponents-doped HA nanorods, structure characterization and bond mechanism of the interfaces between the adjacent phases, degradation behavior of the nanorod-like multicomponents-doped HA and Ce-doped MgO layers and its dependence on the structure of the layers as well as degradation and mechanical strength loss of magnesium alloys, the effect of 3D nanorod-like topography and antimicrobial components on the new bone formation ability and response of cells and bacterial. By optimizing the structure of the bilayer coatings on the basis of the aforementioned investigations, it is expected to endow the coatings with high bond strength, bioactivity, antimicrobial effect and the function to depress the loss in the mechanical strength of magnesium alloys. It is the aim to enhance the early fixation between the coated magnesium alloy implant and bone and keep its mechanical integrity during the healing of damaged bone.

针对镁合金降解速率过快对其骨修复临床应用的制约，通过攻克微弧氧化、水热生长及离子注入关键技术，在镁合金表面设计并获得以多组元（Sr、Zn、Mg、碳酸根离子）掺杂HA封孔的Ce掺杂MgO为内层、负载银纳米粒子的多组元掺杂HA纳米棒为外层的复合涂层，研究多组元掺杂HA纳米棒的形成机理、各组相间界面的结合机制，揭示多组元掺杂HA纳米棒和Ce掺杂MgO封严层的降解行为、降解消失协同性与其结构组态的关系，及其与镁合金降解和力学强度退化之间的关系，阐明纳米棒三维构形几何参量及其负载杀菌组分对细胞、细菌和新骨形成的作用效应与机制，建立复合涂层呈高结合强度、生物活性、抗菌性、降解消失协同性和抑制镁合金强度退化的优化构建方案，以达到增进镁基植入体早期固定度及其降解与骨愈合匹配的目的。

镁合金降解过快制约其骨修复临床应用。本项目发明了微弧氧化-水热生长技术，在镁表面制备了羟基磷灰石（HA）纳米棒/封孔氧化镁（MgO）双层结构涂层，其中HA纳米棒直接生长于MgO基质，与基面呈垂直取向，棒间距及直径分别约为70和90 nm，并且封堵了内层MgO中孔隙。阐明了HA纳米棒的水热生长机理：HA纳米棒形核是由MgO层中掺杂的钙、磷离子由涂层内部向外表层迁移并在最外表层达到过饱和状态，同时与水热溶液中的羟基结合而成，而其生长所需要的钙离子则主要来源于水热溶液中Ca-EDTA的热解离。体内外降解研究表明，MgO涂层和双层结构涂层以均降解方式消失，且双层结构涂层对基体的抗蚀保护作用显著高于MgO涂层，使镁基体长期保持力学完整。揭示了纳米棒阵列构形几何参量（棒间距、取向和直径）对成骨相关细胞功能表达的调控作用及机制，发现纳米构形几何参量可显著调控其细胞响应行为；相比于MgO涂层，HA纳米棒/封孔MgO涂层显著增强了成骨细胞附着、增殖、分化和细胞外基质矿化。兔骨中种植实验结果表明，涂覆双层结构涂层的镁植入体能够显著下调其周围骨中的促炎及破骨相关基因，上调抑炎和成骨相关基因，进而使其周围的新骨生成量、新骨与植入体的接触率均显著高于MgO涂层镁植入体；HA纳米棒阵列与非胶原蛋白矿化形成的骨粘合线基质之间是以机械铆合方式结合，增强了植入体与宿主骨的固定度。研究表明，在涂层具有高骨整合能力前提下，通过元素掺杂、离子注入及物理吸附等方式负载金属离子或抗菌肽等抗菌剂，可使涂层具有强抗菌性。优化的双层涂层结构，具有高的结合强度、耐蚀性和骨整合能力，有望克服镁合金临床应用瓶颈，使其满足骨折（断）用固定钉/柱及脊柱融合器等临时性骨植入器件功能要求。本项目发表SCI收录论文24篇（其中影响因子大于3的论文20篇），授权发明专利4项；在国际、国内学术会议上作邀请报告8次；培养毕业博士生5人，毕业硕士生6人。