抑制镁合金非均匀降解的自愈合仿骨结构表层设计及其成骨效应

The obstacle for magnesium clinical use is their high degradation rates in physiological environment. Aiming at inhomogeneous degradation suppression and osseointegration efficiency enhancement of magnesium alloy, the project makes an effort to establish hybrid processing techniques of ultrasonic-microarc oxidation, hydrothermal treatment and vacuum-assisted physical absorption for surface modification of Mg alloys. With the key techniques, a bone-like structured novel bilayer coating with self-healing function, comprising degradation inhibitor-loaded MgO with double ions (Sr and carbonated ions) doped octacalcium phosphate (OCP) sealing pores as an inner layer and double ions-doped OCP nanorods with narrow interrod space as an outer layer, are designed and fabricated on Mg alloys. The research interests include: formation mechanism of double ions-doped OCP nanorods, structure characterization and bond mechanism of the interfaces between the adjacent phases, the inhibition effects of the coating on inhomogeneous degradation, degradation behavior of the inner and outer layers as well as its dependence on the structures of the layers, the effect on osteogenesis-related cell functions and osseointegration efficacy of the double ions-doped OCP nanorods. By optimizing the structure of the bilayer coating on the basis of the aforementioned investigations, it is expected to endow the coatings with high bond strength, high osseointegration capability and function of inhibiting inhomogeneous degradation of Mg substrate. It is the aim to enhance the fixation between the coated Mg implant and new bone and suppress degradation of Mg substrate to match the damaged bone healing.

针对镁合金降解过快制约其骨修复临床应用这一问题，着眼于镁合金非均匀降解抑制及其骨整合效力提升，利用超声辅助微弧氧化、水热生长及真空辅助物理吸附技术，在其表面设计并获得具有自愈合功能的仿骨结构涂层，其中涂层以负载降解抑制剂的双离子（锶、碳酸根离子）掺杂磷酸八钙（OCP）封孔氧化镁为内层，窄间距、双离子掺杂OCP纳米棒为外层；研究掺杂OCP纳米棒形成机理、各组相间界面结合机制，考察涂层对镁基体非均匀腐蚀的抑制效应，揭示涂层中内、外层降解行为及降解消失协同性与其结构组态间的关系，阐明双离子掺杂OCP纳米棒掺杂离子剂量及配比对成骨相关细胞、骨整合的作用效应，建立涂层呈高结合强度、高骨整合效力、降解消失协同性及抑制镁合金非均匀降解的优化构建方案，以实现增强镁基植入体与新骨结合及其降解与骨愈合匹配的目标。

本项目着眼于镁合金降解过快制约其骨修复这一临床问题，从物理构形及化学组元视角出发，构建镁合金表面涂层，在提升涂层耐蚀性的同时，赋予其免疫调变能力，使其具有强的骨整合效力，最终实现植入体降解和骨愈合协同。在物理构形方面，通过微弧氧化和水热处理在镁合金表面构建了三维羟基磷灰石（HA）纳米棒阵列/封孔MgO双层结构涂层，研究了涂层体内免疫调控效应并揭示其骨整合机制，阐明了涂层在体内的降解机制。相较于二维多微孔MgO涂层，HA纳米棒阵列能够显著上调抑炎因子，下调促炎因子，促进巨噬细胞向M2表型转化，使植体周围免疫微环境利于成骨，从而提升新骨生成量；HA纳米棒阵列能够显著促进骨髓基质干细胞（BMSCs）在植入早期分泌非胶原蛋白并诱导其矿化形成骨粘合线基质，矿化后的骨粘合线基质与HA纳米棒之间以机械铆合方式形成强界面结合，从而提升植体/骨早期固定度；该涂层在体内降解消失，而非从基体剥离，从而避免由涂层剥落诱发的溶骨及炎性反应。在化学组元方面，通过微弧氧化、旋涂及化学沉积方法在镁合金表面构建了负载免疫调控药物——姜黄素的载药自愈合涂层，局部电化学测试及浸泡实验检测结果显示涂层呈现强的自愈合性，能够在模拟体液长期浸泡过程中为镁合金提供长效保护；由于姜黄素的长效缓释，该涂层加速巨噬细胞由促炎M1表型向抑炎M2表型转化，提升BMSCs成骨功能，展现强的骨整合效力；上述作用均随涂层中降解抑制剂及姜黄素含量的增加而显著增强。研究表明，在涂层中通过元素掺杂、离子注入等方式负载金属离子或调控纳米棒阵列几何构形参量可使涂层在保持高骨整合性的前提下具有强抗菌性。优化结构及组分的镁合金表面涂层，有望克服镁合金临床应用瓶颈，使其满足骨固定钉/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论文6篇（影响因子大于10.0的论文1篇，大于5.0论文3篇），授权发明专利1项；参加学术会议并作口头报告7次；培养硕士生5人。