医用镁合金表面钙磷涂层微纳结构的构建及其降解和成骨效应的研究

The aim of this project is to solve the problem of rapid degradation of the magnesium alloy used for bone internal fixation materials in bone repairing process, whereas calcium phosphorus coating with micro/nano structure will be investigated. Based on the fact that F ion can promote the orientation growth of hydroxyapatite and the structure of CaP coatings can be regulated by the templating agents, it is proposed to prepare micro/nano constructed coating on magnesium alloys by laser processing technology combined chemical conversion and hydrothermal methods. The research focuses on the adjusting of the nucleation, orientation growth and crystal phase of CaP, as well as the construction mode and mechanism of micro/nano structured coatings. In order to reveal the intrinsic relation between micro/nano structure and corrosion degradation, and then explore the effect of micro/nano structure on the osteogenesis properties, the mechanical attenuation behavior, degradation rule and biological properties of the coated magnesium alloys in vitro and in vivo were also studied. The ultimate goal of this project is to obtain the key factors for adjusting the degradation rate of micro-nano structure coating and the function of the osteogenesis, so as to achieve the micro/nano structured CaP coating coated magnesium alloys with controllable degradation rate, mechanical supporting and rapid osteogenesis. This study is of great significance on providing theoretical direction and technical support for the research and development, and the clinical experiments of biodegradable coated Mg alloys as bone internal fixation materials.

针对用于骨科内固定的可降解镁合金在骨修复过程中的降解速度过快的问题，本项目以微纳结构钙磷CaP涂层为研究对象，依据F离子具有促进晶体取向生长的习性，以及模板剂对CaP涂层结构的调控作用，拟将激光加工、化学转化法（HF腐蚀）和水热法相结合，在镁合金基体上制备出具有较强结合强度的微纳多级结构的CaP涂层。重点研究CaP晶相的成核、取向生长、晶型的调控因素，以及涂层微纳结构的构建过程、模式和机理。通过体外模拟和动物体内植入对比实验，研究微纳结构涂层镁合金的降解规律、力学性能衰减行为和生物性能，阐明微纳结构与腐蚀降解之间的本质关联，进而揭示微纳结构对成骨的作用机制。获得调控微纳结构涂层镁合金降解速率及影响成骨功能的关键因素，实现CaP涂层镁合金的可控降解，从而满足骨修复对涂层镁合金植入体力学支撑、降解周期和快速成骨的临床要求，为涂层镁合金骨科内固定材料的研发和临床实验提供理论基础和技术支持。

涂层改性镁合金因其具有与自然骨相匹配的力学性能，良好的可降解性及生物相容性，有望成为新一代可降解硬组织修复植入材料。但植入后涂层出现开裂、脱落，使镁合金基体快速降解，引起析氢、局部pH值波动、植入体力学支撑功能丧失等问题，将直接影响植入体与宿主间的界面结合，最终导致植入失效。本项目将酸碱预处理与辅助水热法相结合，在镁合金上制备粗糙度可控的微纳结构钙磷涂层，揭示了微纳结构与腐蚀降解之间的内在关系，及对成骨性能的影响，探究了钙磷涂层镁合金在体内外的降解规律和生物特性。.采用碱处理结合水热法在镁合金上制备的微纳结构HA涂层，与镁合金基体之间形成强的界面结合，在模拟体液中，涂层镁合金具有优异的耐腐蚀性能。试样浸泡147天之后其降解速率仍低于0.5 mm/y；HA涂层镁合金骨钉，浸泡154天，整体形貌完整，没有出现局部腐蚀，pH值一直稳定在7.5左右，表面形成了连续的矿化层，表明微纳结构涂层能够快速诱导磷灰石形成，具有良好的矿化能力。降解速率满足镁合金作为可降解植入材料的体外降解要求。.微纳结构HA涂层表面的粗糙度在调节细胞行为中起到关键作用，纳米针状HA构成的微纳结构涂层比相应纳米片状HA更有助于MC3T3-E1成骨细胞的分化。植入实验表明：微纳结构HA涂层能够促进新骨的生成，加快骨缺损的愈合。与没有涂层试样相比，植入4周便呈现较快的成骨表象。植入6个月后，成骨效果非常明显，骨痂有规律的形成，将植入骨板完全包裹。无涂层的骨板和骨钉周围仅有少量骨痂形成，骨板和骨钉腐蚀明显，但保持较为完成的外形。镁合金骨板骨钉在模拟体液中的降解速率和规律与体内植入实验结果有很大差异，因此不能直接用模拟体液中的实验数据指导体内植入实验的设计，体内的相关腐蚀机理有待深入研究。本项目研究成果可为钙磷涂层改性镁合金植入器件的制备和临床实验提供大量的实验数据和丰富的理论依据，对加快其临床应用具有重要的参考价值。