钛微弧氧化涂层构形与区域中药成分/壳聚糖水凝胶负载的骨结合机制

The poor osseointegration and bacterial infection for titanium implants could significantly compromise their applications in load-bearing bone repair and replacement. Microarc oxidation coating on Ti implant can benefit osseointegration, but can't avoid the stress shielding effect between bone and implant. Based on this conflict, we develop a new technology of microarc oxidation including corrosion of NO3- during the process. Associating with post hydrothermal treatment, a novel and multi-scale structural microarc oxidation coating with nano-scale HA rods, micro-scale pores and the traditionally sub-micro scale porous surface is formed on Ti. The effect of parameters on the structures of micro-scale pitting pores on Ti substrate and the nano-scale HA rods on coating surface will be explored. The regulation mechanism for the mutile-scale structure on microarc oxidation coating will be disclosed. The influence of chemical grafted micro-scale porous structure on the drug releasing and antibacterial behavior of the regionally loaded herbal ingredients/chitosan hydrogel in micro-scale pores will be studied. In addtion, the synergistic effects of the regionally loaded herbal ingredients/chitosan hydrogel and the multi-scale structurally designed microarc oxidation coating on the abilities such as cell behavior, osteogenesis expression and osseointegration will be realized. In order to facilitate the microarc oxidized titanium to be used in clinic, a project to gain a microarc oxidation coating with excellent antibacterial ability, osseointegration and bone bonding strength will be proposed.

本项目着眼于承力骨的修复与替换问题，针对钛种植体与骨组织结合差、易细菌感染的不足，立足于协调承力骨修复与微弧氧化钛种植体应力屏蔽效应的矛盾，通过攻克NO3¯离子腐蚀微弧氧化技术、结合水热后处理方法，对钛表面常规亚微米多孔结构微弧氧化涂层进行微米（大孔）与纳米尺度（磷灰石纳米棒）构形。探索钛表面腐蚀大孔（覆盖率、孔径和深度）及涂层表面磷灰石纳米棒（直径、长度和间距）结构与工艺参量之间的内在联系，揭示微弧氧化涂层的多尺度构形机制；研究经化学修饰的微米多孔结构对大孔区域内负载中药成分/壳聚糖水凝胶药物控释及抑菌作用的影响，揭示多尺度构形微弧氧化涂层与区域负载中药成分/壳聚糖水凝胶对成骨相关细胞行为、功能表达及骨整合的协同影响机理，提出钛种植体表面微弧氧化涂层呈优异抑菌能力、骨整合能力和骨结合强度的构建方案，为其临床应用奠定基础。

本项目着眼于承力骨的修复与替换问题，针对钛种植体与骨组织结合差、易细菌感染的不足，立足于协调承力骨修复与微弧氧化钛种植体应力屏蔽效应的矛盾，提出了对微弧氧化钛种植体进行表面构形及区域药物负载使其呈现优异抑菌能力和骨整合能力的构建方案。. 为了克服种植体与骨组织的整合难点，采用NO3−离子微弧腐蚀技术，并结合传统微弧氧化工艺，对微弧氧化钛种植体进行了亚毫米/微米双级孔隙结构构建。揭示了微弧腐蚀过程中电流强度对钛基底微弧氧化能力和NO3−离子腐蚀能力的调控机理；探讨了定点腐蚀过程中能量密度对钛表面腐蚀大孔结构的调控机制；明确了微弧氧化钛种植体表面亚毫米多孔结构可诱导骨组织长入，形成机械啮合作用的力学强化机制。. 针对水热处理生成HA纳米棒与涂层结合较差的缺点，提出了在微弧氧化钛植入物表面水热处理构建与TiO2氧化层结合良好的SnO2纳米棒状膜层。通过TiO2和SnO2晶体能带结构的差异在涂层表面形成内建电场刺激以赋予涂层生物活性；阐明了水热处理过程中助剂改变种植体表面形核位点数量调控SnO2纳米棒结构的生长机制；揭示了SnO2-TiO2陶瓷涂层内建电场刺激促进磷灰石沉积和骨胶原生长的骨性结合机制。. 针对钛种植体易细菌感染的不足，为避免药物载体对涂层生物活性的影响，提出在多级构形的微弧氧化钛种植体表面区域化负载载药壳聚糖水凝胶。阐明了改变微弧氧化电解液溶质浓度可调控HA纳米棒结构的水热生长机制；揭示了硅烷化和戊二醛处理对生物活性涂层和壳聚糖水凝胶的化学接枝结合强化作用；明确了区域化壳聚糖水凝胶药物负载更加有利于涂层生物活性和抗菌能力表达的微区快速药物控释降解机制。. 自立项以来，课题组共发表SCI论文4篇；申请国家发明专利12项，其中已授权3项。培养硕士生3人，本科生5人。期间1人次进行国际访学交流。各项指标基本实现了项目申请时的预期成果。