磁性羟基磷灰石纳米管涂层设计及其肽控释抗菌与骨整合

The poor bone integrity and bacterial infection may induce initial failure of titanium alloy after implantation. By mimicking the chemical composition and microstructure of bone matrix and considering the effect of micro-magnetic field on the cells and bone matrix, a composite coating composed of microporous TiO2 as an inner layer and Si- and Fe-codoped HA nanotubes as an outer layer is designed and prepared on Ti alloy. The HA nanotube layer is magnetic and degradable, and the release of loaded antimicrobial peptide can be controlled. The research interests of the project include: the formation mechanism of HA nanotubes, structure characterization and bond mechanism of the interfaces between the adjacent phases, the influence of structure of HA nanotube on its magnetism and degradation, the responses of cells and new bone tissue formation ability on the nanotube's structure, magnetism and ion releasing. After loading with antimicrobial peptide, the antimicrobial peptide releasing kinetics, antimicrobial behaviors, cells response and new bone tissue formation ability of the HA will also be clarified. By optimizing the structures of the composite coatings on the basis of the aformentioned investigations, it is expected to endow the composite coating with high bond strength, bioactivity, long-term antimicrobial effect and establish the fundamental of surface modification of metallic materials to improve their clinical functions.

针对钛合金植入体骨整合能力差及易细菌感染引起的种植早期失效，基于仿骨基质化学组成和几何构形的设计思想，结合微磁场对细胞及组织的作用效应，本项目在钛合金表面设计、构建“Si、Fe掺杂磁性可降解羟基磷灰石（HA）纳米管/TiO2”复合涂层并实现抗菌肽的可控释放；阐明Si、Fe掺杂HA纳米管的形成机理，揭示“HA纳米管/TiO2/钛”各界面的结合机制；研究HA纳米管结构与其磁学性能、降解性之间关系；探讨纳米管结构、离子释放及磁学性能对成骨相关细胞附着、功能表达及新骨形成之间的关系；揭示HA纳米管结构组态对抗菌肽释放动力学的影响规律及其抗菌行为的持续效应；阐明负载抗菌肽后纳米管对细胞、新骨形成量随涂层结构、种植时间的变化作用；提出钛合金表面呈高结合强度、生物活性、长期高效抗菌的复合涂层结构优化构建方案，为提升钛合金临床效能奠定基础。

本项目针对钛合金植入体由于骨整合能力差与宿主骨固定不稳以及植入早期、后期细菌感染等引起的种植失效，基于仿骨基质化学组成及几何构形的设计思想，结合微磁场对细胞及组织的作用效应，通过微弧氧化、水热处理、电化学处理、化学键合等关键技术，在钛表面获得了Fe掺杂的磁性TiO2为内层，Fe、Si掺杂的HA纳米阵为外层的复合涂层，并在HA纳米阵列表面物理吸附/化学接枝了抗菌肽；阐明了Fe掺杂TiO2的磁性形成机理：Fe掺杂进TiO2晶格形成Fe3+-Vo-Fe3+偶极子是TiO2显磁性的原因；揭示了磁性HA基面因晶格变形在电化学处理中发生选择性溶解的纳米管形成机制；揭示了纳米磁性粒子形成的微区磁场加快细胞分化，促进组织整合的作用效应；阐明了纳米阵列表面物理吸附及化学接枝抗菌肽的释放动力学及其抗菌行为的持续效应；阐明了负载抗菌肽后纳米阵列的抗菌性能及其对细胞、新骨形成量随涂层结构、种植时间的变化作用；提出钛表面呈高结合强度、生物活性、长期高效抗菌的复合涂层结构优化构建方案，为其满足临床应用奠定了基础。.研究结果发表论文16篇（3篇IF>10），授权国家发明专利6项，其中2项技术转让，培养博士生4人（毕业1人，在读3人），硕士生4人(毕业3人，在读1人)。