多孔钛孔壁纳米纤维化结构设计及其皮下软组织整合机制与抗菌性能

The poor soft tissue intergrity of titanium alloy significantly limits its application in percutaneous implant.A Ti post with a compact inner and a porous surface is designed armed at the sub-epithelial soft tissue, and it is fabricated by selective laser melting process. The project makes an effort to establish hybrid processing techiques of microarc oxidation, alkaline hydrothermal treatment and "dipping-calcining" for surface modfication of titanium alloy. With the key techniques, novel composite coatings composed of Zn-doped microporous TiO2 as an inner layer and sodium titanate nanofibers carrying CuO nanoparticles as an outer layer, are designed and prepared on the porous walls of macroporous Ti substrates.The research interests of the project include: the formation mechanism of sodium titanate nanofibers, structure characterization and bond mechanism of the interfaces between the adjacent phases, the influence of nanofiber and TiO2 on the CuO and Zn releasing kinetics and antimicrobial behaviors, the effect of 3D nanofibers topography and antimicrobial components on the new soft tissue formation ability and reponse of cells. 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, biactivity, long-term antimicrobial effect. It is the aim to enhance the fixation between the coated percutaneous Ti implant and sub-epithelial soft tissue, reduce epithelial downgrowth,avulsion and infection, and increase the sevice life.

着眼于钛合金表面皮肤组织整合性差对其作为经皮种植体长效使用的制约，针对真皮层及皮下组织，采用选区激光熔化快速成型技术制备的内层致密、外层多孔的钛合金为基材，通过攻克微弧氧化-热碱处理-浸渍煅烧的复合工艺，在多孔钛孔壁表面设计了以Zn掺杂的多孔TiO2为内层、负载CuO纳米粒子的钛酸钠纳米纤维为外层的复合膜层；研究复合膜的形成机理、各组相间界面的结合机制；探讨钛酸钠纳米纤维、TiO2结构对CuO、Zn释放动力学的影响规律及其抗菌行为的持续效应；阐明纳米纤维三维构型几何参量及负载抗菌组分对细胞、内孔壁皮下软组织形成的作用效应及机制；提出多孔钛孔壁表面呈高结合强度、生物活性、长期高效抗菌的“纳米CuO/钛酸钠纳米纤维/掺锌TiO2”复合涂层的结构优化构建方案，以达到促进多孔钛内孔壁与真皮及皮下组织形成牢固结合，降低上皮移行、撕裂以及细菌感染引起的种植体失效，提高服役寿命的目的。

钛合金表面皮肤组织整合性差制约了其作为经皮种植体临床使用，本项目采用选区激光熔化快速成型技术制备的内层致密、外层多孔的钛合金为基材，发明了微弧氧化-热碱处理-浸渍煅烧的复合工艺，在多孔钛孔壁表面设计并得到了以Zn掺杂的多孔TiO2为内层、负载CuO纳米粒子的钛酸钠纳米纤维为外层的复合膜层；揭示了钛酸钠纳米纤维的形成机理:随着水热时间的延长，钛酸钠由纳米片-纳米针-纳米纤维逐渐转变，纳米阵列的取向由垂直转变为平铺于涂层表面，纳米纤维的形成符合“溶解-沉积”生长机制。建立了Cu2+、Zn2+离子释放动力学与其在涂层中掺杂量的关系；揭示了Cu2+及Cu2+、Zn2+复合离子的促皮肤组织细胞响应及长期高效抗菌机制，发现在Cu2+、Zn2+共同作用时，细胞行为对Cu2+浓度变化更敏感；研究了钛酸钠纳米纤维对Zn释放动力学的影响规律及其抗菌行为的持续效应；阐明了纳米纤维三维构型几何参量及负载抗菌组分对细胞、皮下软组织形成的作用效应及机制：涂层的微纳复合结构有利于细胞的黏附、增殖，纳米棒结构对细胞的“钉扎”作用强，且有利于相关蛋白如a-SMA，CTGF，Col-I等的表达及细胞外胶原的分泌，从而植入体表面与软组织之间形成良好的生物整合；提出了多孔钛孔壁表面呈高结合强度、生物活性、长期高效抗菌的“纳米CuO/钛酸钠纳米纤维/掺Zn二氧化钛”复合涂层的结构优化构建方案，该涂层有望促进多孔钛内孔壁与真皮及皮下组织形成牢固结合，降低上皮移行、撕裂以及细菌感染引起的种植体失效。研究结果发表SCI期刊论文10篇，其中影响因子大于5的5篇；申请专利6项，其中授权5项（1项技术转让）；培养博士生1人（在读），硕士生6人(毕业4人，在读2人)。