种植体含锶纳米管涂层制备和骨结合能力与分子机制研究

Titanium dental implant has been widely used in clinic, but a series of issues still exist, such as early failure, infection and unavailability for osteoporotic condition. Faster and better osseointegration in both intact and osteoporotic conditions is the key to solve these issues. Recently, we have reported that titania nanotubes have intrinsic osteogenesis inducing ability. Considering that titania nanotubes actually serve as a good drug loading and delivering platform and the outstanding ability of strontium (Sr) to positively regulate bone turnover and promote implant osseointegration, we plan to develop Sr loading nanotubular coating on dental implant that can long-lastingly release Sr in a controlled mode, to abtain better osseointegration. In order to accomplish this, titania nanotubes will be treated by a hydrothermal process in Sr solution, and the nanotubular structure will be retained by optimizing the hydrothermal process and the Sr release rate will be tuned by related parameters. After fabrication, the surface properties of Sr loading nanotubes will be well characterized, including Sr loading amount and release rate. In vitro experiments will be conducted to observe the effect of the Sr loading nanotubes on bone mesenchymal stem cell functions especially osteogenic differentiation. Then the in vivo osseointegration of the Sr loading nanotubes will be observed in both intact and osteoporotic rats. And then the sample that generates the best osseointegration will be determined. Further, the influence of the two factors nanotubular cue and Sr in the Sr loading nanotubes on bone related signal pathways will be inspected to deeply understanding their biological effect and further guide their structure optimization. The Sr loading nanotubes, combining the dual effects of nanotubes and Sr, are very promising to generate long-lasting and strong in vitro osteogenesis inducing ability and good in vivo osseointegration.

牙科钛种植体广泛用于临床但仍存在一系列问题如早期失败、感染和骨质疏松禁忌症等，而如何在正常和骨质疏松条件下形成更快更好的骨结合是解决它们的关键。最近我们发现氧化钛纳米管有内源性成骨诱导能力,同时考虑到氧化钛纳米管的载药能力和锶对正常和骨质疏松个体正向调节骨代谢平衡和促进种植体骨结合的作用，本课题提出将氧化钛纳米管在锶溶液中水热处理，设法完整保留纳米管结构并通过相关参数调控锶的释放，构建可长期缓释锶的含锶纳米管种植体涂层以获得长期强效的骨结合能力。对其材料学特性包括锶的载入量和释放进行系统表征，体外观察其对骨髓间充质干细胞功能特别是成骨分化的影响，体内观察在正常和骨质疏松动物模型内的骨结合情况，从而筛选出骨结合能力最佳的结构。探讨含锶纳米管中锶和纳米管两因素对成骨相关信号通路的交互作用以更好地指导优化其结构。该含锶纳米管涂层将纳米管和锶二者的作用结合起来有望获得更好的种植体骨结合和临床功能。

如何在正常和骨质疏松条件下形成更快更好的骨结合是钛种植体需要解决的关键问题。本课题提出将氧化钛纳米管在锶溶液中水热处理，设法完整保留纳米管结构并通过相关参数调控锶的释放，构建可长期缓释锶的含锶纳米管种植体涂层以获得长期强效的骨结合能力。对其材料学特性包括锶的载入量和释放进行系统表征，体外观察其对骨髓间充质干细胞功能特别是成骨分化的影响，体内观察在正常和骨质疏松动物模型内的骨结合情况，从而筛选出骨结合能力最佳的结构。探讨含锶纳米管中锶和纳米管两因素对成骨相关信号通路的交互作用以更好地指导优化其结构。该含锶纳米管涂层将纳米管和锶二者的作用结合起来有望获得更好的种植体骨结合和临床功能。我们通过氧化钛纳米管水热处理的方法制备了不同管径的含锶纳米管种植体涂层。该涂层可以长期可控释放锶，无明显细胞毒性。锶的载入可以促进骨髓间充质干细胞的增殖，同时特定结构的含锶涂层可以促进骨髓间充质干细胞的成骨分化。通过动物模型，我们证明载锶纳米管涂层促进钛种植体在动物模型体内的骨结合。我们还将含锶纳米管涂层应用到3D打印的钛多孔骨植入材料表面，可有效促进成骨和骨长入材料内部。由此可见，载锶纳米管涂层有望成为新一代的种植体涂层应用于临床。