仿生纳米结构在钛种植体表面的抗菌作用与机理研究

Titanium dental implants are currently considered as a preferred strategy to restore missing teeth or dentition. Nevertheless, most methods of titanium surface modification improve the proliferation of osteoblasts as well as attachment and colonization of bacteria. These pathogenic bacteria might cause peri-implantitis, which leads to non-reversible bone loss and is the main reason for the failure of implantation. Thus, prevention is better than cure. Based on my preliminary study, illustrating the hydrophobicity, self-cleaning and antibacterial properties of gecko skin and its biomimetic replicas, the aim of this project is to fabricate the biomimetic nano-structures on the surface of titanium slices and titanium dental implants, by means of Micro-electromechanical Systems (MEMS) and etching, etc.. Subsequently, we will evaluate the antibacterial effect and bone formation ability in vitro, and the ability of preventing peri-implantitis and osseointegration on the screw-shaped dental implant in the Beagle dog model in vivo. Compared to coatings, the anti-bacterial effect of the nanostructure should be much more stable and long-lasting. In addition, there is no toxicity or side effect. All of these make it greatly promising to be applied in the dental clinic.

目前，钛种植体已成为修复牙列缺损或缺失的重要手段。然而，多种钛金属表面改性的方法促进成骨细胞生长的同时，也促进了细菌附着和聚集。由致病菌引起的种植体周围炎，导致不可逆的骨缺损，是种植失败的主要原因。为了防患于未然，本项目基于申请人前期研究阐明的壁虎皮及其仿生复制树脂表面的超疏水性、自清洁性和纳米结构的杀菌性，旨在进一步通过微电子机械系统和刻蚀等技术，将此仿生纳米结构形态，直接制备在钛片及钛种植体表面；并通过体外实验和Beagle犬体内实验，验证其有效抗菌、预防种植体周围炎的作用及骨形成性能。相比涂层，本项目中制备的纳米结构抗菌作用更稳定持久。此外，不存在毒副作用，具有极佳的临床应用前景。

基于自然界天然抗菌结构的口腔种植体表面改性是独辟蹊径的仿生医疗器械功能化策略。本项目基于申请人前期研究阐明的壁虎皮抗菌结构，在口腔种植体常用材料钛金属表面制备了仿生壁虎皮表面的纳米结构，并通过体外实验，验证了其有效抗菌及骨形成性能。主要取得成果包括：（1）通过微电子机械系统和刻蚀等技术，进行了纳米突刺钛表面结构构建。（2）选用2种常见的种植体周围炎致病菌：牙龈卟啉单胞菌和具核梭杆菌为模型细菌，对钛表面纳米结构进行了体外广谱抗菌性初探。（3）利用大鼠成骨细胞与人源骨髓间充质干细胞为模型细胞，对钛表面纳米结构进行了体外骨组织细胞生物相容性初探。（4）利用新型仿生螺旋聚异腈水凝胶（PIC），进行了钛种植体-口腔组织复合模型的构建初试。本项目将为仿生壁虎皮纳米抗菌钛种植体的未来临床应用打下坚实理论基础。