骨修复植入体表面力-电响应微环境的构建及其骨整合机制研究

骨修复植入体是临床用量最多的生物材料之一，但存在难以与骨组织实现直接骨性结合、成骨速度慢等问题。依据人体骨具有力-电响应特性、外加电信号刺激可促进骨细胞增殖分化、血管生成和神经生长以及临床施加弱电信号可刺激骨的修复重建等研究成果，基于材料表面骨整合是包含骨组织再生、血管生成和神经生长对骨重建有调控作用的复杂生物学过程，申请人提出“材料的持续力-电响应微环境可促进骨整合”的科学假想，通过表面功能化构建技术制备具有力-电响应微环境特性的钛植入体用于骨组织、神经和血管一体化修复。研究材料成型工艺对力-电响应微环境的影响规律；建立材料表面力-电响应微环境/细胞作用模型，探究其微环境的力-电信号对成骨系细胞、血管内皮细胞和神经细胞增殖与分化的影响机制，及其对细胞内物质和细胞内生化反应的作用机理；通过动物实验阐明骨修复植入体表面力-电响应微环境促进骨整合机制，为临床发展新型骨植入材料提供新思路。

Bone repair implants are one of the most consumed biomaterials in clinical orthopaedics. However, the application of this material still has a series of limitations, for example, it is difficult for the biomedical titanium to achieve direct bone bonding and fast osteogenesis. Based on previous research results that human natural bone has mechano-electric response characteristics, external electrical signal stimulation can promote osteoblast proliferation, angiogenesis and nerve growth, and weak electrical signal stimulation can stimulate bone repair and reconstruction in clinical practice, as well as the osseointegration of implant materials is a complex biological process that includes bone tissue regeneration, neovascularization and nerve regulation of bone remodeling, the applicant puts forward the scientific hypothesis that "Sustainable Mechano-Electric Response Microenvironment of Materials Promote Osseointegration". For the first time, titanium implants with mechano-electric response microenvironment characteristics are constructed via surface functionalization technology to realize integrated repair of bone tissue, nerves and blood vessels. The influence role of materials construction process on its mechano-electric response will be carefully studied. The interaction model between the mechano-electric response microenvironment and the cells will be developed to study the working mechanism of the mechano-electric responsive cues on the proliferation and differentiation of osteoblast, vascular endothelial cell cells, and nerve cells, in order to uncover the molecular mechanism of the impact of mechano-electric responsive cues on the intracellular physical and chemical reaction. Moreover, animal implantation experiment will be carried out to illuminate the mechanism of osteointegration enhancement under sustainable mechano-electric response microenvironment. This research will provide a new thought and avenue for novel bone implant materials development.