具有负载核酸复合体及表面抗菌功能的骨组织工程支架的构建及其作用机制研究

大于临界尺寸的骨缺损的修复及其治疗过程中可能发生的感染问题，是目前骨科临床上的常见问题。针对这一问题，本项目提出构建具有负载核酸复合体及表面抗菌功能的骨组织工程支架，用于感染型骨缺损的治疗。通过多氨基、多环氧基小分子化合物的开环反应，合成系列超支化阳离子基因载体，并对其进行后修饰，使其对成骨相关细胞具有低毒高效的作用。将合成的基因载体与携带促成骨基因的核酸复合，制备骨组织工程支架材料负载核酸复合体，以增强骨修复的效果。对获得的负载核酸复合体的骨组织工程支架进行表面抗菌功能化，使其具备抗感染的能力。对所构建的具有负载核酸复合体及表面抗菌功能的骨修复材料进行全面的理化结构分析和生物学性能评价，探索其构效关系与作用机制，并对其体内抗感染、促修复性能进行验证。通过本项目的研究，有望获得具有良好促骨修复和抗菌性能的骨组织工程支架，并为将来新型材料的研发提供理论依据。

The therapy methods of large bone defects and infection are the common problems in orthopedics. To solve these problems, this project proposes to fabricate functionalized bone tissue engineering scaffolds with nucleic acid complex-loading and surface antibacterial properties for the therapy of infectious bone defects. To realize the high transfection efficiency and low toxicity on osteogenesis-related cells, a series of novel polycationic gene carriers will be synthesized by the ring-opening reaction of small molecules with multiple amino groups or epoxy groups, followed by modification by bioactive molecules. The gene carriers will condense the nucleic acids with osteogenesis-promoting genes to form nanocomplexes. The nanocomplexes will be loaded by biodegradable bone tissue engineering scaffolds to achieve high performance on bone reparation. To resist the infection during the therapy process, the surfaces of nanocomplex-loaded scaffolds will be functionalized with antibacterial polymer. The physical, chemical and biological properties will be universally characterized, and the relationship between their structures and performances will be illustrated. Moreover, their in vivo bone regeneration and anti-infection efficiencies will be confirmed by animal experiments. By this project, a series of novel bone tissue engineering scaffolds with high performance on bone regeneration and antibacterial, and the theory basis will be provided to develop new bone tissue engineering scaffolds in future.