微纳米矿化丝素/硫酸钙双缓释系统的构建及其促进感染性骨缺损修复的机理研究

Nowadays, numerous studies have been proceed on the reconstruction of infectious bone defect for the local therapy. However, some questions and mechanism such as, the sustained release of drug, similar mechanical strength to natural bone, matching degradation rate, as well as bioactivity, are still difficult to treat and brings challenges to researchers. The present project intends to construct biomimetic micro/nano- mineralized silk/calcium sulfate drug delivery system on the basis of previous work. The project proposed to study the way of binding mode as well as the mechanism of chemical bond between molecules during the combination of drug, silk and calcium sulfate, and its effect and mechanism on delivery system controlling the drug release and the degradation of silk/ calcium sulfate scaffold. The synergistic effect of structure and organic/inorganic composition of composite on bone repair in delivery system will be investigated. Furthermore, the mechanism of nano-silk improving mechanical, degradable properties and osteogenic differentiation of bone marrow mesenchymal stem cells will be clarified. At last, animal experimental mode will verified the antibacterial and osteogenic effect. The present study is helpful to support the theoretical and experimental evidence for infectious bone defect.

为实现对感染性骨缺损的修复，抑制感染同时骨缺损再生的问题已经成为骨科临床局部治疗中的研究热点。但目前对载药支架中药物如何实现缓慢释放，同时支架材料如何在力学、降解性、生物活性等方面与人体骨匹配并成骨，仍没有有效解决并阐明机理。本项目在前期研究的基础上拟构建一种仿生的微纳米矿化丝素/硫酸钙双缓释系统。提出研究该复合载药系统中药物（万古霉素）与丝素及硫酸钙复合过程中的分子间结合方式和化学键合，并研究其与复合载药系统的药物释放行为及矿化丝素/硫酸钙支架材料降解的关系与机理；同时探索复合载药系统中有机/无机组分及结构对骨愈合促进的协同作用，并就纳米丝素对改善硫酸钙力学、降解性能、成骨分化作用及相关机理进行阐明。最终通过动物实验模型加以验证抗感染和成骨效果。该项目的研究将对有效解决感染性骨缺损的临床难题提供理论和实验依据。

为实现对感染性骨缺损的修复，抑制感染同时骨缺损再生的问题已经成为骨科临床局部治疗中的研究热点。但目前对载药支架中药物如何实现缓慢释放，同时支架材料如何在力学、降解性、生物活性等方面与人体骨匹配并成骨，仍没有有效解决并阐明机理。本项目在前期研究的基础上构建了一种仿生的微纳米丝素/硫酸钙缓释系统并研究药物释放及抗菌行为；在硫酸钙中复合丝素微球后，随着微球丝素浓度增加，复合人工骨材料药物释放速率逐渐减小。同时研究探索纳米丝素纤维对改善硫酸钙力学、降解性能、成骨作用及相关机理；丝素纳米纤维作为固化液不仅能够有效的降低复合材料的降解率、抑制药物的突释，而且显著的提高了复合材料的强度、韧性。复合纳米丝素纤维的材料，更有利于细胞的黏附和增殖；最终通过动物实验模型加以验证了抗感染和成骨效果。该项目的研究将对有效解决感染性骨缺损的临床难题提供理论和实验依据。