超顺磁性组织工程支架与外源磁场协同促进原位成骨的效应及机理研究

项目名称： 超顺磁性组织工程支架与外源磁场协同促进原位成骨的效应及机理研究

项目编号： No.81471793

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 许海燕

作者单位： 中国医学科学院基础医学研究所

项目金额： 73万元

中文摘要： 骨缺损处支架中的成骨细胞缺少持续和适度的力学刺激是导致其体内诱导成骨速度较慢和大块骨缺损难以修复的一个重要原因，如何使支架自身具有对细胞的力学刺激功能是加快新骨形成的关键问题。本项目拟构建含氧化铁磁性纳米颗粒的复合材料支架，利用超顺磁性纳米颗粒在外源磁场中，其磁矩由无序向与磁场同向转变的特性，使支架各处产生微振动和微形变，将磁场作用转化为支架对细胞的牵拉或者扭曲力。在静态或者交变磁场下，在多种细胞和动物骨缺损模型上，研究（1）支架的化学组成、微观结构、以及外源性磁场的强度和交变频率等因素与支架超顺磁响应能力之间的关系；（2）支架的超顺磁响应对成骨细胞表面的力传导分子（整合素）、细胞骨架结合蛋白及整合素相关信号通路的活化作用；（3）支架对成骨过程的促进作用；（4）支架环境中巨噬细胞功能的转变规律。阐明超顺磁性支架与外源性磁场促进骨组织再生的协同效应机制，建立支架引导成骨的新方法。

中文关键词： 纳米复合材料；超顺磁性；骨再生材料；组织工程；生物相容性

英文摘要： Large bone defects are a great challenge to reconstructive orthopaedic surgery, because the bone repair resulted from the conventional scaffold-induced bone regeneration in vivo is too slow to meet clinical demands. We consider that osteoblasts growing in the scaffolds implanted in defects are lack of constant and proper mechnical stimulation, which is one of the main reasons that lead to repair failures. Hence, it is crucial to make the scaffolds themselves have functions of giving cells mechanical stimulations. In this project, we will fabricate nanostructured composites with the integration of iron oxide magnetic nanoparticles. We hypothesized that the composite scaffolds generate small local vibration or deformation in response to extra applied magnetic fields due to their superparamagnetic properties. The small deformation and vibration apply stretch or twist force on cells growing in the scaffolds, which enhance scaffold-induced osteogenesis and lead rapid bone repair. We will investigate (1)the relationships between the scaffold chemistry, miscrostructures, strength and alternative frequency of extra magnetic fields and the superparamagnetic response behaviours, (2) interactions of scaffolds to the activation of mechanotransductive integrins, cytoskeletal linker proteins, integrin-associated signal cascades. (3) effects of scaffolds on the osteogenesis, and (4)interactions of the scaffolds to recruited macrophage cells (phenotypes and functions).Take above, to demonstrate mechanisms of the synergistic effect of superparamagentic scaffolds and magnetic fields and establish a new solution for scaffold-induced bone regeneration.

英文关键词： nanostructured composite;superparamagnetic;materials for bone regeneration;tissue engineering;biocompatibility