骨修复生物活性材料与宿主微环境的相互作用

Interaction between materials and host microenvironment in vivo which provides place for bone regeneration can directly affect healing rate and quality of new bone formation. Therefore, with taking the post-implantation time of bioactive materials for bone repair as principle line and catching the key points which determine healing rate and quality of regenerated bone tissue, we will thoroughly study on the dynamic formation rule of post-implantation host microenvironment from multi-layers of tissue, cell and molecule by variety of advanced technology and new methods such as bimolecular fluorescence complementation (BiFC), protein microarray, Shanghai synchrotron radiation for in-situ microscopic imaging, in vivo imaging technology in small animal, blood vessel microscopic imaging, positron emission tomography (PET) and so on. In this study, materials regulation upon behavior of related osteoblastic cells, key signal/ transcription factor and signal path in host microenvironment will be identified. Meanwhile rule and mechanism of bone tissue regeneration and vascularization as well as materials degradation will be investigated. Eventually, basic theoretical framework of interaction between bioactive materials and host microenvironment might be integrated with above mentioned effect mechanism relating composition and structure of material and some growth factors. Our research findings will reveal interaction between material and host through core process of bone tissue regeneration and provide theoretical basis for research on novel high quality bone repair material as well as its clinical application. Furthermore, it’s expected this study may enrich the basic theory of bone repair mediated by materials.

体内宿主微环境是骨组织再生的场所，材料与宿主微环境之间的相互作用直接影响骨组织形成的速度和质量。为此，本课题将以骨修复生物活性材料植入后的时间为主线，抓住决定骨组织再生速度和质量的关键环节，借助双分子荧光互补技术、蛋白微阵列、上海同步辐射光源原位显微影像、小动物活体成像、血管显微及小动物正电子发射断层显像等先进技术与新方法，从组织、细胞和分子水平多层面深入研究材料植入后宿主微环境的动态形成规律；明确在宿主微环境中，材料对成骨相关细胞行为的调控以及关键信号/转录因子和信号通道的作用；研究骨组织再生和血管形成以及材料降解的规律及机制；阐明材料的组成、结构、生长因子对上述过程的影响规律，最终集成出生物活性材料与宿主微环境相互作用的基本理论框架。研究成果将从骨组织再生的核心过程揭示材料与宿主的相互作用，为新型高质量骨修复材料的研制与临床应用提供理论依据，并丰富材料介导骨修复的基础理论。

材料植入后与宿主体内环境共同组成了新的微环境，对组织再生起了重要作用。本研究围绕活性骨修复材料与宿主微环境之间的相互作用，以材料植入后的时间为主线，探索了材料的离子组成（镁离子、硅离子）、支架的微观孔道结构和特定的分子量及官能团（磺化多糖）对组织再生相关细胞行为及其所介导的骨修复中序列事件的影响规律。研究发现，无机钙磷材料中引入低浓度的镁离子可降低巨噬细胞的炎性响应，并促进细胞粘附，同时镁离子激发产生的免疫微环境可上调了成骨和成血管基因的表达，对骨组织修复产生积极作用；具有多级结构的支架有利于生长因子的活性维持，不同的拓扑结构也影响细胞的粘附和分化行为；发现磺化多糖的促血管化作用以及和VEGF生长因子的协同作用，基于磺化壳聚糖的活性材料在大段骨修复的动物实验中显示出良好的修复效果。本研究提出了“材料生物学”的学术新思想，借助材料的生物学效应，激发和调控微环境中的细胞行为，促进骨组织再生的观点，为构建新型组织再生生物材料提供了新思路和实验依据。