骨诱导性钙磷陶瓷与宿主局部微环境间交互应答机制及骨再生效应的研究

项目名称： 骨诱导性钙磷陶瓷与宿主局部微环境间交互应答机制及骨再生效应的研究

项目编号： No.81470720

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： 李继华

作者单位： 四川大学

项目金额： 73万元

中文摘要： 骨诱导性多孔钙磷陶瓷是一类具有生物活性的仿生骨替代材料，植入后以宿主机体作为生物反应器构建组织工程化骨，用于修复骨缺损取得了较好的治疗效果。然而，陶瓷材料植入后在接触界面局部微环境与宿主发生交互应答并诱发骨再生的调控机制尚未阐明，还存在成骨不足，骨整合不良，形态难于精确控制等问题限制了它的临床应用。本项目在自主研发的骨诱导性钙磷陶瓷基础上，拟通过快速原型技术制备出与宿主骨外形、结构和力学性能相匹配的多孔支架，植入动物体内整复极限骨缺损，并运用基因组学和蛋白组学等技术探索调控MSCs,在陶瓷-宿主骨界面上增殖、骨向分化等应答的关键信号通路及作用环节，并运用流式细胞、基因抑制消减、RNAi、Westen blot等技术筛选出关键信号调控因子，并探索靶向应用所选因子的缓控载药方式,作用于细胞或支架局部微环境,评价其促进骨再生及骨整合的实际效果，实现在体内构建组织工程骨领域中关键核心技术的突破。

中文关键词： 骨再生；组织工程骨；骨髓间充质干细胞；信号通路

英文摘要： Osteoinductive porous calcium phosphate ceramics are regarded as a novel class of biomimetic bone substitute with biological activity. After implantation the host organism is used as bioreactor to construct tissue-engineered bone shows a relatively good therapeutic effect in the reconstruction of bone defect. However, the mechanism of interactive response at the implant/bone interface of the local microenvironment and induction bone tissue regeneration is still unclear. And its clinical application is limited by defects including osteogenesis inadequate , poor osseointegration , difficulty in shape controling. Our project is about to implant porous scaffolds, fabricated by rapid prototyping technology, which is matching the host bone shape, structure and mechanical properties, in experiment animals to repair the extreme bone defect on the basis a self-developed calcium phosphate ceramic. By means of some techniques，such as genome science and proteomics techniques, we could explore the pivotal signaling pathway and action segment regulate the proliferation and differentiation of MSCs in the interface of bone-ceramic. Besides, the key regulation factors would be selected by flow cytometry, gene suppression, gene subtraction, RNAi, Westen blot and so on. And the role of the drug-loading pattern targeting the selected factors in local microenvironment would be studied. To evaluate the promoting effect of bone regeneration and bone integration and achieve a breakthrough in the field of core technologies of construction of tissue engineered bone in vivo.

英文关键词： bone regeneration;tissue engineering bone;MSCs;signaling pathway