氧化铈纳米颗粒表面重塑诱导组织工程骨血管化及其作用机制研究

项目名称： 氧化铈纳米颗粒表面重塑诱导组织工程骨血管化及其作用机制研究

项目编号： No.81471782

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： 杨小超

作者单位： 中国人民解放军第三军医大学

项目金额： 72万元

中文摘要： 因再生血管分布密度和浸润深度不够而导致组织坏死或纤维化是组织工程骨（TEB）面临的严峻挑战，血管内皮细胞是TEB血管再生的核心细胞，其增殖和迁移对TEB血管再生有关键影响。我们前期发现，通过改变晶体结构、包覆聚合物和嫁接功能基团等手段对氧化铈纳米颗粒（CNPs）进行表面重塑后，该纳米颗粒可使血管内皮细胞的增殖及迁移速度提高70%和160%，这提示表面重塑后的CNPs是潜在的血管再生诱导剂。本项目拟探索CNPs表面重塑及其诱导TEB体内原位血管再生的可行性，内容包括：构建CNPs表面重塑体系，分析表面重塑对其生化活性的影响；探索CNPs表面重塑对血管内皮细胞生长行为的影响，阐明其具体作用机制；建立表面重塑后的CNPs同TEB支架复合的方法，体外优化其骨和血管再生诱导性能；制定基于CNPs的TEB体内原位血管再生诱导策略，并在体内进行实验验证。项目的成功实施可为TEB血管化研究提供一种新思路。

中文关键词： 组织工程骨；血管化；血管再生；氧化铈；纳米颗粒

英文摘要： The practical application of tissue engineering bone (TEB) is challenged by tissue necrosis and fibrosis due to the insufficient blood vessel distribution and diffusion. Vascular endothelial cell is the core cell for TEB vascularization. The proliferation and migration of vascular endothelial cell have significant effect on the formation of new blood vessels. Recently, we found that surface remodeling of ceria nanoparticles (CNPs) through changing the nanoparticle crystal structure, coating the nanoparticle with polymer and conjugating the nanoparticle with functional groups could significantly promote the growth of vascular endothelial cell. Our preliminary data indicated that the proliferation rate and migration area of vascular endothelial cells cultured with surface remodeled CNPs were 70% and 160% higher than that of vascular endothelial cells cultured without CNPs. These results imply that the surface remodeled CNP is potential reagent for angiogenesis. In the proposed project, we will study on the feasibility of using surface remodeled CNPs as induction agent for TEB vascularization. Firstly, the surface remodeling system for CNPs will be intensively studied. The biochemical activities variation of CNPs caused by the surface remodeling will be discussed. Secondly, the mechanism for the improvement of vascular endothelial cell growth induced by surface remodeled CNPs will be clarified. Thirdly, the methods of incorporating the surface remodeled CNPs into our previous reported TEB scaffold will be explored. The feasibility of the as prepared scaffold for bone and blood vessel regeneration will be evaluated and optimized in vitro. Fourthly, the angiogenesis induction strategies based on the surface remodeled CNPs will be studied and their feasiblity of blood vessel formation will be evaluated in vivo. The proposed project is aimed at exploring a new strategy for TEB vascularization.

英文关键词： Tissue Engineering Bone;Vascularization;Angiogenesis;Cerium Oxide;Nanoparticle