心血管金属材料表面诱导内皮原位修复的微环境构建及动物半体内/体内研究与信号通路探索

项目名称： 心血管金属材料表面诱导内皮原位修复的微环境构建及动物半体内/体内研究与信号通路探索

项目编号： No.31470921

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 陈俊英

作者单位： 西南交通大学

项目金额： 90万元

中文摘要： 心血管金属材料被广泛应用, 但其生物相容性远未满足要求。诱导内皮原位修复是改善生物相容性的最有效途径。然而，体内潜能干细胞动员、迁移、靶位归巢及定向分化等都取决于植入材料的表面环境。因此，在表面构建功能微环境是诱导内皮原位修复的突破口。本项目拟将趋化因子（SDF-1/VEGF）和细胞响应关键蛋白（Ln/多肽）引入Ti表面，构建具有内皮诱导与原位修复功能的微环境。通过控制载入量、活性、稳定性等实现原位内皮诱导。借助体外及模拟流场实验探索内皮诱导过程中生物分子（因子）/细胞之间的主要信号通路。通过不同种类（兔和狗）、不同埋置时间（数小时至1年）的动物体内与半体内实验评价微环境诱导内皮及原位修复情况。用酶标、ELISA、PCR、放免、WB等手段进行微环境诱导内皮修复、再生及功能的定性/量检测，阐明微环境诱导内皮及原位修复的主要信号通路与分子机制。本项目将推进心血管材料表面功能微环境研究的进展。

中文关键词： 趋化因子；细胞响应蛋白；原位诱导内皮；动物实验；信号通路

英文摘要： Cardiovascular metal biomaterials have been extensively used in clinical treatment of cardiovascular diseases.However, the biocompatibility of devices is remaining far from perfect. Induced in-situ endothelium regeneration is now considered the most effective approach to improve the biocompatibility of cardiovascular materials. Due to the key role of materials surface properties contribute to the in vivo mobilization, targeted migration, homing and directed differentiation of pluripotent stem cell, construct a biomimetic microenvironment on materials surface using biomacromolecules and functional factors is now suggested to be a breakthrough in induced endothelium regeneration research. This project intends to integrate chemotactic factors (SDF-1/VEGF) and key proteins (Ln/peptide) in cellular response onto titanium surface to construct a biomimetic microenvironment with the function of induced endothelialization and in-situ regeneration. The property of induced endothelialization will be achieved by controlling the loading quantity and bioactivity of biofunctional molecules. The major signaling pathways between biomacromolecules (factors) and cells during the process of induced endothelialization will be investigated by in vitro and dynamic simulation experiment. In vivo and ex vivo study will be performed in various animal models (rabbit and dog) with different embedding time (hours to one year) to evaluate the effect of the microenvironment on endothelium regeneration. Systematic characterization, as well as qualitative and quantitative determination will be carried out by ELISA, PCR,WB，radioimmunoassay, and tissue slice et al to expound the major signaling pathways and molecular mechanisms during the process of microenvironment induced endothelialization and in-situ regeneration. This project will promote the development of cardiovascular materials surface bio-functionalization research.

英文关键词： chemokines;cell response key protein;in-situ inducing;in vivo investigation;signaling pathway