瓣膜钙化是生物瓣衰败的主要原因，也是生物瓣研究的主要瓶颈；我们前期研究发现：利用纳米载体负载VEGF165对去细胞瓣进行内皮化以覆盖瓣膜钙化位点，虽能延缓瓣膜钙化，但瓣膜最终还是走向钙化；研究认为成骨分化关键基因Runx2的表达上调促使心脏瓣膜间质细胞向成骨细胞表型转化是心脏瓣膜钙化的重要机制；但纳米载体负载钙化相关基因Runx2靶向干预心脏瓣膜钙化的研究未见报道，其机制也不清楚；本项目拟采用siRNA技术，借助非病毒纳米载体PEG-PCL-PEI，对Runx2进行特异性靶向沉默；利用PEG-PCL-PEI-Runx2-siRNA纳米粒修饰的去细胞瓣和记忆合金网状支架构建可微创植入的抗钙化心脏瓣膜，并进行微创动物模型体内外抗钙化的研究；旨在探讨Runx2特异性靶向沉默促进心脏瓣膜体内外抗钙化的机制，为心脏瓣膜抗钙化研究提供新的思路。

Valve calcification is a major cause of bioprosthetic valve failure, also is the main obstacles of bioprosthetic valve research; Our previous study suggested that endothelialization on decellularized valve scaffolds by loading VEGF165 (vascular endothelial growth factor 165) with nano delivery system on the surface of the scaffold can delay valve calcification, but unfortunately they are intend to calcification ultimately,Other studies have shown that valvular interstitial cells into osteoblast-like phenotype play a vital role in calcification of valve, the result is up-regulated the expression of Runx2 which is a key gene for osteogenic differentiation, inducing valvular calcification.but targeted intervention of cardiac valvular calcification by delivering calcification related gene Runx2-siRNA with nano vector has not been reported and its mechanism is not very clear; the project intends to adopt siRNA (small interfering RNA,) technology, using non viral vector nano delivery system poly (ethylene glycol) -poly (-caprolactone) -poly (ethylene, imine, PEG-PCL-PEI), for the purpose of specific targeting Runx2 science;and construct minimally invasive implantable anti calcification heart valve with PEG-PCL-PEI-Runx2-siRNA nanoparticles modified Valve and shape memory alloy mesh stent.Then in vivo and vitro anti calcification research will carry out in the model of minimally invasive animal ; our research aim at exploring the mechanism of Runx2 targeting slience to promote heart valve anticalcification in vitro and in vivo , and provide a novel idea for the research of heart valve anti calcification .