基于纳米结构的物理性niche调控MSC软骨向分化及促进大块骨软骨缺损再生研究

项目名称： 基于纳米结构的物理性niche调控MSC软骨向分化及促进大块骨软骨缺损再生研究

项目编号： No.81201395

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 蔡友治

作者单位： 浙江大学

项目金额： 24万元

中文摘要： 临床上，软骨塌陷和软骨下骨支撑不足是大块骨软骨缺损修复术后的常见问题。目前，有关骨软骨愈合机制尚不明确，因此临床上尚缺乏理想的生物支架用于组织工程骨软骨的构建。最新研究表明基质微环境可以通过整合素介导的力学转导通路影响干细胞分化。本研究假说：基于纳米结构的物理性niche可以定向调控MSCs分化，并通过微环境中整合素介导的力学转导信号通路影响软骨愈合。该研究拟利用前期成功建立的纳米纤维三维支架结构，模拟并控制基质微环境的不同变量，研究影响MSC软骨分化的主要拓扑结构，并明确调控机理，最后通过在体内原位骨软骨修复实验，评估组织工程化骨软骨支架的可行性和功效性。该研究将为调控MSCs向软骨分化提供全新的思路，并为利用干细胞和生物材料修复大块骨软骨缺损提供新的理论依据和新技术手段。

中文关键词： 软骨干/祖细胞；微环境；软骨源性祖细胞；软骨修复；组织工程

英文摘要： The clinical challenges relating to large osteochondral lesion repair are cartilage collapse and inferior mechanical properties in the subchondral bone layer, usually due to the failure of cartilage-bone healing. The basic biology of osteochondral healing remains incompletely understood. So it's necessary to design effective tissue-engineered scaffold for osteochondral regeneration. Recently some studies showed that matrix micro-environment could directly affect stem cell differentiation by integrin-mediated mechanotransduction pathway. So it's hypothesized that scaffold niche based on nano-structure could regulate the MSCs chondrogenesis by providing integrin-mediated molecular signal pathways and improve healing response in cartilage defect. In the current study main factors of matrix micro-environment affect MSCs differentiation will be produced based on 3-D nanofibrous structure. Then pathway how molecule signals affect MSC differentiation will be investigated. Finally the osteochondral scaffold on where MSCs are planted will be used to repair large osteochondral defect in vivo with the aim of developing an efficient tissue-engineered scaffold. This study is supposed to produce original experimental data and provide a new way to regulate MSC differentiation. With stem cell differentiation and tissue engineer

英文关键词： Cartilage stem/progenitor cells；microenvironment；chondrocyte derived progenitor cells；cartilage repair；tissue engineering