PCL膜表面阿仑膦酸钠梯度构建及其诱导干细胞定域分化的研究

发布时间：2018-01-26 12:05

本文关键词： 组织工程梯度材料聚己内酯胺解骨髓间充质干细胞成骨分化　出处：《浙江大学》2012年硕士论文　论文类型：学位论文

【摘要】：组织工程在修复受损组织、器官中有广阔的应用前景。界面组织工程注重不同组织间连接部分(界面)的修复,突破了传统组织工程中针对单一组织进行修复的限制,蕴含很多新的科学问题。我们希望通过构建性质梯度渐变的生物材料,并诱导骨髓间充质干细胞(BMSCs)的定域分化以实现相邻组织界面的修复。胺解是聚酯材料表面改性的常见方法,可用于构建聚酯材料表面生物活性分子梯度以调控BMSCs的分化行为。但迄今有关胺解反应动力学及其对材料性质影响的研究尚不够深入系统,难以为梯度构建提供科学依据与技术支持。本文首先系统研究了反应条件对聚己内酯(PCL)膜胺解的影响,在此基础上梯度接枝了活性分子阿仑膦酸钠(Aln),成功诱导了大鼠BMSCs的定域分化,取得了以下有价值的成果： (1)探明了小分子二胺分子量等反应参数对胺解反应的影响；阐明了1,6-己二胺浓度及反应温度与反应速率的关系,以调控反应速率和膜表面-NH2的密度。利用注射法梯度胺解了PCL膜,并通过戊二醛偶联Aln,成功构建了Aln线性密度梯度。 (2)发现大鼠BMSCs可正常粘附于不同Aln密度的PCL-Aln膜表面并进行增殖。通过与表面受体Cx43结合,Aln可促进BMSCs的成骨分化,其效应与Aln密度大小正相关。梯度分布的Aln定域上调成骨相关蛋白碱性磷酸酶(ALP)、一型胶原(Col I)、成骨相关转录因子Runx2和骨钙素(OCN)的表达,显示其成功诱导了BMSCs的定域分化。
[Abstract]:Tissue engineering has a broad application prospect in repairing damaged tissues and organs. The interface tissue engineering focuses on the repair of the joint part (interface) between different tissues. It breaks through the limitation of single tissue repair in traditional tissue engineering and contains many new scientific problems. We hope to construct biomaterials with gradient gradient. Local differentiation of bone marrow mesenchymal stem cells (BMSCs) was induced to repair adjacent tissue interfaces. Aminolysis is a common method for surface modification of polyester materials. It can be used to construct the molecular gradient of surface biological activity of polyester materials to regulate the differentiation behavior of BMSCs. However, the studies on the kinetics of amination reaction and its influence on the properties of polyester materials have not been thoroughly and systematically studied up to now. It is difficult to provide scientific basis and technical support for gradient construction. Firstly, the effect of reaction conditions on the amination of PCL membrane was studied systematically. On this basis, the active molecule Alendronate sodium alendronate was gradely grafted, and the local differentiation of rat BMSCs was induced successfully, and the following valuable results were obtained. 1) the influence of the reaction parameters such as the molecular weight of small molecule diamine on the amination reaction was investigated. The relationship between the concentration and temperature of 1-hexane diamine and the reaction rate was elucidated to regulate the reaction rate and the density of -NH _ 2 on the surface of the membrane. The PCL membrane was prepared by injection of gradient amine. The linear density gradient of Aln was successfully constructed by glutaraldehyde coupling. (2) it was found that rat BMSCs could adhere to and proliferate on the surface of PCL-Aln membrane with different Aln densities and bind to the surface receptor Cx43. Aln can promote the osteogenic differentiation of BMSCs, and its effect is positively related to the density of Aln. The gradient distribution of Aln upregulated the osteoblast-associated protein alkaline phosphatase (ALP). The expression of osteoblast-associated transcription factors (Runx2) and osteocalcin (OCN) in collagen I showed that they could induce the local differentiation of BMSCs successfully.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08

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