面向生物制造的梯度化水凝胶内细胞3D自组装机理的研究

项目名称： 面向生物制造的梯度化水凝胶内细胞3D自组装机理的研究

项目编号： No.51505127

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 机械、仪表工业

项目作者： 朱晓璐

作者单位： 河海大学

项目金额： 21万元

中文摘要： 利用细胞的自组织特性构建三维（3D）多细胞结构正成为生物制造和组织再生的一种重要途径并获得越来越多的关注。为进一步研究多细胞3D自组装机理，并使得细胞自组装过程以及细胞因子浓度梯度可控，本项目提出对内部结构特征梯度化（非均匀分布）凝胶块组合体材料中细胞3D自组装机理进行研究。首先，利用光致介电泳力对多个凝胶微块进行操控使其排列成组合体，建立相应的体外试验模型进而对其内部的细胞进行3D自组装试验；其次，基于反应-扩散机制建立描述上述体外试验模型中细胞3D自组装过程的数学模型；然后，根据此体外试验模型及试验结果确定数学模型中激活子、阻滞子及细胞的扩散系数矩阵、反应项中的表达式等；最后，通过仿真计算研究数学模型中各物理变量对3D多细胞结构的影响规律，并结合对应的试验结果归纳出调控细胞自组装过程及形成各类3D多细胞结构的方法。

中文关键词： 微操控；生物制造；梯度化凝胶；三维细胞自组装

英文摘要： The use of cellular self-organization for constructing three-dimensional (3D) multicellular structures is receiving increased attention for bio-manufacturing and regenerating injured tissue. In order to further study the mechanism of 3D self-assembly of cells and find a reliable way to control this self-organization process and regulate the spatial gradients of the concentrations of cytokines, this project proposes to study the mechanism of 3D cellular self-assembling inside structurally graded hydrogel. First, the structurally graded hydrogel is constructed by manipulating multiple hydrogel cuboids using optically induced dielectrophoretic force, and thus the in vitro model is established for the experimental study on self-assembly of cells inside the hydrogel cuboid combination; Second, a mathematical model based on a Turing-type reaction-diffusion (R-D) framework is planned to be built to explain the experimental results. Third, the diffusion coefficient matrixes of activator, inhibitor and cells as well as the expression of reaction terms are expected to be determined according to the configuration of the in vitro model and experimental results of 3D structure morphology. Finally, the impact of the physical variables in the complete mathematical model on the final 3D cellular structures should be studied through simulations, which could be verified by corresponding experiments. Consequently, the methodology for constructing diverse 3D multicellular architectures could be generalized.

英文关键词： Micro-manipulation;Bio-manufacturing;Structurally graded hydrogel ;3D self-assembly of cells