面向组织工程的多细胞结构三维自组装成形方法的研究进展

多细胞结构是由细胞群体构成的有机体,其体外构建对于组织工程和再生医学的发展具有重要的基础意义。利用细胞自身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,并受到越来越多的关注。对三维多细胞结构的自组装式构建与调控的相关基础研究及关键技术进行了综述及分析,主要涉及凝胶内3D细胞培养、多细胞结构可控形成,及其与图灵反应-扩散机制的联系等方面的研究工作。为进一步研究多细胞3D自组装机理,使得该自组装过程可控,且满足同时调控外部施加和细胞自身分泌的作用因子的浓度梯度分布的需求,提出对内部结构特征梯度化的3D凝胶体内细胞3D自组装模型进行研究,以推进三维多细胞结构及组织前体形成的理性调控技术。

Research progress of the three-dimensional(3D) multicellular structure formation via self-assembly of cells toward tissue engineering

Multicellular structures are organisms consisting of cell populations, and constructing multicellular structure is of great importance for the development of tissue engineering and regenerative medicine. The use of self-organization processes in three-dimensional (3D) culture is receiving increased attention for bio-manufacturing and regenerating injured tissue. This review covers the research work on the fundamental and key techniques regarding 3D cellular self-assembly. It includes the 3D culture of cells inside bio- compatible hydrogels, controllable formation of 3D multicellular structure, and the associated Turing reaction-diffusion mechanism. In order to further study the mechanism of 3D self-assembly of cells and find a reliable way to regulate this self-organization in 3D extracellular matrix with spatial gradients of the concentrations of exogenous and cell-secreted factors, this review at last proposes to study the 3D models of cellular self-assembling inside structurally graded hydrogel, so that the development of rational regulation technology for 3D multicellular structure and tissue bud could be facilitated.