Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures
Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures
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DOI：
10.1016/j.biomaterials.2006.05.044
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发表时间：
2006-10-01
期刊：
影响因子：
14
通讯作者：
Langer, Robert
中科院分区：
文献类型：
--
作者：
Fukuda, Junji;Khademhosseini, Ali;Langer, Robert
生物工程方法，如多种细胞类型的共培养，旨在模拟生理微环境，可能有利于优化细胞功能和体外工程组织。本研究描述了一种在微凝胶上单独或在共培养条件下制备球形微阵列的新方法。合成了光交联壳聚糖，并利用微模塑工艺制备了水凝胶微结构。壳聚糖表面最初是细胞排斥的，但随着时间的推移，细胞粘附性越来越强。通过利用壳聚糖水凝胶的这一独特性质，有可能产生球体和支持细胞的图案化共培养。在该方案中，细胞首先在微孔的低剪切应力区内微排列。接种于这些孔中的人肝母细胞瘤细胞Hep G2在培养期间形成大小和形状可控的球形细胞，并稳定地分泌白蛋白。壳聚糖表面细胞黏附特性的改变促进了第二种细胞NIH-3T3成纤维细胞的黏附和生长，从而使肝细胞球体和成纤维细胞单层共培养成为可能。这种共培养系统可能成为研究异型细胞-细胞相互作用、药物筛选和开发可植入生物人工器官的有用平台。(C)2006爱思唯尔有限公司。保留所有权利。
Bioengineering approaches, such as co-cultures of multiple cell types, that aim to mimic the physiological microenvironment may be beneficial for optimizing cell function and for engineering tissues in vitro. This study describes a novel method for preparing a spheroid microarray on microfabricated hydrogels, alone or in co-cultures. Photocrosslinkable chitosan was synthesized and utilized for fabricating hydrogel microstructures through a micromolding process. The chitosan surface was initially cell repellent but became increasingly cell adhesive over time. By using this unique property of chitosan hydrogels, it was possible to generate patterned co-cultures of spheroids and support cells. In this scheme, cells were initially microarrayed within low shear stress regions of microwells. Human hepatoblastoma cells, Hep G2, seeded in these wells formed spheroids with controlled sizes and shapes and stably secreted albumin during the culture period. The change of cell adhesive properties in the chitosan surface facilitated the adhesion and growth of a second cell type, NIH-3T3 fibroblast, and therefore enabled co-cultures of hepatocyte spheroids and fibroblast monolayers. This co-culture system could be a useful platform for studying heterotypic cell-cell interactions, for drug screening, and for developing implantable bioartificial organs. (c) 2006 Elsevier Ltd. All rights reserved.