A photolabile hydrogel for guided three-dimensional cell growth and migration
A photolabile hydrogel for guided three-dimensional cell growth and migration
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DOI：
10.1038/nmat1092
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发表时间：
2004-04-01
期刊：
影响因子：
41.2
通讯作者：
Shoichet, MS
中科院分区：
文献类型：
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作者：
Luo, Y;Shoichet, MS
组织工程旨在通过在支持细胞浸润和组织组织化的三维（3D）生物材料支架上递送信号分子和细胞来替换、修复或再生组织/器官功能（1，2）。为了控制细胞行为并最终诱导表面上的结构和功能组织形成，平面基底已经用模拟空间线索的粘附信号图案化以引导细胞附着和功能（3-5）。本研究的目的是在3D水凝胶基质中创建生物化学通道，用于引导轴突生长。用含有巯基保护基的半胱氨酸化合物修饰的琼脂糖水凝胶提供了可以用生化线索图案化的光不稳定基底。在这种透明的水凝胶中，我们使用聚焦激光将粘附性纤连蛋白肽片段，甘氨酸精氨酸-甘氨酸-天冬氨酸-丝氨酸（GRGDS）固定在基质的选定体积中。我们在体外验证了GRGDS寡肽修饰的通道对3D细胞迁移和神经突生长的引导作用。这种用于将生物分子固定在3D基质中的方法通常可以应用于任何光学透明的水凝胶，为构建具有用于组织工程应用的程序化空间特征的支架提供了解决方案。
Tissue engineering aims to replace, repair or regenerate tissue/organ function, by delivering signalling molecules and cells on a three-dimensional (3D) biomaterials scaffold that supports cell infiltration and tissue organization(1,2). To control cell behaviour and ultimately induce structural and functional tissue formation on surfaces, planar substrates have been patterned with adhesion signals that mimic the spatial cues to guide cell attachment and function(3-5). The objective of this study is to create biochemical channels in 3D hydrogel matrices for guided axonal growth. An agarose hydrogel modified with a cysteine compound containing a sulphydryl protecting group provides a photolabile substrate that can be patterned with biochemical cues. In this transparent hydrogel we immobilized the adhesive fibronectin peptide fragment, glycine arginine - glycine - aspartic acid - serine(GRGDS), in selected volumes of the matrix using a focused laser. We verified in vitrothe guidance effects of GRGDS oligopeptide-modified channels on the 3D cell migration and neurite outgrowth. This method for immobilizing biomolecules in 3D matrices can generally be applied to any optically clear hydrogel, offering a solution to construct scaffolds with programmed spatial features for tissue engineering applications.