Engineering RGD nanopatterned hydrogels to control preosteoblast behavior: A combined computational and experimental approach

Engineering RGD nanopatterned hydrogels to control preosteoblast behavior: A combined computational and experimental approach
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DOI:
10.1016/j.biomaterials.2007.06.018
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发表时间:
2007-10-01
期刊:
影响因子:
14
通讯作者:
Linderman, Jennifer J.
Linderman, Jennifer J.
中科院分区:
工程技术1区
文献类型:
--
作者:
Comisar, Wendy A.;Kazmers, Nikolas H.;Linderman, Jennifer J.

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粘附配体精氨酸-甘氨酸-天冬氨酸(RGD)已被偶联到各种材料中,用作组织培养基质或细胞移植载体,最近的研究表明,纳米图案化的RGD成高密度岛改变了关键的细胞行为。然而,以前的研究未能最终解耦的影响,RGD堆密度和个别模式参数(即RGD/岛和岛的分布)对这些改变细胞的反应。使用纳米图案化的RGD偶联藻酸盐水凝胶基质,这项工作结合了计算,统计和实验方法来阐明四个关键细胞反应的RGD模式的影响。这项研究表明,在MC 3 T3前成骨细胞中,粘着斑激酶(FAK)Y397磷酸化、细胞铺展和成骨分化可以通过RGD纳米图案化来控制,其中岛在整个水凝胶中的分布(即岛的间隔有多近)是最重要的图案参数。间隔较近的岛有利于FAK Y397磷酸化和细胞扩散,而间隔较宽的岛有利于分化。相反,增殖主要是RGD堆积密度的函数。细胞粘附配体的纳米图案化作为一种简单的工具具有巨大的潜力,可以显著控制工程化细胞外基质(ECM)中的多种细胞行为。(c)2007爱思唯尔有限公司保留所有权利。
The adhesion ligand arginine-glycine-aspartic acid (RGD) has been coupled to various materials to be used as tissue culture matrices or cell transplantation vehicles, and recent studies indicate that nanopatterning RGD into high-density islands alters key cell behaviors. Previous studies have failed, however, to conclusively decouple the effects of RGD bulk density and individual pattern parameters (i.e. RGDs/island and island distribution) on these altered cell responses. Using a nanopatterned RGD-coupled alginate hydrogel matrix, this work combines computational, statistical and experimental approaches to elucidate the effects of RGD patterns on four key cell responses. This study shows that in MC3T3 preosteoblasts focal adhesion kinase (FAK) Y397 phosphorylation, cell spreading, and osteogenic differentiation can be controlled by RGD nanopatterning, with the distribution of islands throughout the hydrogel (i.e. how closely spaced the islands are) being the most significant pattern parameter. More closely spaced islands favor FAK Y397 phosphorylation and cell spreading, while more widely spaced islands favor differentiation. Proliferation, in contrast, is primarily a function of RGD bulk density. Nanopatterning of cell adhesion ligands has tremendous potential as a simple tool to gain significant control over multiple cell behaviors in engineered extracellular matrix (ECM). (c) 2007 Elsevier Ltd. All rights reserved.