Microfluidic assay of endothelial cell migration in 3D interpenetrating polymer semi-network HA-Collagen hydrogel

Microfluidic assay of endothelial cell migration in 3D interpenetrating polymer semi-network HA-Collagen hydrogel
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DOI:
10.1007/s10544-011-9541-7
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发表时间:
2011-08-01
影响因子:
2.8
通讯作者:
Lee, Sang-Hoon
Lee, Sang-Hoon
中科院分区:
工程技术3区
文献类型:
--
作者:
Jeong, Gi Seok;Kwon, Gu Han;Lee, Sang-Hoon

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细胞通过细胞外基质(ECM)的迁移是生理和病理过程如血管生成、癌症转移和伤口愈合的关键特征之一。特别是,在明确定义的三维(3D)微环境下的内皮细胞迁移的定量测定对于分析血管生成机制是重要的。在这项研究中,我们报告了一种微流控测定内皮细胞发芽和迁移到互穿聚合物半网络HA-胶原蛋白(SIPNs CH)水凝胶作为ECM,为细胞提供增强的体内模拟3D微环境。微流控芯片可以为细胞提供良好控制的生长因子梯度,而水凝胶可以模拟体内定义良好的3D微环境。(In此外,微流控芯片为细胞提供了良好控制的生长因子梯度)为此,制备了由胶原和透明质酸的半互穿网络组成的三种类型的水凝胶,并且我们首先证明了水凝胶在内皮细胞迁移中的作用。对水凝胶的扩散性能和溶胀率进行了表征。它以定量的方式调节内皮细胞的迁移,也受到基质金属蛋白酶(MMP)敏感的重塑肽和精氨酸-甘氨酸-赖氨酸(RGD)细胞粘附肽的额外合成的影响。我们成功地建立了一个新的细胞迁移平台,通过改变主要的决定因素,如ECM材料在生化合成和生长因子梯度下,在微流体的方式。
Cell migration through the extracellular matrix (ECM) is one of the key features for physiological and pathological processes such as angiogenesis, cancer metastasis, and wound healing. In particular, the quantitative assay of endothelial cell migration under the well-defined three dimensional (3D) microenvironment is important to analyze the angiogenesis mechanism. In this study, we report a microfluidic assay of endothelial cell sprouting and migration into an interpenetrating polymer semi-network HA-Collagen (SIPNs CH) hydrogel as ECM providing an enhanced in vivo mimicking 3D microenvironment to cells. The microfluidic chip could provide a well-controlled gradient of growth factor to cells, whereas the hydrogel could mimic a well-defined 3D microenvironment in vivo. (In addition/Furthermore, the microfluidic chip gives a well-controlled gradient of growth factor to cells) For this reason, three types of hydrogel, composed of semi-interpenetrating networks of collagen and hyaluronic acid were prepared, and firstly we proved the role of the hydrogel in endothelial cell migration. The diffusion property and swelling ratio of the hydrogel were characterized. It modulated the migration of endothelial cells in quantified manner, also being influenced by additional synthesis of Matrix metalloproteinase(MMP)-sensitive remodeling peptides and Arginine-glycine-lycinee (RGD) cell adhesion peptides. We successfully established a novel cell migration platform by changing major determinants such as ECM material under biochemical synthesis and under growth factor gradients in a microfluidic manner.