Engineering of in vitro 3D capillary beds by self-directed angiogenic sprouting.

Engineering of in vitro 3D capillary beds by self-directed angiogenic sprouting.
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通过自导向的血管生成发芽的体外3D毛细管床的工程。

DOI:
10.1371/journal.pone.0050582
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kamm RD
Kamm RD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chan JM;Zervantonakis IK;Rimchala T;Polacheck WJ;Whisler J;Kamm RD

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近年来,微流控系统已被用于通过单层、线性或几何血管通道的模式来研究血管生成的基本方面。然而,在活体中,毛细血管存在于复杂的三维(3D)网络中,血管新生萌发在所有x、y、z平面上都具有一定程度的不可预测性。在体外生成能够支持厚厚生物组织的毛细血管床的能力,仍然是重要器官再生的关键挑战。在这里,我们报告了在体外微流控平台中设计的3D毛细血管床,该平台由生物相容的I型胶原凝胶组成,由海藻酸盐珠的机械框架支撑。设计的血管具有专利管腔,在设备上形成坚固的∼1.5 mm毛细血管网络,并支持通过设备灌流1微米荧光珠子。此外,藻酸盐微珠提供了一种模块化的方法来包裹和共培养细胞,这些细胞要么促进血管生成,要么需要在工程化组织结构中为细胞存活而灌流。这种实验室构建的血管供应对于以可扩展和模块化的方式构建毛细血管床和高阶生物组织的工程可能具有临床意义。
In recent years, microfluidic systems have been used to study fundamental aspects of angiogenesis through the patterning of single-layered, linear or geometric vascular channels. In vivo, however, capillaries exist in complex, three-dimensional (3D) networks, and angiogenic sprouting occurs with a degree of unpredictability in all x,y,z planes. The ability to generate capillary beds in vitro that can support thick, biological tissues remains a key challenge to the regeneration of vital organs. Here, we report the engineering of 3D capillary beds in an in vitro microfluidic platform that is comprised of a biocompatible collagen I gel supported by a mechanical framework of alginate beads. The engineered vessels have patent lumens, form robust ∼1.5 mm capillary networks across the devices, and support the perfusion of 1 µm fluorescent beads through them. In addition, the alginate beads offer a modular method to encapsulate and co-culture cells that either promote angiogenesis or require perfusion for cell viability in engineered tissue constructs. This laboratory-constructed vascular supply may be clinically significant for the engineering of capillary beds and higher order biological tissues in a scalable and modular manner.
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