Physical and Chemical Signals That Promote Vascularization of Capillary-Scale Channels.
Physical and Chemical Signals That Promote Vascularization of Capillary-Scale Channels.
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DOI：
10.1007/s12195-016-0429-8
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发表时间：
2016-03-01
影响因子：
2.8
通讯作者：
Tien J
中科院分区：
文献类型：
--
作者：
Linville RM;Boland NF;Covarrubias G;Price GM;Tien J
适当的血管化对于工程组织的临床应用仍然至关重要。为了在体外设计微血管，我们和其他人通过预先形成的通道将内皮细胞递送到基于图案化的细胞外基质的凝胶中。这种方法受到悬浮中内皮细胞大小的限制，并导致直径低于约 30 μm 的通道被堵塞。在这里，我们研究了可以增强直接播种的物理和化学信号，目的是快速使毛细血管通道血管化。通过研究不同条件下 I 型胶原凝胶中的锥形微通道，我们确定刚性支架、正向压力和升高的环 AMP 水平可促进内皮稳定性，而反向压力可促进内皮迁移。我们将这些结果应用于均匀的 20 μm 直径通道，并优化压力、流量和剪切应力的大小，以最好地支持内皮迁移和血管稳定性。这种血管化策略能够在三天内形成毫米长的可灌注毛细血管。我们的结果表明如何操纵物理和化学环境来促进 I 型胶原凝胶内毛细血管通道的快速血管化。
Proper vascularization remains critical to the clinical application of engineered tissues. To engineer microvessels in vitro, we and others have delivered endothelial cells through preformed channels into patterned extracellular matrix-based gels. This approach has been limited by the size of endothelial cells in suspension, and results in plugging of channels below ~30 μm in diameter. Here, we examine physical and chemical signals that can augment direct seeding, with the aim of rapidly vascularizing capillary-scale channels. By studying tapered microchannels in type I collagen gels under various conditions, we establish that stiff scaffolds, forward pressure, and elevated cyclic AMP levels promote endothelial stability and that reverse pressure promotes endothelial migration. We applied these results to uniform 20-μm-diameter channels and optimized the magnitudes of pressure, flow, and shear stress to best support endothelial migration and vascular stability. This vascularization strategy is able to form millimeter-long perfusable capillaries within three days. Our results indicate how to manipulate the physical and chemical environment to promote rapid vascularization of capillary-scale channels within type I collagen gels.