Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues.
Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues.
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在缺乏可灌流的血管网络的情况下，密集填充细胞的三维(3D)工程化组织很快就会形成坏死核。然而，缺乏一种通用的方法来快速构建这样的网络仍然是3D组织培养的主要挑战。在这里，我们打印了碳水化合物玻璃的刚性细丝网络，并将它们作为细胞相容的牺牲模板在含有活细胞的工程组织中生成圆柱形网络，该网络可以与内皮细胞排列在一起，并在高压脉动流动下向血液灌流。由于这种简单的血管铸型方法允许独立控制网络几何形状、内皮化和血管外组织，因此它与多种细胞类型、合成和天然细胞外基质(ECM)以及交联剂策略兼容。我们还证明，灌流的血管通道维持了原代大鼠肝细胞在工程化组织结构中的代谢功能，否则这些组织结构的核心功能会受到抑制。
In the absence of perfusable vascular networks, three-dimensional (3D) engineered tissues densely populated with cells quickly develop a necrotic core. Yet the lack of a general approach to rapidly construct such networks remains a major challenge for 3D tissue culture. Here, we 3D printed rigid filament networks of carbohydrate glass, and used them as a cytocompatible sacrificial template in engineered tissues containing living cells to generate cylindrical networks which could be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. Because this simple vascular casting approach allows independent control of network geometry, endothelialization, and extravascular tissue, it is compatible with a wide variety of cell types, synthetic and natural extracellular matrices (ECMs), and crosslinking strategies. We also demonstrated that the perfused vascular channels sustained the metabolic function of primary rat hepatocytes in engineered tissue constructs that otherwise exhibited suppressed function in their core.
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Tibbitt, Mark W.;Anseth, Kristi S.
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