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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Vascularized organoid engineered by modular assembly enables blood perfusion
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Vascularized organoid engineered by modular assembly enables blood perfusion

机译：通过模块化组装设计的血管化类器官可实现血液灌注

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摘要

Tissue engineering is one approach to address the donor-organ shortage, but to attain clinically significant viable cell densities in thick tissues, laboratory-constructed tissues must have an internal vascular supply. We have adopted a biomimetic approach and assembled microscale modular components, consisting of submillimeter-sized collagen gel rods seeded with endothelial cells (ECs) into a (micro)vascularized tissue; in some prototypes the gel contained HepG2 cells to illustrate the possibilities. The EC-covered modules then were assembled into a larger tube and perfused with medium or whole blood. The interstitial spaces among the modules formed interconnected channels that enabled this perfusion. Viable cell densities were high, within an order of magnitude of cell densities within tissues, and the percolating nature of the flow through the construct was evident in microcomputed tomography and Doppler ultrasound measurements. Most importantly, the ECS retained their nonthrombogenic phenotype and delayed clotting times and inhibited the loss of platelets associated with perfusion of whole blood through the construct. Unlike the conventional scaffold and cell-seeding paradigm of other tissue-engineering approaches, this modular construct has the potential to be scalable, uniform, and perfusable with whole blood, circumventing the limitations of other approaches.
机译：组织工程学是解决供体器官短缺的一种方法，但是要在厚组织中获得临床上显着的活细胞密度，实验室构建的组织必须具有内部血管供应。我们采用了仿生方法，并组装了微型模块化组件，该组件由亚毫米大小的胶原凝胶棒和内皮细胞（EC）植入到（微）血管化组织中组成；在某些原型中，凝胶含有HepG2细胞以说明可能性。然后将EC覆盖的模块组装到更大的试管中，并灌注中等或全血。模块之间的间隙空间形成了使该灌注能够进行的互连通道。活细胞密度很高，处于组织内一定数量的细胞密度范围内，在微计算机断层扫描和多普勒超声测量中，流经构建体的渗流性质十分明显。最重要的是，ECS保留了其非血栓形成表型并延迟了凝血时间，并抑制了与通过构建体灌注全血相关的血小板损失。与其他组织工程方法的常规支架和细胞播种范例不同，这种模块化结构具有可扩展，统一和可灌注全血的潜力，从而规避了其他方法的局限性。

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