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Design and assembly considerations in the engineering of vascular tissue.

机译：血管组织工程中的设计和组装注意事项。

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摘要

Native vascular tissue functions are highly dependent on structural organization at the super-cellular, cellular, and sub-cellular spatial scales. We hypothesized that the structure-function relationship of vascular tissues in vivo can be leveraged to engineer vascular tissues in vitro by prescribing the shape of constituent cells and their assembly into organized three-dimensional structures. To this end, we first asked if vascular smooth muscle cell shape influences cellular contractility. We engineered human vascular smooth muscle cells to assume similar shapes to those in elastic and muscular arteries and then measured their contraction while stimulating with endothelin-1. We found that vascular smooth muscle cells with elongated shapes exhibited lower contractile strength but a greater percentage increase in contraction after endothelin-1 stimulation, suggesting that elongated vascular smooth muscle cell shape endows the muscular artery with greater dynamic contractile range. Next, we sought to assemble cells into tissues by employing a three-dimensional cellular patterning strategy based on the folding of porous, thin polymer films. We assembled different three-dimensional endothelial and vascular smooth muscle organizations by patterning two-dimensional poly(lactic-co-glycolic) acid and collagen thin films with cell suspensions at prescribed locations. The films were subsequently folded following Miura-ori geometry guidelines and the matrices were embedded subcutaneously in immunodeficient mice in order to assess the vascularization of the implanted constructs. We found that spatial organization that allowed endothelial and vascular smooth muscle cells to interact adjacent to each other laterally in the same folding plane created the densest vascularized network, suggesting that three-dimensional structural organization of vascular cells can influence the formation of vascularized networks. Taken together, our result shows that functional vascular tissues in vitro can be engineered by encoding structure cues in their design and assembly.
机译：天然血管组织功能高度依赖于超细胞，细胞和亚细胞空间尺度的结构组织。我们假设通过规定组成细胞的形状及其组装成有组织的三维结构，可以利用体内血管组织的结构-功能关系来体外工程化血管组织。为此，我们首先询问血管平滑肌细胞的形状是否影响细胞的收缩性。我们设计了人类血管平滑肌细胞，使其形状与弹性和肌肉动脉中的形状相似，然后在用内皮素-1刺激时测量它们的收缩。我们发现内皮素-1刺激后，具有细长形状的血管平滑肌细胞表现出较低的收缩强度，但收缩百分比增加，这表明细长的血管平滑肌细胞形状赋予肌肉动脉更大的动态收缩范围。接下来，我们试图通过基于多孔薄聚合物膜折叠的三维细胞图案化策略将细胞组装成组织。我们通过在指定位置用细胞悬液对二维聚乳酸-乙醇酸和胶原蛋白薄膜进行图案化，组装了不同的三维血管内皮和血管平滑肌组织。随后按照Miura-ori几何准则将膜折叠，并将基质皮下植入免疫缺陷小鼠中，以评估植入构建体的血管形成。我们发现，允许内皮细胞和血管平滑肌细胞在同一折叠平面内横向相邻相互作用的空间组织产生了最密集的血管化网络，这表明血管细胞的三维结构组织可以影响血管化网络的形成。综上所述，我们的结果表明，可以通过在设计和组装过程中编码结构线索来对体外功能性血管组织进行工程改造。

著录项

  • 作者

    Ye, Jin Cheng.;

  • 作者单位

    Harvard University.;

  • 授予单位 Harvard University.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 169 p.
  • 总页数 169
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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