Biomimetic human small muscular pulmonary arteries
Biomimetic human small muscular pulmonary arteries
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DOI：
10.1126/sciadv.aaz2598
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发表时间：
2020-03-01
期刊：
影响因子：
13.6
通讯作者：
Romer, Lewis H.
中科院分区：
文献类型：
--
作者：
Jin, Qianru;Bhatta, Anil;Romer, Lewis H.
肌性小动脉的结构和功能变化在肺动脉高压的病理生理学中起着重要作用，肺动脉高压是一个新兴的公共卫生挑战。迫切需要改进这些微血管的解剖学模拟体外模型，因为非人类血管和以前的模型不能准确地概括人类微血管壁的微环境和结构。在这里，我们描述了平行的生物织物的可调尺寸和基础设施的自卷仿生肺动脉微血管。这些微血管具有解剖学上精确的分层和排列的人平滑肌细胞、细胞外基质和内皮细胞的图案，并且表现出内皮寿命和一氧化氮产生的显著增加。计算图像处理产生了细胞和蛋白质的高分辨率3D透视图。我们的研究为工程多细胞组织提供了一个新的范例，在平面部分中精确的3D空间定位的多个成分，为人类疾病中的微血管病理生物学的研究提供了一个仿生平台。
Changes in structure and function of small muscular arteries play a major role in the pathophysiology of pulmonary hypertension, a burgeoning public health challenge. Improved anatomically mimetic in vitro models of these microvessels are urgently needed because nonhuman vessels and previous models do not accurately recapitulate the microenvironment and architecture of the human microvascular wall. Here, we describe parallel biofabrication of photopatterned self-rolled biomimetic pulmonary arterial microvessels of tunable size and infrastructure. These microvessels feature anatomically accurate layering and patterning of aligned human smooth muscle cells, extracellular matrix, and endothelial cells and exhibit notable increases in endothelial longevity and nitric oxide production. Computational image processing yielded high-resolution 3D perspectives of cells and proteins. Our studies provide a new paradigm for engineering multicellular tissues with precise 3D spatial positioning of multiple constituents in planar moieties, providing a biomimetic platform for investigation of microvascular pathobiology in human disease.