Micro-engineered perfusable 3D vasculatures for cardiovascular diseases
Micro-engineered perfusable 3D vasculatures for cardiovascular diseases
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DOI：
10.1039/c7lc00607a
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发表时间：
2017-09-07
期刊：
影响因子：
6.1
通讯作者：
Hou, Han Wei
中科院分区：
文献类型：
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作者：
Menon, Nishanth Venugopal;Tay, Hui Min;Hou, Han Wei
微工程化体外血管模型中的血管几何形状对于再现心血管疾病中流动诱导的内皮功能障碍和炎症研究的病理生理微环境是重要的。在此，我们提出了一种简单而新颖的细胞外基质（ECM）水凝胶图案化方法，以创建基于毛细血管破裂阀（CBV）的概念的不同几何形状的可灌注血管化微通道。不需要表面改性，并且该方法适用于不同的ECM类型，包括胶原蛋白、基质胶和纤维蛋白。我们首先创建了胶原蛋白图案化的内皮化微通道，以研究屏障渗透性和中性粒细胞跨内皮迁移，随后开发了仿生3D内皮-平滑肌细胞（EC-SMC）血管模型。我们观察到在炎症期间在共培养模型中屏障通透性的显著降低，这表明血管周围细胞在ECM重塑中的重要性。最后，我们设计了胶原蛋白图案的收缩血管微通道来模拟动脉粥样硬化的狭窄。将全血灌注（1-10 dyne cm（-2））到微型装置中，由于收缩处的剪切应力增加以及通过胶原的额外对流，观察到不同的血小板和白细胞粘附模式。总之，开发的水凝胶图案化技术能够在器官芯片微系统中形成独特的病理生理结构，用于心血管疾病中血流动力学和细胞相互作用的实时研究。
Vessel geometries in microengineered in vitro vascular models are important to recapitulate a pathophysiological microenvironment for the study of flow-induced endothelial dysfunction and inflammation in cardiovascular diseases. Herein, we present a simple and novel extracellular matrix (ECM) hydrogel patterning method to create perfusable vascularized microchannels of different geometries based on the concept of capillary burst valve (CBV). No surface modification is necessary and the method is suitable for different ECM types including collagen, matrigel and fibrin. We first created collagen-patterned, endothelialized microchannels to study barrier permeability and neutrophil transendothelial migration, followed by the development of a biomimetic 3D endothelial- smooth muscle cell (EC-SMC) vascular model. We observed a significant decrease in barrier permeability in the co-culture model during inflammation, which indicates the importance of perivascular cells in ECM remodeling. Finally, we engineered collagen-patterned constricted vascular microchannels to mimic stenosis in atherosclerosis. Whole blood was perfused (1-10 dyne cm(-2)) into the microdevices and distinct platelet and leukocyte adherence patterns were observed due to increased shear stresses at the constriction, and an additional convective flow through the collagen. Taken together, the developed hydrogel patterning technique enables the formation of unique pathophysiological architectures in organ-on-chip microsystems for real-time study of hemodynamics and cellular interactions in cardiovascular diseases.