School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Block N3, Singapore 639798.
Lab Chip. 2017 Aug 22;17(17):2960-2968. doi: 10.1039/c7lc00607a.
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) 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.
在微工程体外血管模型中，血管几何形状对于再现心血管疾病中血流诱导的内皮功能障碍和炎症的病理生理微环境非常重要。在此，我们提出了一种简单新颖的细胞外基质（ECM）水凝胶图案化方法，基于毛细爆裂阀（CBV）的概念来创建具有不同几何形状的可灌注血管化微通道。无需表面改性，并且该方法适用于包括胶原蛋白、基质胶和纤维蛋白在内的不同 ECM 类型。我们首先创建了胶原蛋白图案化的内皮细胞微通道，以研究屏障通透性和中性粒细胞跨内皮迁移，然后开发了仿生 3D 内皮-平滑肌细胞（EC-SMC）血管模型。我们观察到在炎症期间共培养模型中的屏障通透性显著降低，这表明周细胞在 ECM 重塑中的重要性。最后，我们设计了胶原蛋白图案化的狭窄血管微通道，以模拟动脉粥样硬化中的狭窄。全血以 1-10 达因厘米的剪切力灌注到微器件中，由于在狭窄处剪切应力增加，以及通过胶原蛋白的额外对流，观察到明显的血小板和白细胞黏附模式。总之，所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，用于实时研究心血管疾病中的血液动力学和细胞相互作用。
