Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea.
Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology (POSTECH), San 31, Hoyja-dong, Nam-Gu, Pohang, Gyeongbuk, 37673, South Korea.
Biomaterials. 2018 Jul;169:22-34. doi: 10.1016/j.biomaterials.2018.03.053. Epub 2018 Mar 31.
Leukocyte infiltration plays critical roles in tissue inflammation for pathogen clearance and tumor eradication. This process is regulated by complex microenvironments in blood vessels, including inflamed endothelium, blood flow, and perivascular components. The role of perivascular components in leukocyte infiltration has not been systematically investigated until recently mostly due to lack of technology. In this work, we developed a three-dimensional multi-layered blood vessel/tissue model with a nanofiber membrane, enabling real-time visualization of dynamic leukocyte infiltration and subsequent interaction with perivascular macrophages. We directly fabricated a highly aligned, free-standing nanofiber membrane with an ultra-thin thickness of ∼1 μm in microfluidic systems. Coating the nanofiber membrane with matrigel showed synergetic topographical and biochemical effects on the reconstitution of a well-aligned endothelial monolayer on the membrane. Our 3D multi-layered blood vessel/tissue model will offer a powerful and versatile tool for investigating the mechanism of leukocyte tissue infiltration and subsequent immune responses.
白细胞浸润在清除病原体和肿瘤清除方面对组织炎症起着关键作用。这个过程受到血管内复杂微环境的调节，包括发炎的内皮细胞、血流和血管周围成分。直到最近，由于缺乏技术，血管周围成分在白细胞浸润中的作用还没有被系统地研究过。在这项工作中，我们开发了一种具有纳米纤维膜的三维多层血管/组织模型，能够实时可视化动态白细胞浸润及其与血管周围巨噬细胞的后续相互作用。我们直接在微流控系统中制造了具有超高取向度、独立的纳米纤维膜，厚度约为 1μm。在纳米纤维膜上涂覆基质胶，对在膜上重建排列良好的内皮单层具有协同的形貌和生化效应。我们的三维多层血管/组织模型将为研究白细胞组织浸润及其后续免疫反应的机制提供一个强大而通用的工具。
