Youn Jaeseung, Han Hyeonseok, Park Sang Min, Kim Dong Sung
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea.
School of Mechanical Engineering, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241, South Korea.
ACS Macro Lett. 2021 Nov 16;10(11):1398-1403. doi: 10.1021/acsmacrolett.1c00551. Epub 2021 Oct 20.
artery models constructed on a membrane-based microfluidic chip, called an artery-on-a-chip, have been spotlighted as a powerful platform for studying arterial physiology. However, due to the use of a flat and porous membrane that cannot mimic the internal elastic lamina (IEL), the physiological similarity in the phenotypes and the arrangements of the endothelial cells (ECs) and aortic smooth muscle cells (AoSMCs) has been limited in the previously developed artery-on-a-chips. Herein, we developed an innovative membrane mimicking the structures of IEL by utilizing electrospun aligned silk fibroin/polycaprolactone nanofiber membranes. An arterial IEL-mimicking (AIM) membrane was about 5 μm thick and composed of orthogonally aligned nanofibers with a diameter of around 400 nm, which were highly comparable to the IEL. Such structural similarity was found to induce the ECs and SMCs to be elongated and orthogonally aligned as in the artery. In particular, the SMCs cultured on the AIM membrane maintained a healthy state showing increased αSMA mRNA expression, which was easily lost on the conventional membrane. We constructed an AIM membrane-integrated artery-on-a-chip having an orthogonal arrangement of ECs and SMCs, which was desirable but difficult to be realized with the previous artery-on-a-chip.
基于膜的微流控芯片构建的动脉模型,即所谓的“芯片上的动脉”,已成为研究动脉生理学的强大平台而备受关注。然而,由于使用的是无法模拟内弹性膜(IEL)的扁平多孔膜,在先前开发的“芯片上的动脉”中,内皮细胞(ECs)和主动脉平滑肌细胞(AoSMCs)的表型及排列方面的生理相似性受到限制。在此,我们利用静电纺丝排列的丝素蛋白/聚己内酯纳米纤维膜开发了一种模仿IEL结构的创新膜。一种模仿动脉IEL的(AIM)膜约5μm厚,由直径约400nm的正交排列纳米纤维组成,与IEL高度可比。发现这种结构相似性可诱导ECs和平滑肌细胞如在动脉中一样伸长并正交排列。特别是,在AIM膜上培养的平滑肌细胞保持健康状态,显示αSMA mRNA表达增加,而在传统膜上这种表达很容易丧失。我们构建了一种具有ECs和平滑肌细胞正交排列的集成AIM膜的“芯片上的动脉”,这在先前的“芯片上的动脉”中是理想但难以实现的。