Arterial Internal Elastic Lamina-Inspired Membrane for Providing Biochemical and Structural Cues in Developing Artery-on-a-Chip

In vitro 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 in vivo 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 in vivo 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.