Biomimetic flowing vessel-on-a-chip recruiting glycocalyx features for investigating dexmedetomidine function

Endothelial glycocalyx dysregulation remains the leading cause of the development and progression of cardiovascular diseases, which can increase the risk of organ failure and even cause death. However, the construction of a reliable in vitro drug screening model system to investigate how to prevent glycocalyx degradation is still challenging. Herein, an advanced and biomimetic vessel-on-a-chip based on the inverse opal hydrogel film has been designed for endothelial glycocalyx research and drug evaluation. The inverse opal film, with ordered and uniform pore structures, is prepared through replicating the closely packed nanoparticle assemblies. The proposed vessel-on-a-chip is generated from the integration of an inverse opal film with a custom-designed microfluidic chip. Benefiting from the three-dimensional (3D) ordered porous structures of inverse opal films and the biomimetic dynamic in vivo environment of the chip, endothelial cells and smooth muscle cells can be co-cultured on the inverse opal film of this microfluidic chip for the endothelial glycocalyx study. Specifically, the results demonstrate that the glycocalyx layer is susceptible to degradation under low shear stress (LSS), whereas such dysregulation can be effectively prevented through the administration of dexmedetomidine anesthesia. Furthermore, the specific mechanism underlying this glycocalyx-preserving effect of dexmedetomidine is demonstrated to be associated with mitigation of the LSS-induced oxidative stress in endothelial cells, thereby attenuating mitochondrial apoptosis. These features reveal that our vessel-on-a-chip provides a promising platform for preclinical drug screening and evaluation in cardiovascular diseases.