Vascular Microphysiological System for Investigating Endothelial Barrier Function during Organ Preservation and Reperfusion

Abstract

Endothelial cell damage after cold preservation and reperfusion injury causes deterioration of the endothelial barrier and ultimately results in edema, leading to transplant failure. Here, we introduce a vascular microphysiological system (MPS) as a testbed to investigate the combinational effect of thermal and fluid perturbations (i.e., wall shear stress) on human endothelial barrier function. We compared two methods of organ storage: isochoric supercooling (ISC) preservation, which prevents ice formation at subzero temperatures; and, the standard clinical protocol of static cold storage (SCS) at 4 ^°C. Integrating electrical impedance measurements on chip allowed real-time monitoring and quantification of barrier function during preservation and reperfusion protocols. Isochoric supercooling preservation enabled longer periods of preservation with superior recovery of barrier function during reperfusion, and had lower metabolic activities compared to static cold storage. Genomic analysis revealed injury and recovery mechanisms at the molecular level for the different preservation and reperfusion conditions. The multifunctional vascular microphysiological system provided a physiologically relevant in vitro model recapitulating ischemia-reperfusion injury to the endothelium. The vascular MPS has potential for optimizing organ preservation protocols, ultimately improving organ transplant viability.