Development of a vessel-on-a-chip model for study of Hb-based artificial oxygen carriers

Artificial oxygen carries (AOCs) can be used as red blood cell substitutes for transfusion to improve tissue oxygenation. They can be used to reduce transfusion-associated harmful side effects, such as inflammation and immunoreaction from the denoted blood. However, development of effective and safe AOCs to replace physiological human red blood cells (RBCs) is challenging. This work presents oxygen transport in transfusion of artificial oxygen carriers.  Hemoglobin based oxygen carriers were synthesized and their performance was tested. A 3D vessel on a chip device was developed to measure the oxygen transport in blood vessel.  In this model, each microfluidic chip consists of three channels, a center channel for loading an extracellular matrix (ECM), side by side perfusion channels for endothelium cell cultures. Endothelial cells were seeded on one side of ECM and serum-free medium containing AOCs was added to Endothelial cells channel. The same serum-free medium without Hb was added to another micro channel and Endothelial Cell permeability to Hemoglobin Based Oxygen Carriers was investigated. The response of endothelial layer permeability by comparing the cellular polymersomes vs. acellular HbOCs was tested. Additionally, the mechanical fatigue of AOCs was characterized by subjecting them to cyclic hypoxia and shear stresses at single-cell level.