Gas bioengineering using hemoglobin-vesicles for versatile clinical applications

Abstract: Blood transfusion systems have greatly benefited human health and welfare. Nevertheless, some problems remain: possibility of infection, blood type mismatching, immunological response, and a short shelf life that is insufficient for stockpiling for emergency situations. Realization of artificial O ₂ carriers is anticipated to solve such problems. During the long development of hemoglobin (Hb)-based O ₂ carriers, many side effects of cell-free Hb molecules have arisen, and have implied the physiological importance of the cellular structure of red blood cells (RBCs). Therefore, Hb-vesicles (HbVs) have been developed as artificial red cells that encapsulate a concentrated Hb solution in thin lipid bilayer vesicles. This Hb encapsulation can shield various toxic effects of molecular Hbs, especially reactions with endogenous NO and CO as vasorelaxation factors. Physicochemical analyses have clarified that Hb encapsulation retards these gaseous reactions significantly. "Gas Bioengineering" is intended to create systems using bioengineering and chemical engineering techniques to facilitate the transport of or regulate the concentration of endogenous or exogenous gaseous molecules (such as O ₂, NO, and CO) that are sometimes vital and sometimes toxic to humans. Gas bioengineering using HbVs underscores the potential of HbVs as a transfusion alternative and promises its use for other clinical applications that remain unattainable using RBC transfusion.