Advancing battlefield and global blood supply solutions by novel magnetoporation: Superior trehalose delivery to create functional lyophilized red blood cells

A reliable blood supply for resuscitation is a critical component of any healthcare setting. Hemorrhage is a leading cause of preventable death in both military and civilian trauma care [1]. In the battlefield, of the ~4000 pre-hospital deaths recorded by the U.S. Military from October 2001 to June 2011, 24% were potentially preventable; of these, hemorrhage was the predominant cause in 91% of cases [2]. Globally, supply lags farbehind demand, particularly in remote areas and underdeveloped countries as well as during natural disasters and pandemics. The estimated worldwide unmet need is 100 million units per year [3]. Supply relies first on blood donation, which in turn requires an infrastructure as well as healthy and willing donors and is further complicated by limitations in storage and transport to points of need. Thus, techniques for blood preservation are imperative. Individual blood components offer the following advantages over whole blood: less complex screening; optimal storage conditions for each component; and precision resuscitation based on needs and hence more efficient use of a limited resource. Among blood components, red blood cells (RBCs) are the most commonly transfused, with about 15 million units transfused annually in the U.S. and 85 million units transfused annually worldwide [4]. Current RBC biopreservation approaches include refrigeration, cryopreservation, and lyophilization. Lyophilization, also known as freeze-drying, is a process by which water is removed from a product after freezing. áCritical to a viable lyophilized cellular product is the maintenance of membrane porosity, structural integrity, and thermodynamic stability throughout the freezing, drying, and rehydration steps. A number of cryoprotective compounds have been shown to offer such biostability for other cell types. Trehalose is one such compound of particular interest given its excellent protective effects upon freezing and dehydration and has been approved as safe by all international and national food regulatory authorities, including the Food & Drug Administration (FDA). Sigma Genetics envisions obtaining FDA regulatory approval and a licensable process to manufacture lyophilized trehalose-stabilized RBCs products at scale, freeze-dried in sterile plastic bags replete with ports and tubing allowing for rapid rehydration and transfusion in austere environments. This dual use technology will supply domestic and international blood banks and play an impactful role as a source of functional RBCs to treat hemorrhagic shock, cancer related anemia and sickle cell anemia. Importantly, accomplishing these fundamental product development goals is a prerequisite for lyophilization of whole blood and a prospective 1:1:1 (RBC: platelet:plasma) lyophilized component replacement product.