I-Corps: Developing polymerized hemoglobin using enzymatic ligation

University Of California-San Diego, La Jolla CA

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is the development of a blood substitute for use in veterinary and human applications. The demand for donated blood is rising due to global catastrophes such as war, natural disasters, and pandemics/endemics. Additionally, the military may have interest in field-ready oxygen (O2) carriers that can provide an alternative solution to impractical blood transfusions for cases of hemorrhagic shock in the field that may lead to severe blood loss. The current clinical standard for resuscitation from trauma and the absence of blood is the use of crystalloids, such as lactated Ringer’s solution. Crystalloids are widely available, safe, and inexpensive. These solutions are used to restore blood volume and blood pressure, allowing blood flow to continue, but do not have (O2)-carrying capacity and have varying negative effects on blood flow and O2 delivery. The ideal resuscitation fluid needs to be able to maintain blood volume and blood pressure, without excessively diluting O2-carrying capacity, and plasma proteins, or reducing blood viscosity. The proposed technology offers an alternative approach to blood substitutes, termed “O2 bridges”, or hemoglobin-based oxygen carrier (HBOC). HBOCs have the potential to be engineered to replicate, or even optimize the critical biophysical parameters of circulating blood, enabling the production of a life-sustaining product. The proposed technology is designed to transport O2 to tissues as effectively as whole blood or packed red blood cells. In addition, this HBOC solution may perform this function without the risk of disease transmission, transfusion reactions, or other transfusion-related complications. This I-Corps project is based on the development of a hemoglobin-based oxygen carrier that is produced from expired donated human blood. The proposed technology uses enzymatic ligation (transglutaminase) to produce large-size polymerized human hemoglobin (PolyhHb). In this process, red blood cells are stripped from their membrane leaving the hemoglobin protein to be purified and processed into a functional biocompatible solution. Large, polymerized hemoglobin-based oxygen carrier (HBOC) solutions have the advantage of longer circulatory half-life indicative of the difference in markers of systemic and reticuloendothelial iron transport. This technology has been tested in small animals and has shown promising results in anemic conditions. In addition, it has been tested against other HBOC designs and other blood products. The proposed technology may be used to create a functional HBOC solution that has practical use in uncontrollable hemorrhage environments. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.