OxyVita Hb is a new generation hemoglobin based oxygen carrier (HBOC) produced through modification of a zero-linked polymerization mechanism using activators which incorporate cross-linked bovine tetramer hemoglobin into “super-polymeric” macromolecules (Average molecular weight = 17 MDa) for the purpose of oxygen delivery when whole blood or packed red cells are not available. This molecular design approach was generated in order to address several fundamental biochemical and physiological weaknesses of previous generations of HBOCs. Observation during pre-clinical and clinical studies provided evidence that these early generation acellular HBOCs were directly associated with loss of retention within the circulatory system, extravasation across endothelial tissue membranes due to their small molecular size leading to arterial and venous vasoconstriction with coupled increases in mean arterial pressure (MAP). The inherent increase in molecular size and structural stability of the OxyVita Hb is a direct response to addressing these serious weaknesses that have occurred during the evolution of HBOC development within the past two decades. The nature of the zero-linked synthetic route eliminates any chemical linkers remaining in the product, eliminating side reaction concerns, such as reversibility and decomposition due to weak chemical bonds, dependency on temperature and pressure, and residual toxicity.

Blood transfusion is a routine yet resource-intensive medical procedure. Increasing global demand, limited donor availability, and logistical and ethical constraints have driven the search for adequate blood substitutes. Hemoglobin-based oxygen carriers (HBOCs) represent a promising class of therapeutics designed to mimic the oxygen transport function of red blood cells while overcoming the challenges of storage, compatibility, and infection risk. Despite decades of research, no HBOC has yet met all criteria for widespread clinical use. This review summarizes recent advances in the design and development of hemoglobin derivatives, with a focus on their biochemical properties, safety profiles, and oxygen delivery capabilities. We also discuss current limitations and translational barriers. The successful implementation of HBOCs could significantly improve transfusion strategies, especially in emergency medicine, military applications, and resource-limited settings. Continued innovation is essential to bring safe and effective oxygen therapeutics into routine clinical practice.

A study was conducted to compare the resistance to heme exposure between myoglobin, bovine hemoglobin, and OxyVita^®Hb (zero-link-hemoglobin-polymer). The rate of release of heme-iron is related to the tissue oxidative stress that can elicit deleterious effects in clinical uses of blood substitutes. Experimental work has focused on the unfolding of hemoglobin molecules, resulting in heme loss, by using urea as a denaturant and analyzing the Soret spectral region. These unfolding studies provide evidence for both the structural integrity and redox stability of OxyVita^®Hb and demonstrate that OxyVita^®Hb does not readily unfold and its heme exposure/release is greatly reduced.

Uncontrolled haemorrhage is one of the leading causes of death. This issue is present in controlled environments, such as hospitals, as well as pre-hospital and remote locations. Treatment is more challenging in remote locations where there is a lack of effective products to deliver oxygen and control coagulation. Poorly treated haemorrhage can lead to rapidly deteriorating bodily conditions that can result in organ failure and tissue death. Thus, the availability of products to support oxygen delivery to tissues and coagulation processes within the body is essential for the effective treatment of severe haemorrhage, particularly in out-of-the-hospital settings. The presence of such products would fill the gap that is currently present in emergency treatment. Promising results of an ex-vivo study on a novel haemoglobin-based oxygen carrier OxyVita^®C with coagulation capacity (OVCCC) are presented in this article. The proprietary protein protection technology allows for the powderization of protein components without changes in their characteristics and physiological activity. This technology was applied to the oxygen carrier OxyVita^®C, to plasma and to platelets. The functionality of all tested components, as well as a mixture of OxyVita^®C and platelets, was studied. The results suggest future clinical trials investigating the powderization of OVCCC, plasma and platelets are warranted. The development of this powderization method offers a huge advancement into a field in which no viable products exist.