Blood Substitutes

Abstract

The development of oxygen (O2) carrying blood substitutes has evolved from the goal of replicating blood O2 transports properties to that of preserving microvascular and organ function, reducing the inherent or potential toxicity of the material used to carry O2, and treating pathologies initiated by anemia and hypoxia. Furthermore, the emphasis has shifted from blood replacement fluid to “O2 therapeutics” that restore tissue oxygenation to specific tissues regions. This review covers the different alternatives, potential and limitations of hemoglobin based O2 carriers (HBOCs) and perfluorocarbon based O2 carriers (PFCOCs), with emphasis on the physiological conditions disturbed in the situation that they will be used. It describes how concepts learned from plasma expanders without O2 carrying capacity can be applied to maintain O2 delivery and summarizes the microvascular responses due to HBOCs and PFCOCs. This review also presents alternative applications of HBOCs and PFCOCs namely: 1) How HBOC O2 affinity can be engineered to target O2 delivery to hypoxic tissues; and 2) How the high gas solubility of PFCOCs provides new opportunities for carrying, dissolving and delivering gases with biological activity. It is concluded that current blood substitutes development has amplified their applications horizon by devising therapeutic functions for oxygen carriers requiring limited O2 delivery capacity restoration. Conversely, full, blood-like O2 carrying capacity re-establishment awaits control of O2 carrier toxicity.

2H,3H-Decafluoropentane-Based Nanodroplets: New Perspectives for Oxygen Delivery to Hypoxic Cutaneous Tissues

“…To overcome this problem, intensive research is being pursued to develop new carriers able to release therapeutically significant amounts of oxygen to tissues in an effective and time-sustained manner [ 12 , 13 ]. Hemoglobin (Hb)-based oxygen carriers have been developed as cell-free suspensions, either encapsulated within vehicles, or complexed with protective enzymes [ 12 , 13 ]. Alternative carriers are based on perfluorocarbons, which can carry molecular oxygen without actually binding it, thus favoring gas exchange [ 14 ].…”

“…Alternative carriers are based on perfluorocarbons, which can carry molecular oxygen without actually binding it, thus favoring gas exchange [ 14 ]. However, they are not water-miscible, and therefore need to be formulated into emulsions for in vivo use [ 12 , 14 ]. Unfortunately, despite attractive characteristics, no perfluorocarbon-based oxygen emulsion is currently approved for clinical uses: some of them, such as Fluosol-DA, have failed due to secondary effects of the surfactants employed, whereas others, such as Oxygent, displayed adverse cerebrovascular effects on cardiopulmonary bypass [ 14 ].…”

Resuscitation from hemorrhagic shock using polymerized hemoglobin compared to blood

“…In addition, the availability of blood is limited in emergency situations such as in war zones or after natural disasters (5). Therefore, the development of a therapeutic product that can suitably replace blood transfusion in cases of severe hemorrhage or during major cardiovascular surgery has been a goal of scientific and commercial efforts (6). Hemoglobin, the protein responsible for the transport of O 2 in the RBC, has served as the precursor for the formulation of blood substitutes.…”

“…From the first generation of HBOCs, we learned that acellular Hb depletes endothelial nitric oxide (NO) via a NO dioxygenase reaction that produces vasoconstriction and hypertension (13, 14). Other negative reactions partially responsible for vasoconstriction and hypertension exerted by first generation HBOCs were the extravasation of acellular Hb due to its small molecular size, as well as metabolic regulation of blood flow in response to hyper-oxygenation due to facilitated O 2 transport by the acellular Hb (15, 16). To overcome these issues, different strategies have been developed, including Hb polymerization and Hb surface decoration with polyethylene glycol (PEG) (17).…”

Liquid Perfluorochemicals as Flexible and Efficient Gas Carriers Applied in Bioprocess Engineering: An Updated Overview and Future Prospects

“…PFC-in-water emulsions intended for biomedical use are produced at concentrations ranging from 20 % up to 120 % weight/volume. Osmolarity of the suspending media is independent of liquid PFC concentration and is adjusted by the addition of tonicity agents (Cabrales and Intaglietta, 2013). Up to date, several emulsion systems based on a few liquid PFC agents have been commercially developed and they are generally in preclinical/clinical trials, as reported in Table 3 plant-origin additives, α-tocopherol).…”