Bio-Inspired Artificial Red Blood Cell: Design, Pre-Clinical Results and Novel Indications

In blood, the primary role of RBCs is to transport oxygen and to regulate regional blood flow distribution, via highly regulated mechanisms. In the setting of exsanguinating haemorrhage or severe anemia, RBC loss may critically restrict tissue oxygenation and result in morbidity and mortality. In such cases, transfusion of whole blood or RBCs can significantly improve survival. However, blood products including RBCs have limited availability and portability and present additional challenges related to type matching, pathogenic contamination risks, and short shelf-life. These issues lead to substantial logistical barriers to their pre-hospital use or in austere battlefield and remote civilian conditions. To date, efforts to develop hemoglobin (Hb) based oxygen carriers (HBOCs) have failed, because of design flaws which do not preserve physiologic interactions of Hb with: O2 (they capture O2 in lungs, but do not release O2 effectively to tissue) and nitric oxide (NO) (they trap NO, causing vasoconstriction). While robust efforts are underway to resolve these issues, recent research breakthroughs have led to bio-inspired engineering of RBC surrogates, using various cross-linked, polymeric and encapsulated Hb in the form of 'bio-synthetic RBC surrogates'. These 'next-generation' Hb-based oxygen carriers (HBOCs) can potentially provide therapeutic oxygenation when whole blood or RBC are not available. This talk will comprehensively review both historical and new HBOC designs, including current state-of-the-art and novel bio-inspired artificial RBC designs in development, along with a critical discussion of successes and challenges in this field.