Artificial oxygen carriers (AOCs) have long been a focus of interest in several research areas. Red blood cell (RBC) storage lesions, transfusion side effects, and fragile blood supply during pandemics or wars are some reasons for shifting from blood substitution to AOCs. Moreover, AOCs could have other applications outside of blood substitution. The oxygen demand of high-density cultured cells during recombinant proteins production and limitations in delivering oxygen to all cells within the construct in tissue engineering make AOCs a center of attention. Thus, several types of oxygen carriers have been developed so far, which can be categorized into three types of stem cell-based, perfluorocarbon-based, and hemoglobin-based oxygen carriers (HBOCs). HBOCs are natural products derived mainly from outdated human RBC concentrates or bovine blood. For example, Hemospan/MP4OX, HbVesicles, ErythroMer, and HemoAct are some types of products derived from human hemoglobin. Also, Hemopure, Sanguinate, and OxyVita were derived from bovine hemoglobin. These products mostly have a central iron surrounded by tetrapyrroles. Crosslinking of hemoglobin strands, site-directed mutagenesis, and microencapsulation have been used to increase oxygen affinity and stabilize these products. Several clinical trials have been performed with these HBOCs, and some countries like South Africa and Russia approved Hemopure as an oxygen carrier. Nevertheless, side effects of these HBOCs, including inflammatory reactions, hypertension, and vasoconstriction, hindered their clinic entrance in most countries. Many efforts are now underway to develop new HBOCs derived from human and bovine and other animals with lower side effects.
In the past decade, lugworm and ragworm hemoglobin has also been introduced as alternative HBOCs. These worms are mainly large marine polychaetes worms of the phylum Annelida, which reside in burrows between low and high tide points. These segmented worms have giant hemoglobi