Hemoglobin-based oxygen carrier: What we have learned and where we are heading?

A portable, universal, easy-to-preserve alternative of human red blood cells (RBC) has been pursued for decades in order to expand the limited blood supply, with Hemoglobin-Based Oxygen Carrier (HBOC) being one of the most promising techniques. Through two generations of development, various HBOC products were designed to emulate the natural RBCs with better biochemical and physical properties, but their over-ambitious product positioning and irrational clinical designs impeded their final approval. Now in its third generation, HBOC is finally poised for its commercialization with clearer views on a proper indication for use. Here, we review the development of HBOC, update the current pipeline and outline key lessons we have learned through past failures. We also specify its use scenario and propose future development to provide a more complete picture of the past, present and future of HBOC.