New developments and future trends of artificial blood

Artificial blood, better defined as oxygen therapeutic agents (OTAs), has been under investigation for over a century as an alternative to human donor blood because of certain drawbacks associated with allogeneic blood transfusions. These include blood shortages, storage limitations, infectious risks, immunological incompatibility, and adverse outcomes that are associated with allogeneic blood transfusion. Despite extensive research, there has been no artificial blood product developed for widespread use. However, recent developments show the emergence of new clinical applications. This review summarizes recent advances for hemoglobin-based oxygen carriers (HBOCs), perfluorocarbon (PFC) emulsions, hematopoietic stem cell (HSC)-derived red blood cells (RBCs), platelet substitutes, and nanoscale synthetic platforms. While functional oxygen transport has been established for earlier HBOC compounds, they have been limited by nitric oxide (NO) scavenging, vasoconstriction, oxidative damage, and an elevated risk of cardiovascular disease. PFC emulsions stand out by offering an alternative, chemically inert approach for oxygen transport that improves oxygen diffusion under low flow microcirculatory conditions, although their clinical translation has been hindered by physiological misconceptions and regulatory caution. HSC RBCs, particularly those generated by induced pluripotent stem cells (iPSCs), have established proof of concept in human trials in recent years; though scalability, enucleation rates, and expense are significant development hurdles. Parallel advances in platelet substitutes and hybrid nanotechnologies aim to address hemostatic support and whole-blood functionality. The review assesses the successes and failures of previous efforts and determines how hurdles may be overcome. Methods include encapsulation, hybrid modular blood surrogates, and artificial intelligence (AI)-designed molecules. Ethics, economic viability, and regulatory obstacles are also addressed. While artificial blood cannot yet replace donor transfusion for routine care, accumulating clinical data and technological convergence suggest increasing viability for niche indications such as trauma, battlefield medicine, and rare patient blood types. Continued progress in scalable manufacturing, safety optimization, and regulatory alignment will be essential to realizing donor-independent oxygen therapeutics.