Biosynthetic blood surrogates: Current status and future opportunities

Blood is a liquid connective tissue containing cellular and non-cellular components. Blood circulation is vital to life since it transports gases and nutrients, maintains immune surveillance, promotes necessary clotting to prevent hemorrhage, and maintains oncotic pressure and body temperature. Blood transfusion is a life-saving procedure where donor-derived blood is administered into a patient when the patient's own blood is diseased or depleted. However, blood transfusion faces tremendous challenges due to donor shortage, limited shelf life, transfusion-associated infection risks, and complex logistics of blood banking and transport. A robust volume of research is currently focused on resolving these issues, including pathogen reduction technologies, temperature-reduced storage, and bioreactor-based production of blood cells from stem cells in vitro. In parallel, significant interest has developed toward biomaterials-based engineering of synthetic blood surrogates that can provide critical functions of blood components while circumventing the limitations of donor-derived blood products. Here, the major efforts have focused on the design of RBC surrogates for oxygen transport and platelet surrogates for hemostatic functions, and only limited efforts have focused on WBC mimicry. Processes have also been developed to isolate plasma or coagulation factors to treat specific bleeding risks, as well as freeze-dry or spray-dry plasma for long-term storage and on-demand use. The current article will provide a comprehensive review of various blood surrogate approaches highlighting biomaterials design and applications, important challenges, and future opportunities.