Modified hemoglobin-based blood substitutes: crosslinked, recombinant and encapsulated hemoglobin.

Native hemoglobin in the form of stroma-free hemoglobin cannot be used as blood substitute. Hemoglobin has to be modified either molecularly or encapsulated. First generation molecularly modified ultrapure hemoglobins are now in clinical trial--some in Phase III. There are a number of these. Polyhemoglobin is formed by crosslinking hemoglobin molecules intermolecularly and intramolecularly. A crosslinked single hemoglobin molecule is formed by crosslinking hemoglobin intramolecularly. Recombinant hemoglobin from E.coli is formed by fusion of the subunits of each hemoglobin molecule. Conjugated hemoglobin is formed by crosslinking each hemoglobin molecule to soluble polymers. A second generation system formed by crosslinking hemoglobin-superoxide dismutase-catalase is being developed. A third generation hemoglobin-based blood substitute is based on microencapsulated hemoglobin, artificial red blood cells, that more closely resemble a complete red blood cell.