Red blood cells (RBCs) circulate through the body for over 120 days before loss of flexibility causes them to be removed from the bloodstream. Synthetic particles with similarly long circulation times are desirable for many applications including medical contrast agents, synthetic oxygen carriers, and drug delivery vectors. A biomimetic approach is taken to the design of synthetic red blood cells (RBCs) using a powerful nano-molding technique called PRINT (Particle Replication in Non-wetting Templates). PRINT is used to synthesize shape-specific, colloidally stable, hydrogel particles with dimensions and mechanical properties which resemble red blood cells and that are individually deformable in a manner which should allow these seven micron diameter discs to pass through the three micron sized sinusoids in the spleen. Previous approaches for the design of synthetic blood have focused on i) fluorocarbon emulsions which can dissolve large amounts of blood gases; ii) PEGylated hemoglobin; and iii) liposomal delivery of hemoglobin. Heretofore, no one has reported direct molding of RBC mimics which have the same evolutionarily designed shapes and deformability or modulus as RBCs. The PRINT molding technique allows us to independently design and investigate the key criteria necessary for a true replacement for blood, including: shape control, particle modulus or flexibility, surface chemistry and surface ligands, flow characteristics and gas transport characteristics. Design of a polymeric matrix to match the extremely low modulus of RBCs while maintaining the material strength to survive the shear stresses involved in blood flow is reported. An initial biodistribution study of these RBC mimic particles shows enhanced circulation compared to rigid discs of the same size and surface chemistry.