Highly Loaded Hemoglobin Spheres as Promising Artificial Oxygen Carriers

Seeking safe and effective artificial blood substitutes based on hemoglobin (Hb) as oxygen carriers is an important topic. A significant challenge is to enhance the loading content of Hb in a well-defined structure. Here we report a facile and controllable avenue to fabricate Hb spheres with a high loading content by templating decomposable porous CaCO3 particles in collaboration with covalent layer-by-layer assembly technique. The surface of the Hb spheres was further chemically modified by biocompatible polyethylene glycol to protect and stabilize the system. Multiple characterization techniques were employed to reveal the loading and density of Hb in an individual CaCO3 particle. The results demonstrate that the strategy developed in this work is effective and flexible for construction of the highly loaded Hb spheres. More importantly, such Hb spheres retain their carrying–releasing oxygen function. It may thus have great potential to develop Hb spheres with highly loaded content as realistic artificial blood substitutes in the future.