Fabrication of oxygen-releasing dextran microgels by droplet-based microfluidic method

In the tissue engineering field, the supply of oxygen to three-dimensional (3D) tissues is an important aspect to avoid necrosis due to hypoxia. Although oxygen-releasing bulk materials containing calcium peroxide (CaO₂, CP) have attracted much attention, micrometer-sized oxygen-releasing soft materials would be advantageous because of their highly controllable structures, which can be applied for cell scaffolds, injectable materials, and bioink components in 3D bioprinting. In this study, oxygen-releasing microgels were fabricated via a droplet-based microfluidic system. Homogeneous, monodisperse and stable oxygen-releasing microgels were obtained by photo-crosslinking of droplets composed of biocompatible dextran modified with methacrylate groups and CP nanoparticles as an oxygen source. We also used our microfluidic system for the in situ amorphous calcium carbonate (CaCO₃, ACC) formation on the surface of CP nanoparticles to achieve the controlled release of oxygen from the microgel. Oxygen release from an ACC-CP microgel in a neutral cell culture medium was suppressed because incorporation of CP in the ACC suppressed the reaction with water. Strikingly, stimuli to dissolve ACC such as a weak acidic conditions triggered the oxygen release from microgels loaded with ACC-CP, as the dissolution of CaCO₃ allows CP to react. Taken together, applications of this new class of biomaterials for tissue engineering are greatly anticipated. In addition, the developed microfluidic system can be used for a variety of oxygen-releasing microgels by changing the substrates of the hydrogel network.