Controlling oxygen release from hollow microparticles for prolonged cell survival under hypoxic environment

The survival of cells in the 3D scaffold until the ingrowth of blood vessels is one of the most important challenges in tissue engineering for producing a clinically relevant volume of tissue. In this study, perfluorooctane emulsion (oxygen carrier)-loaded hollow microparticles (PFO-HPs) were prepared as a scaffolding system which can allow timely release of oxygen to cells adhered on the HPs to prevent cell necrosis in a hypoxic environment (inherently created in tissue engineered 3D constructs) until new blood vessels are formed in the 3D cell construct, and thus may produce appropriate tissues/organs with a clinically relevant volume. In the in vitro cell culture and the in vivo animal study, it was observed that the cells initially seeded on the PFO-HPs remained alive for approximately 10 days in a hypoxic environment (in vitro), and the cells were also found throughout the implanted whole matrix without a necrotic center until the infiltration of blood vessels (at 14 days after implantation; in vivo), probably due to the sufficient release of oxygen from the PFO-HPs for an adequate time period. Based on these results, the cell-based PFO-HPs can be a promising system to produce a clinically applicable large tissue mass.