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.

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