A positron emission tomography approach to visualize flow perfusion in hollow-fiber membrane bioreactors

Abstract

Despite the success of hollow-fiber membrane bioreactors in tissue engineering, few evaluations of steady- and pulsatile-flow perfusion through these bioreactors have been made. Such evaluations are vital to the optimization of bioreactor culture conditions. In this study, positron emission tomography (PET) was proposed and used to visualize steady- and pulsatile-flow perfusion in hollow-fiber membrane bioreactors for tissue-engineering applications. PET is a noninvasive method that allows measuring the spatial distribution of a radioactive tracer by detecting its activity within porous scaffolds. A radioactive tracer, 18-fluoro-deoxy-glucose ((18)FDG), was injected into a fluid circuit having a hollow-fiber membrane bioreactor with gel-devoid or gel-filled extracapillary space. Dynamic PET scans of the inlet section were acquired and followed by volumetric PET scans of the whole bioreactor. Results were used to reconstruct dynamic and volumetric two- and three-dimensional images. Pulsatile inlet flow improved the uniformity of perfusion flow within the bioreactor in comparison to the steady inlet flow. Pulsatile flow also reduced the accumulation of radioactive tracer for both gel-devoid and gel-filled bioreactors compared to the steady flow. The stability of the radioactive tracer for both conditions was evaluated. The potential of the PET approach was demonstrated by the quantification of the imaging results for steady- and pulsatile-flow perfusions that can be used for the development of bioreactors for tissue-engineering applications.