Bioprocess Optimisation for Stem Cell Tissue Engineering

bioreactor_picturesThe Imperial Biological Systems Engineering Laboratory  recently developed a novel, biomimetic, cost-effective three-dimensional hollow fibre bioreactor for growing healthy red blood cells ex vivo (Panoskaltsis et al., 2012). This bioreactor recapitulates architectural and functional properties of erythrocyte formation and thereby reduces the need for expensive growth factors by more than an order of magnitude. Individual experiments to empirically improve the bioreactor are intensive, so we propose global superstructure optimisation for bioreactor design. Misener et al. (2014) integrate topological design choices with operating conditions. Design choices include: number of parallelised bioreactors; number and type of hollow fibres; size and aspect ratio. Operating conditions are: feed concentrations; flowrate through the reactor. We quantitatively demonstrate, for the first time, the potential for ex vivo red blood cell production to compete openly against the transfusion market for rare blood.

Robust Optimisation Under Uncertainty

In stem cell biomanufacturing, an optimal but non-robust design may be sensitive to uncertainty. To see the possible trouble with parameter uncertainty, consider the figure at left (see full-sized image here). Misener et al. (2017) use robust optimisation to find the best solution inoculated against parameter uncertainty. We quantify the parameter uncertainty using image and material analysis tools (Allenby et al., 2017, Panoskaltsis et al., 2012).

The blood-producing bioreactor is also subject to model uncertainty, e.g. there are different possible mathematical representations for the transformation from progenitor to red blood cells. For the blood-producing bioreactor, we reformulated the model uncertainty into parameter uncertainty and incorporated it into the robust optimisation problem.

The figure at right summarises the Misener et al. (2017) recipe for stem cell biomanfacturing under uncertainty (see full-sized image here).

Extensions to Neotissue Growth Kinetics

Several of the optimisation techniques we developed for the blood-producing bioreactor are also relevant for other areas of tissue engineering. PhD student Simon Olofsson and I collaborated with the group of Professor Liesbet Geris to optimise bone neotissue growth in a perfusion bioreactor (Mehrian et al., 2017).


Poster for a General, Technically-Educated Audience


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