Nutrient transport in bioreactors for bone tissue growth: Why do hollow fibre membrane bioreactors work?

One of the main aims of bone tissue engineering is to produce three-dimensional soft bone tissue constructs of acceptable clinical size and shape in bioreactors. The tissue constructs have been proposed as possible replacements for diseased or dysfunctional bones in the human body through surgical transplantations. However, because of certain restrictions to the design and operation of the bioreactors, the size of the tissue constructs attained are currently below clinical standards. We believe that understanding the fluid flow and nutrient transport behaviour in the bioreactors is critical in achieving clinically viable constructs. Nevertheless, characterization of transport behaviour in these bioreactors is not trivial. As they are very small in size and operate under stringent conditions, in-situ measurements of nutrients are almost impossible. This issue has been somewhat resolved using computational modelling in previous studies. However, there is still a lack of certainty on the suitability of bioreactors. To address this issue we systematically compare the suitability of three bioreactors for growing bone tissues using mathematical modelling tools. We show how nutrient transport may be improved in these bioreactors by varying the operating conditions and suggest which bioreactor may be best suited for operating at high cell densities in order to achieve soft bone tissues of clinical size. The governing equations defined in our mathematical frameworks are solved through finite element method. The results show that the hollow fibre membrane bioreactor (HFMB) is able to maintain higher nutrient concentration during operation at high cell densities compared to the other two bioreactors, namely suspended tube and confined profusion type bioreactor. Our results show that by varying the operating conditions nutrient transport may be enhanced and the nutrient gradient can be substantially reduced. These are consistent with previous claims suggesting that the HFMB is suited for bone tissue growth at high cell densities.