Mathematical modelling of a liver hollow fibre bioreactor

A mathematical model has been developed to assist with the development ofa hollow fibre bioreactor (HFB) forhepatotoxicity testing of xenobiotics; specifically, to informthe HFBoperating set-up, interpret data from HFB outputsand aid in optimizingHFBdesign to mimic certain hepatic physiological conditions. Additionally,the mathematical model has been used to identify the key HFB and compound parameters that will affect xenobiotic clearance. The analysis of this model has produced novel results that allow the operating set-up to be calculated,and predictions of compound clearanceto begenerated.The mathematical modelpredictsthe inlet oxygen concentration and volumetric flow ratethat gives a physiological oxygen gradient in the HFB to mimic a liver sinusoid. It has also been used to predict the concentration gradients and clearanceof a test drug and paradigm hepatotoxin, paracetamol (APAP).The effect of altering theHFBdimensions and fibre propertieson APAP clearance under the condition of a physiological oxygen gradientis analysed.These theoretical predictions can be usedto design the most appropriateexperimental set upand data analysis toquantitatively compare the functionality of cell types that are cultured within the HFB to those in other systems