Mohammad Mehrian

Maximizing neotissue growth kinetics in a perfusion bioreactor: An in silico strategy using model reduction and Bayesian optimization

In regenerative medicine, computer models describing bioreactor processes can assist in designing optimal process conditions leading to robust and economically viable products. In this study, we started from a (3D) mechanistic model describing the growth of neotissue, comprised of cells, and extracellular matrix, in a perfusion bioreactor set‐up influenced by the scaffold geometry, flow‐induced shear stress, and a number of metabolic factors. Subsequently, we applied model reduction by reformulating the problem from a set of partial differential equations into a set of ordinary differential equations. Comparing the reduced model results to the mechanistic model results and to dedicated experimental results assesses the reduction step quality. The obtained homogenized model is 105 fold faster than the 3D version, allowing the application of rigorous optimization techniques. Bayesian optimization was applied to find the medium refreshment regime in terms of frequency and percentage of medium replaced that would maximize neotissue growth kinetics during 21 days of culture. The simulation results indicated that maximum neotissue growth will occur for a high frequency and medium replacement percentage, a finding that is corroborated by reports in the literature. This study demonstrates an in silico strategy for bioprocess optimization paying particular attention to the reduction of the associated computational cost.

Bayesian Multi-Objective Optimisation with Mixed Analytical and Black-Box Functions: Application to Tissue Engineering

Tissue engineering and regenerative medicine looks at improving or restoring biological tissue function in humans and animals. We consider optimising neotissue growth in a three-dimensional scaffold during dynamic perfusion bioreactor culture, in the context of bone tissue engineering. The goal is to choose design variables that optimise two conflicting objectives, first, maximising neotissue growth and, second, minimising operating cost. We make novel extensions to Bayesian multiobjective optimisation in the case of one analytical objective function and one black-box, i.e. simulation based and objective function. The analytical objective represents operating cost while the black-box neotissue growth objective comes from simulating a system of partial differential equations. The resulting multiobjective optimisation method determines the tradeoff between neotissue growth and operating cost. Our method exhibits better data efficiency than genetic algorithms, i.e. the most common approach in the literature, on both the tissue engineering example and standard test functions. The multiobjective optimisation method applies to real-world problems combining black-box models with easy-to-quantify objectives such as cost.

Bayesian Multi-Objective Optimisation of Neotissue Growth in a Perfusion Bioreactor Set-up

Abstract We consider optimising bone neotissue growth in a 3D scaffold during dynamic perfusion bioreactor culture. The goal is to choose design variables by optimising two conflicting objectives: (i) maximising neotissue growth and (ii) minimising operating cost. Our contribution is a novel extension of Bayesian multi-objective optimisation to the case of one black-box (neotissue growth) and one analytical (operating cost) objective function, that helps determine, within a reasonable amount of time, what design variables best manage the trade-off between neotissue growth and operating cost. Our method is tested against and outperforms the most common approach in literature, genetic algorithms, and shows its important real-world applicability to problems that combine black-box models with easy-to-quantify objectives like cost.