Optimization of Culture Conditions in a Bioreactor for Vascular Tissue Engineering Using a Mathematical Model of Vascular Growth and Remodeling

Abstract

Functional vascular tissue engineering (VTE) aims to grow tissue engineered blood vessels in vitro. Bioreactors maintain the complex physical, mechanical and biochemical conditions for the optimal culture of vascular tissues. However, the growth and remodeling processes that take place in vascular constructs during maturation in a bioreactor are difficult both to understand and to optimize because many factors and interactions influence the vascular regeneration. In this work, this problem was approached from the point of view of process control: first, genetic programing (GP) was used to search a growth and remodeling model from experimental data harvested during culture of vascular constructs; second, Markov decision process (MDP) was used to select optimal culture parameters in the bioreactor. To validate this approach, this new controller based on GP and MDP was confronted with a highly non-linear mathematical model of growth and remodeling in VTE. The conducted numerical simulations showed the ability of the controller to maximize growth rate and to generate hypotheses about the processes in bioreactors. Insights from this approach suggest a new interesting way to model the regeneration of a tissue engineered artery by considering multiple stages to the maturation of vascular tissues.