A methodology combining reinforcement learning and simulation to optimize the in silico culture of epithelial sheets

Tissue Engineering (TE) and Regenerative Medicine (RM) aim to replicate and replace tissues for curing disease. However, full tissue integration and homeostasis are still far from reach. Biofabrication is an emerging field that identifies the processes required for generating biologically functional products with the desired structural organization and functionality and can potentially revolutionize the regenerative medicine domain, which aims to use patients’ cells to restore the structure and function of damaged tissues and organs. However, biofabrication still has limitations in the quality of processes and products. Biofabrication processes are often improved empirically, but this is slow, costly, and provides partial results. Computational approaches can tap into biofabrication underused potential, supporting analysis, modelling, design, and optimization of biofabrication processes, speeding up their improvement towards a higher quality of products and subsequent higher clinical relevance. This work proposes a reinforcement learning-based computational design space exploration methodology to generate optimal in-silico protocols for the simulated fabrication of epithelial sheets. The optimization strategy relies on a Deep Reinforcement Learning (DRL) algorithm, the Advantage-Actor Critic, which relies on a neural network model for learning. In contrast, simulations rely on the PalaCell2D simulation framework. Validation demonstrates the proposed approach on two protocol generation targets: maximizing the final number of obtained cells and optimizing the spatial organization of the cell aggregate.