Computational modeling of cell motility and clusters formation in enzyme-sensitive hydrogels

In this paper, we propose an extension of a previous model of cell motility in tissue engineering applications recently developed by the authors. Achieving large-scale production of neo-tissue through biofabrication technologies remains challenging owing to the need of thoroughly optimizing all the relevant process variables, a task hardly attainable through solely trial and error approaches. Therefore, the present work is intended to provide a valid and effective computational-based support for neo-tissue formation, with a specific focus on the preliminary phase of such process, in which cells move through a polymeric scaffold (hydrogel) and then compact into clusters. Cell motility is modeled by resorting to the phase-field method, and by incorporating diffusion of nutrients from the external culture bath as well as the expression by cells of chemoattractant substances that bias the random path they otherwise would follow. The previous model has been enriched by additionally encompassing the secretion of enzymes by cells that cleave the crosslinks between the hydrogel polymer chains. As such, in the present model hydrogel degradation exhibits spatio-temporal variations in its chemo-physical properties related to the local amount of enzymes, which deeply affects cell motility. Numerical results showcase the pivotal importance of the cells micro-environment properties for their crawling in hydrogel scaffolds, opening towards the development of a predictive computational-aided optimization tool for neo-tissue growth in bioprinted scaffolds.