Abstract

This study presents a continuum multiphysics approach to mathematically and physically describe the behavior of living systems, capturing the interaction between cells and extracellular matrix (ECM) to simulate tissue-level responses such as wound healing and tissue reconfiguration. As most processes in living systems involve highly nonlinear multiphysical phenomena, this study aims to provide insight into the locally-averaged details of these processes. To achieve this, experimental observations and physical concepts are utilized to motivate theoretical formulations in a nonlinear solid mechanics framework. This work utilizes an array of mixed finite element formulations, where special discretization techniques and numerical analysis algorithms are discussed to simulate these complex systems accurately in a robust manner. The proposed models are validated through experimental results that capture the changes in tissue construct shape and cell concentration for wounded and intact microtissues, enabling the interpretation of experimental data. One of the main points of this study is to understand the collective response of cells during remodeling in the context of cell-ECM interactions and its effect on tissue morphology. This continuum multiphysics framework provides valuable insights into cell-ECM interactions that can be extended to development and cancer, tissue engineering, and regenerative medicine, and can aid in developing novel regenerative therapies.