A Mechanobiology-Driven Computational–Experimental Framework for Investigating Cellular Remodeling During Wound Healing

Abstract

The process of cellular remodeling that occurs during wound healing is complex, in that it involves mechanobiological interactions between the fibroblast, extracellular matrix (ECM), and mechanical forces, and the current computational models do not always capture the multiscale mechanics with biological remodeling. Mechanobiology-informed computational–experimental approach is proposed to simulate wound healing dynamics, based on finite element analysis, cell–ECM adhesion kinetics, and remodeling of ECM. The framework successfully models the migration of fibroblasts, the generation of contractile stress, collagen deposition and the deformation of the tissue for different mechanical conditions, and it validates predictions against reference datasets for wound-healing. The simulation results show that the wound closure rate is 91.4%, followed by fibroblast density increased by 116.9%, probability of cell adhesion improvement by 74.5%, and the overall prediction accuracy of 92.8% (R² = 0.93; F1-score = 0.90) with progressive collagen remodeling. These results show the proposed framework is able to replicate mechanobiological remodeling and that it offers a viable computational framework for tissue regeneration and regenerative medicine research.