Bifurcation in the healing or fibrotic response in a network model of fibrosis: role of the initial injury structure.

Results demonstrate that fibrosis is strongly associated with increased initial clustering of injured springs, reduced intercluster distances, and the presence of critical stiffening sites, or hotspots, that act as bifurcation points for disease progression. Furthermore, we show that selectively modifying the stiffness of pivotal network regions at the time of injury can shift the network's trajectory from fibrosis to healing, highlighting potential intervention targets. These findings suggest that the network structure of tissue injury may serve as a predictive marker for fibrosis susceptibility and provide a mechanistic basis for understanding the nonlinear progression of PF.