Spatio-temporal mathematical model describing the interplay between biomechanics and cell kinetics during fibrotic scar formation

Liver fibrosis is characterized by the accumulation of overexpressed extracellular matrix (ECM) proteins as a result of exposure of tissue to repeated damage. There are distinct patterns of fibrosis such as collagen septa (from tissue sections called “fibrotic walls”) connecting two central veins due to toxic injury. In the past decade, some computational models using either rule-based models 2D or partial differential equations of liver fibrosis to study the cellular and molecular mechanisms. Within a 3D single-cell-based model resolving tissue microarchitecture, we now incorporate the collagen fiber mechanics to address fibrosis formation. The same model approach already simulated regeneration after acute liver damage hence fibrosis formation is a further step towards a digital liver twin. The pattern-characterizing parameters in this study were obtained through image analysis of images from animal experiments that were compared to human histopathology. We explored alternative model mechanisms and parameters for a detailed in silico study of possible mechanism on the formation of characteristic fibrotic walls in liver fibrosis.

 

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Publication History

Article published online:
18 January 2023