Arterial tissues and their inflammatory response to collagen damage

A continuum in silico model coupling nonlinear mechanics, molecular pathways, and cell behavior

authored by: Meike Gierig, Peter Wriggers, Michele Marino
Abstract: Damage in soft biological tissues causes an inflammatory reaction that initiates a chain of events to repair the tissue. This work presents a continuum model and its in silico implementation that describe the cascade of mechanisms leading to tissue healing, coupling mechanical as well as chemo-biological processes. The mechanics is described by means of a Lagrangian nonlinear continuum mechanics framework and follows the homogenized constrained mixtures theory. Plastic-like damage, growth and remodeling as well as homeostasis are taken into account. The chemo-biological pathways account for two molecular and four cellular species, and are activated by damage of collagen molecules in fibers. To consider proliferation, differentiation, diffusion and chemotaxis of species, diffusion–advection–reaction equations are employed. To the best of authors’ knowledge, the proposed model combines for the first time such high number of chemo-mechano-biological mechanisms in a consistent continuum biomechanical framework. The resulting set of coupled differential equations describe balance of linear momentum, evolution of kinematic variables as well as mass balance equations. They are discretized in time according to a backward Euler finite difference scheme, and in space through a finite element Galerkin discretization. The features of the model are firstly demonstrated presenting the species dynamics and highlighting the influence of damage intensities on the growth outcome. In terms of a biaxial test, the chemo-mechano-biological coupling and the model's applicability to reproduce normal as well as pathological healing are shown. A last numerical example underlines the model's applicability to complex loading scenarios and inhomogeneous damage distributions. Concluding, the present work contributes towards comprehensive in silico models in biomechanics and mechanobiology.
Organisation(s): Institute of Continuum Mechanics
Type: Article
Journal: Computers in biology and medicine
Volume: 158
ISSN: 0010-4825
Publication date: 05.2023
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Computer Science Applications, Health Informatics
Electronic version(s): https://doi.org/10.1016/j.compbiomed.2023.106811 (Access: Closed)
: Details in the research portal "Research@Leibniz University"

BibTeX

@article{dcecc5fef9d44f14b7e1680a1383b13a,
title = "Arterial tissues and their inflammatory response to collagen damage: A continuum in silico model coupling nonlinear mechanics, molecular pathways, and cell behavior",
abstract = "Damage in soft biological tissues causes an inflammatory reaction that initiates a chain of events to repair the tissue. This work presents a continuum model and its in silico implementation that describe the cascade of mechanisms leading to tissue healing, coupling mechanical as well as chemo-biological processes. The mechanics is described by means of a Lagrangian nonlinear continuum mechanics framework and follows the homogenized constrained mixtures theory. Plastic-like damage, growth and remodeling as well as homeostasis are taken into account. The chemo-biological pathways account for two molecular and four cellular species, and are activated by damage of collagen molecules in fibers. To consider proliferation, differentiation, diffusion and chemotaxis of species, diffusion–advection–reaction equations are employed. To the best of authors{\textquoteright} knowledge, the proposed model combines for the first time such high number of chemo-mechano-biological mechanisms in a consistent continuum biomechanical framework. The resulting set of coupled differential equations describe balance of linear momentum, evolution of kinematic variables as well as mass balance equations. They are discretized in time according to a backward Euler finite difference scheme, and in space through a finite element Galerkin discretization. The features of the model are firstly demonstrated presenting the species dynamics and highlighting the influence of damage intensities on the growth outcome. In terms of a biaxial test, the chemo-mechano-biological coupling and the model's applicability to reproduce normal as well as pathological healing are shown. A last numerical example underlines the model's applicability to complex loading scenarios and inhomogeneous damage distributions. Concluding, the present work contributes towards comprehensive in silico models in biomechanics and mechanobiology.",
keywords = "Damage-induced growth, Homogenized constrained mixtures, Inflammatory response, Mechanobiology of healing, Soft biological tissues",
author = "Meike Gierig and Peter Wriggers and Michele Marino",
note = "Funding Information: M. Marino gratefully acknowledges funding from the Italian Ministry of Education, University and Research MIUR (Programma per Giovani Ricercatori - anno 2017 Rita Levi Montalcini) and of Regione Lazio, Italy (POR FESR LAZIO 2014; Progetti di Gruppi di Ricerca 2020; project: BIOPMEAT, n. A0375-2020-36756). P. Wriggers gratefully acknowledges the support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - SFB/TRR-298-SIIRI - Project-ID 426335750.",
year = "2023",
month = may,
doi = "10.1016/j.compbiomed.2023.106811",
language = "English",
volume = "158",
journal = "Computers in biology and medicine",
issn = "0010-4825",
publisher = "Elsevier Ltd.",
}