TY - JOUR

T1 - Arterial tissues and their inflammatory response to collagen damage

T2 - A continuum in silico model coupling nonlinear mechanics, molecular pathways, and cell behavior

AU - Gierig, Meike

AU - Wriggers, Peter

AU - Marino, Michele

N1 - 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.

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

KW - Damage-induced growth

KW - Homogenized constrained mixtures

KW - Inflammatory response

KW - Mechanobiology of healing

KW - Soft biological tissues

UR - http://www.scopus.com/inward/record.url?scp=85151434136&partnerID=8YFLogxK

U2 - 10.1016/j.compbiomed.2023.106811

DO - 10.1016/j.compbiomed.2023.106811

M3 - Article

VL - 158

JO - Computers in biology and medicine

JF - Computers in biology and medicine

SN - 0010-4825

M1 - 106811

ER -