Computational modeling of chemo-bio-mechanical coupling: a systems-biology approach toward wound healing

Abstract

Wound healing is a synchronized cascade of chemical, biological, and mechanical phenomena, which act in concert to restore the damaged tissue. An imbalance between these events can induce painful scarring. Despite intense efforts to decipher the mechanisms of wound healing, the role of mechanics remains poorly understood. Here, we establish a computational systems biology model to identify the chemical, biological, and mechanical mechanisms of scar formation. First, we introduce the generic problem of coupled chemo-bio-mechanics. Then, we introduce the model problem of wound healing in terms of a particular chemical signal, inflammation, a particular biological cell type, fibroblasts, and a particular mechanical model, isotropic hyperelasticity. We explore the cross-talk between chemical, biological, and mechanical signals and show that all three fields have a significant impact on scar formation. Our model is the first step toward rigorous multiscale, multifield modeling in wound healing. Our formulation has the potential to improve effective wound management and optimize treatment on an individualized patient-specific basis.

Primal-mixed formulations for reaction–diffusion systems on deforming domains

“…We focus our attention in the numerical approximation of the chemical interaction between species concentrations and the response of the deformable medium where they react. Such a general framework is relevant to a wide range of applications going from molecular to macroscopic biological systems, and including, for instance, chemotaxis [52], organogenesis [41], bone remodelling [50,61], swelling of porous materials [38], cardiac electromechanics [31], tumor growth [10], force generation in skeletal muscle [15], wound healing [8], collagen network generation [34], tissue engineering [40], and many others.…”

Mathematical and computational modelling of skin biophysics: a review

“…In the electronic supplementary material section, plastic effects [80], softening and damage [81], recent coupled thermomechanical [82] as well as mechanobiological models for growth [64] will be presented. Other types of constitutive laws such as chemo-mechanobiological models of wound healing [12,[83][84][85] are beyond the scope of the present review.…”

“…In humans, the skin-which can be considered as a membrane-accounts for up to 16% of an adult's total body weight while covering an average surface area of about 1.6 m 2 [11]. As alluded to in Introduction section, the skin is a very complex biological system featuring a multitude of coupled physical processes acting in concert, or sequentially, as for instance, in the case of wound healing where a cascade of biochemical and mechanobiological events is triggered by an injury [12]. From the mechanical and material science point of view, the skin is primarily a multi-phasic and multi-scale structure which, as a result, encompasses a rich set of mechanical properties and constitutive behaviours [13,14].…”

A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues

“…These models focus on the underlying cellular and biochemical mechanisms to define and simulate dermal wound contraction [10][11][12] and angiogenesis [13][14][15] from a continuum-based approach. The inflammation and proliferation phases have also been modelled using a discrete or a hybrid discrete/continuum approach [16][17][18] and, more recently, a systems-biology multi-scale and multi-field approach has been proposed [19]. The reader is referred to the works by Tepole & Kuhl [20] and Valero et al [21] for a comprehensive review of mathematical and computational dermal wound healing models.…”