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.

Keywords::

• wound healing
• systems biology
• chemo-bio-mechanics
• finite elements
• multiscale

Conflict of interest disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Consejo Nacional de Ciencia y Tecnologia CONACyT Fellowship and the Stanford Graduate Fellowship to Adrián Buganza Tepole and by the National Science Foundation CAREER award CMMI 0952021 and INSPIRE award 1233054 and the National Institutes of Health grant [grant number U01 HL119578] to Ellen Kuhl.