Agent-based modeling of wound healing: Examples for basic and translational research

Wounds either can arise from a disease process or are surgically created as part of therapy. The healing of damaged tissue is a fundamental biological process, involving a complex set of cellular and molecular components acting within a specific spatial context. Impairment or aberration of the wound healing process is a considerable source of morbidity and mortality, likely only to increase in clinical significance given an aging population. Despite considerable advances in the mechanistic knowledge of wound healing, as with all complex biological processes converting that knowledge into effective therapeutics is a substantial translational challenge. As a result, wound healing has been a major focus in the field of Translational Systems Biology, and, in particular, been a subject of agent-based mechanistic computational modeling. The intuitive mapping between biological knowledge and the rules in an agent-based model (ABM), the ability of an ABM to readily represent stochastic processes, and the inherent spatial representation capability of an ABM all facilitate the utilization of this method in the practice of Translational Systems Biology. Presented herein are a series of ABMs of wound healing that demonstrate the translational potential and utility of this methodology in advancing the rational development of wound healing therapeutics.