Translational systems biology: introduction of an engineering approach to the pathophysiology of the burn patient

Abstract

The pathophysiology of the burn patient manifests the full spectrum of the complexity of the inflammatory response. In the acute phase, inflammation may have negative effects via capillary leak, the propagation of inhalation injury, and development of multiple organ failure. Attempts to mediate these processes remain a central subject of burn care research. Conversely, inflammation is a necessary prologue and component in the later stage processes of wound healing. Despite the volume of information concerning the cellular and molecular processes involved in inflammation, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective clinical therapeutic regimens. Translational systems biology (TSB) is the application of dynamic mathematical modeling and certain engineering principles to biological systems to integrate mechanism with phenomenon and, importantly, to revise clinical practice. This study will review the existing applications of TSB in the areas of inflammation and wound healing, relate them to specific areas of interest to the burn community, and present an integrated framework that links TSB with traditional burn research.

Figure 1

Relationship between Translational Systems Biology and Classical Systems Biology: Biological Organization has a nested, hierarchical structure. Each hierarchy, however, is bounded to some epistemological degree due to the principles of biocomplexity. Classical systems biology generally focuses on the characterization and description of mechanisms of cellular control with an emphasis on genetic regulation and intracellular signaling. Translational systems biology attempts to use the knowledge generated at the subcellular level and extrapolates that knowledge to the type of systemic behavior seen in the clinical setting. These two approaches are complementary and generally intersect at the level of cellular and tissue behavior.