28 April 2025
Authored by : Taylor E. Hinchliffe, Co-Authors: Dr. Caroline N. Jones and Dr. Roger F. Malina
1.Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080 USA.
2.Department of Biomedical Engineering, UT Southwestern Medical Center, Dallas, TX 75390 USA.
3.School of Arts, Technology and Emerging Communications, University of Texas at Dallas, Richardson, TX 75080 USA.
Sepsis is a complex immune disorder that ultimately involves a failure of the immune system to resolve off-target inflammation as it attempts to contain a pathogen, resulting in increasing degrees of tissue damage that can lead to organ failure and death [1]. Although sepsis research often involves reductionist approaches that look for key biomarkers, such as altered neutrophil behavior and form [2], or elevated blood concentrations of cytokines and other inflammatory molecules [3, 4], clinical manifestations of sepsis spanning hypotension [5] to acute respiratory distress syndrome (ARDS) [6] ultimately involve a variety of interactions,
feedback loops, behavioral and functional changes, and altered populations of molecular and cellular subsystem components across multiple space and time scales within the body. Therefore, the resolution of sepsis requires nudging a variety of systems back to homeostasis, and understanding its complexity to improve treatment outcomes would thus benefit from a version of systems science that recognizes and integrates differences across multiple system scales while analyzing complex system behaviors such as feedback loops, nonlinearity, irreducibility, criticality, interdependence, and simultaneous bottom-up and top-down causality. Such indicates that the study of sepsis could benefit from the lens of a specific subset of complex systems science — that of emergence — because it arises from a variety of interacting molecular and cellular subsystems with little to no resemblance in form and function to the greater organ and organism systems they constitute. Therefore, we have combined expertise in translational sepsis
research [7] with that of the University of Texas at Dallas Center for Emergence Studies [8] to present sepsis through a novel lens.