Modeling the effects of systemic mediators on the inflammatory phase of wound healing

J Theor Biol. 2015 Feb 21:367:86-99. doi: 10.1016/j.jtbi.2014.11.008. Epub 2014 Nov 20.


The normal wound healing response is characterized by a progression from clot formation, to an inflammatory phase, to a repair phase, and finally, to remodeling. In many chronic wounds there is an extended inflammatory phase that stops this progression. In order to understand the inflammatory phase in more detail, we developed an ordinary differential equation model that accounts for two systemic mediators that are known to modulate this phase, estrogen (a protective hormone during wound healing) and cortisol (a hormone elevated after trauma that slows healing). This model describes the interactions in the wound between wound debris, pathogens, neutrophils and macrophages and the modulation of these interactions by estrogen and cortisol. A collection of parameter sets, which qualitatively match published data on the dynamics of wound healing, was chosen using Latin Hypercube Sampling. This collection of parameter sets represents normal healing in the population as a whole better than one single parameter set. Including the effects of estrogen and cortisol is a necessary step to creating a patient specific model that accounts for gender and trauma. Utilization of math modeling techniques to better understand the wound healing inflammatory phase could lead to new therapeutic strategies for the treatment of chronic wounds. This inflammatory phase model will later become the inflammatory subsystem of our full wound healing model, which includes fibroblast activity, collagen accumulation and remodeling.

Keywords: Cortisol; Estrogen; Macrophages; Neutrophils; ODE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Estrogens / pharmacology
  • Humans
  • Hydrocortisone / pharmacology
  • Immunity / drug effects
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism*
  • Kinetics
  • Macrophage Activation / drug effects
  • Models, Biological*
  • Neutrophils / drug effects
  • Reproducibility of Results
  • Time Factors
  • Wound Healing* / drug effects


  • Estrogens
  • Inflammation Mediators
  • Hydrocortisone