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Title: The influence of microbial colonization on inflammatory versus pro-healing trajectories in combat extremity wounds

Journal Article · · Scientific Reports
 [1];  [1];  [2];  [1];  [1];  [3];  [1];  [1];  [4];  [3];  [3];  [3];  [5];  [5];  [5];  [5];  [6];  [3];  [6]
  1. Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD (United States)
  2. Q2 Solutions, Durham, NC (United States); Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD (United States)
  3. Uniformed Services University of the Health Sciences, Bethesda, MD (United States)
  4. Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
  5. Univ. of Pittsburgh, PA (United States)
  6. Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Walter Reed Army Institute of Research, Bethesda, MD (United States)
+ Show Author Affiliations

A combination of improved body armor, medical transportation, and treatment has led to the increased survival of warfighters from combat extremity injuries predominantly caused by blasts in modern conflicts. Despite advances, a high rate of complications such as wound infections, wound failure, amputations, and a decreased quality of life exist. To study the molecular underpinnings of wound failure, wound tissue biopsies from combat extremity injuries had RNA extracted and sequenced. Wounds were classified by colonization (colonized vs. non-colonized) and outcome (healed vs. failed) status. Differences in gene expression were investigated between timepoints at a gene level, and longitudinally by multi-gene networks, inferred proportions of immune cells, and expression of healing-related functions. Differences between wound outcomes in colonized wounds were more apparent than in non-colonized wounds. Colonized/healed wounds appeared able to mount an adaptive immune response to infection and progress beyond the inflammatory stage of healing, while colonized/failed wounds did not. Although, both colonized and non-colonized failed wounds showed increasing inferred immune and inflammatory programs, non-colonized/failed wounds progressed beyond the inflammatory stage, suggesting different mechanisms of failure dependent on colonization status. Overall, these data reveal gene expression profile differences in healing wounds that may be utilized to improve clinical treatment paradigms.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE; Defense Advanced Research Projects Agency (DARPA)
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
2471182
Journal Information:
Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 14; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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