Wound Fluid As A Biomarker: A Metabolomic Approach
Amitava Das, Subendu Sarkar, Joshua Johnson, Carly Polcyn, Scott Chaffee, Piya Das Ghatak, Suman Santra, Gayle M. Gordillo, Sashwati Roy, Chandan K. Sen
Comprehensive Wound Center, Center for Regenerative Medicine and Cell Based Therapies, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Background- The wound fluid bathing the wound tissue reflects the wound microenvironment and shapes the functional response of wound-related cells. Building on the scientific premise that metabolites in the wound microenvironment will shape the fate of the wound, we sought to identify biochemical markers in wound fluid that can delineate between wounds that will and will not heal.
Methods- Subjects (N=50) participating in the study were chronic wound patients seen at OSU Comprehensive Wound Center (CWC) clinics and have been undergoing NPWT (negative pressure wound therapy) as part of standard clinical care. Wound fluid and cells were derived from the NPWT dressing by lavaging the wound dressing with saline solution. Using different mass-spectrometry platforms, global biochemical profiles were compared in wound fluid samples from healing (>65% closure after 4 weeks) and non-healing (<20% closure after 4 weeks) wounds. Samples from each experimental group were measured and analyzed in an equivalent manner across the analytical platforms and analyzed after normalization based on measured protein values.
Results- Out of 622 metabolites screened, more than a third were found to be significantly lower in the non-healing group (p<0.05; n=25) indicative of blunted tissue metabolism in wounds not engaged in active tissue repair. Consistently, the non-healing cohort exhibited decreases in metabolites linked to amino acid and polyamine homeostasis, energy utilization and lipid homeostasis (p<0.05; n=25). Interestingly, in the wound fluid of non-healing group a 3-fold increase (p<0.05; n=25) in fibrinogen-derived peptide DSGEGDFXAEGGGVR levels was noted compared to the healing cohort. This metabolite is a proteolytic fragment of fibrinogen. How this metabolite contributes to the overall proteolytic activity of the chronic wound, which is known to be high, warrants further study.
Conclusion- This patient based study recognizes the value of wound fluid metabolite profile as a biomarker of wound outcome.
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