Abstract

The normal wound healing process is characterised by proteolytic events, whereas infection results in dysfunctional activations by endogenous and bacterial proteases. Peptides, downstream reporters of these proteolytic actions, could therefore serve as a promising tool for diagnosis of wounds. Using mass-spectrometry analyses, we here for the first time characterise the peptidome of human wound fluids. Sterile post-surgical wound fluids were found to contain a high degree of peptides in comparison to human plasma. Analyses of the peptidome from uninfected healing wounds and Staphylococcus aureus -infected wounds identify unique peptide patterns of various proteins, including coagulation and complement factors, proteases, and antiproteinases. Together, the work defines a workflow for analysis of peptides derived from wound fluids and demonstrates a proof-of-concept that such fluids can be used for analysis of qualitative differences of peptide patterns from larger patient cohorts, providing potential biomarkers for wound healing and infection.

Highlights

  • Wound infections after surgery and in relation to burns, as well as in non-healing wounds, are significant medical and societal problems (Sen et al, 2009)

  • Endogenous peptides serve as biomarkers of disease progression for several different diseases, and the here presented strategy and methodology identified the wound fluid peptidome as a source for assessment of wound fluid dynamics, as these fragments represent proteolytic events that are the result of basic physiological processes involving coagulation and complement activation, and additional proteolytic activities by endogenous and bacterial proteases

  • We have chosen to investigate the peptidome of wound fluids by a combination of lowmolecular-weight filtration, solid phase purification, and enrichment followed by mass spectrometry detection and database search

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Summary

Introduction

Wound infections after surgery and in relation to burns, as well as in non-healing wounds, are significant medical and societal problems (Sen et al, 2009). The costs of treating wounds are estimated to be over 3% of the total health care budgets of Western countries (Guest et al, 2017; Phillips et al, 2016) and these expenses are projected to grow with the increasing development of antimicrobial resistance, as well as ageing of the population and the rising incidence and prevalence of diseases such as obesity and diabetes (MedMarket Diligence, 2021) All these factors contribute to an increased risk for SSI, and to an increase in the incidence of non-healing wounds in elderly patients with circulatory insufficiencies.

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