(WHS-K1.01) What is Slough? Defining the proteomic and microbial composition of wound slough and its implications for wound healing.
Thursday, May 16, 2024
9:15 AM – 10:15 AM East Coast USA Time
Intro: Slough is a well-known feature of chronic wounds. However, the tissue and microbial composition of wound slough are not well defined. Clinically, it’s difficult to define what is normal slough and identify wounds likely to heal versus deteriorate.
Aims: To determine the proteomic and microbiologic components of slough and their associations with wound healing.
Methods: 23 subjects with chronic wounds and visible slough were enrolled. Etiologies included venous stasis ulcers, post-surgical site infections, and pressure ulcers. Patient co-morbidities and wound healing outcome 3-months post sample collection were recorded. Debrided slough was analyzed microscopically, through untargeted proteomics, and high-throughput bacterial 16S-rRNA gene sequencing.
Results: Wound age ranged from 6 weeks to 15 years. Microscopic imaging revealed slough to be amorphous in structure. 16S-profiling found slough microbial communities associate with wound etiology and location on the body (both PERMANOVA p<0.01). Across all subjects, slough predominantly consisted of proteins involved in skin structure and formation, blood-clot formation, and immune processes. To predict variables associated with wound healing, protein, microbial, and clinical datasets were integrated into a supervised partial least squares-discriminant analysis. This analysis found wounds that healed 3-months after sample collection were enriched for proteins involved in skin barrier development (eg cornifin B) and negative regulation of immune responses (eg cystatin F). Differential enrichment of these proteins in healed wounds compared to those that deteriorated was confirmed via DEqMS (all absolute Log2(fold change)>1.5 and p<0.01). Wounds that deteriorated over time started off with a higher baseline Bates-Jensen Wound Assessment score and were enriched for anerobic bacteria (eg Fingoldia & Peptoniphilus) and chronic inflammatory proteins (eg activator protein-1, vasodilator-stimulated phosphoprotein, & complement factor H; all absolute Log2(fold change)>1.5 and p<0.01).
Discussion: Slough is an underutilized reservoir for potential biomarkers of wound healing. This is the first study to integrate clinical, microbiome, and proteomic data to systematically characterize wound slough and integrate it into a single assessment to predict wound healing outcome. Collectively, our findings underscore how slough components can help identify wounds at risk of continued impaired healing. Future studies aim to explore these predicted biomarkers in a larger cohort. Development of a comprehensive patient-centered assessment will lead to more effective identification of patients’ wounds that may benefit from triage into specialty care and ultimately reduce the healthcare, financial, and personal burden of living with a chronic wound.