Collagen/oxidized regenerated cellulose (ORC)/silver therapy has been designed to facilitate wound healing by normalizing the microenvironment and correcting biochemical imbalances in chronic wounds. The aim of this study was to compare collagen/ORC/silver therapy to control (standard treatment). Patients with diabetic foot ulcers were randomized to either collagen/ORC/silver (24) or control treatment (15). Wound area measurements and wound fluid samples were taken weekly. Protease levels were measured in wound fluid samples to investigate differences between responders (≥50% reduction in wound area by week 4) and nonresponders (<50% reduction in wound area by week 4). There were significantly more responders in the collagen/ORC/silver group compared with the control group (79% vs. 43%, p = 0.035). There were significantly fewer withdrawals from the study because of infection in the collagen/ORC/silver group compared with the control group (0% vs. 31%, p = 0.012). The sum of matrix metalloproteinase-9 and elastase concentration was higher in nonresponders compared with responders at baseline (p = 0.0705) and week 4 (p = 0.012). The results suggest that collagen/ORC/silver normalizes the wound microenvironment and protects against infection, resulting in improved wound healing. It was also demonstrated that measuring a combination of proteases may be a more relevant prognostic healing marker than any individual protease alone.
It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil-derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples (n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2-4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies.
Although the results were not significant, there was a trend toward faster healing in the intervention group. The results of this study indicate that collagen/oxidized regenerated cellulose/silver is a suitable and safe adjunctive intervention for use with SOC to manage VLUs.
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