Wound Fluid Matrix Metalloproteinase-9 as a Potential Predictive Marker for the Poor Healing Outcome in Diabetic Foot Ulcers

Abstract

Background and Objective Evidence for the roles of matrix metalloproteinases-9 (MMP-9) in the healing process of diabetic foot ulcers has remained unclear. We therefore aimed to demonstrate the relationship of MMP-9 with the wound healing process and determine its potential usefulness in predicting the wound healing outcome. Methods Twenty-two patients with diabetic foot ulcer were recruited. The wound size was determined, and the wound fluid was collected for the measurement of MMP-9 levels using an ELISA during the 12-week follow-up period regularly. The patients were categorized as good healers and poor healers when the wound area reduction was ≥ 50% and < 50% at week 4 when compared to the initial wound size at week 0. Results Median wound fluid MMP-9 levels in the poor healer group were shown to be significantly higher than those in the good healer group (1.03 pg/µg protein vs. 0.06 pg/µg protein, p = 0.001), and the levels fluctuated throughout the 12-week follow-up period. In contrast to the poor healer group, the MMP-9 levels were demonstrated to be constantly low throughout the follow-up period in the good healer group. ROC analysis showed that the MMP-9 level of 0.38 pg/µg protein was able to predict the wound healing outcome with the sensitivity of 81.8%, the specificity of 64.6%, and the area under the curve of 0.901 (CI 0.78-1.03, p = 0.001). Conclusion These findings suggested that determination of wound fluid MMP-9 levels might become a promising biomarker predicting wound healing outcomes and a novel potential therapeutic target for diabetic foot ulcers.

Aberrant recruitment of leukocytes defines poor wound healing in patients with recessive dystrophic epidermolysis bullosa

“…Wound repair results from a highly complex interaction of cellular and biochemical events. To date, many investigations described proteins and signaling molecules that contribute to the disordered healing, as for example in diabetic foot ulcers (DFU) [9,10], yet, these molecular networks remain poorly defined in RDEB wounds. Considering a known contribution of matrix metalloproteinases (MMPs) to chronic wound pathogenesis [11], we assessed MMP2 and MMP9 in a low molecular weight (LMW) fraction.…”

Bioengineered Platforms for Chronic Wound Infection Studies: How Can We Make Them More Human-Relevant?

“…Chronic wound fluid is an important factor in the wound milieu (Trengove et al, 1996;Cutting, 2003;Widgerow, 2011;Manuela et al, 2017), reflecting the processes and functions that contribute to and perpetuate the chronic wound state. In addition to a unique signature of proteins, growth factors and proinflammatory cytokines, chronic wound fluid is known to contain high levels of matrix metalloproteinases (MMPs), which impact a range of functions related to the chronic wound state (Wysocki et al, 1993;Jindatanmanusan et al, 2018). For example, increased levels of the enzymes MMP-2 and MMP-9 have been found to correlate with the severity of chronic wounds (Grzela et al, 2016).…”

Characterization of Dermal Stem Cells of Diabetic Patients

“…In diabetic dermis, the expression of MMP9 gene was upregulated, while their inhibitor TIMP1 was indifferently expressed. Previous studies on DFUs have reported that a high concentration of MMP9 in wound liquid and a high ratio of MMP9 to TIMP1 are related to poor wound healing [28,29]. A 5-fold increase in the expression of MMP1 was also detected in diabetic dermis.…”