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

Punyanuch Jindatanmanusan,Thirayost Nimmanon,Sivat Luanraksa,Pasra Arnutti,Tanit Boonsiri

doi:10.1155/2018/1631325

Punyanuch Jindatanmanusan, Thirayost Nimmanon + Show 3 more

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https://doi.org/10.1155/2018/1631325

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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.

Highlights

Wound healing is a complex process that can lead to chronic ulcers if any stage in this intricate series of events is interrupted [1]
All the wounds in the good healer group were completely healed before week 12, whereas none of the wounds in the poor healer group were healed throughout the 22-week study period
Because wounds were already healed in many good healers at week 8 and 12, only 4 samples were collected at week 8 and no collection was performed at week 12 in the good healer group

Summary

Introduction

Wound healing is a complex process that can lead to chronic ulcers if any stage in this intricate series of events is interrupted [1]. Like other types of chronic ulcers, which result from an exaggeration of the inflammatory phase, diabetic ulcers have a prolonged inflammatory phase along with significant increases in proinflammatory cytokines, proteases (MMPs), and neutrophil elastase [2] The increases in these protein levels are believed to be responsible for the increased extracellular matrix destruction observed in chronic wounds [3]. The excess of MMPs in chronic wounds is proposed to be contributory to poor wound healing through their action in breaking down of many extracellular matrix components and in inhibiting growth factors that are essential for tissue synthesis and wound healing [4, 5] These effects of high MMP levels result in poor wound healing efficiency. 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

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