Increased Matrix Metalloproteinase-9 Predicts Poor Wound Healing in Diabetic Foot Ulcers

  1. Yu Liu, MD1,
  2. Danqing Min, PHD2,
  3. Thyra Bolton3,
  4. Vanessa Nubé3,
  5. Stephen M. Twigg, PHD, MD123,
  6. Dennis K. Yue, PHD, MD123 and
  7. Susan V. McLennan, PHD12
  1. 1Discipline of Medicine, University of Sydney, Sydney, Australia
  2. 2Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia
  3. 3Diabetes Centre, Royal Prince Alfred Hospital, Sydney, Australia
  1. Corresponding author: Susan McLennan, smclennan{at}


OBJECTIVE—We studied the relationships of diabetic ulcer wound fluid matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and transforming growth factor-ß1 (TGF-ß1) with wound healing rate.

RESEARCH DESIGN AND METHODS—The ulcers were cleansed to remove exudates, and wound fluids were collected for analysis of MMP-2 and -9, TIMP-1, and TGF-ß1.

RESULTS—At presentation, MMP-9 and the MMP-9–to–TIMP-1 ratio correlated inversely with the wound healing rate at 28 days (P < 0.001). MMP-9 and the MMP-9–to–TIMP-1 ratio were lower in the 23 patients who achieved complete healing at 12 weeks versus the 39 who did not. The pro–MMP-9 concentration was predictive of healing within 12 weeks. Addition of cutoffs for TIMP-1 (>480 pg/ml) and TGF-ß (>115 pg/ml) further improved its predictive power (area under the curve 0.94).

CONCLUSIONS—These findings suggest that a milieu with high MMP-9 may be indicative of inflammation and poor wound healing. Measurements of MMP-9, TIMP-1, and TGF-ß in wound fluid may help to identify ulcers at risk of poor healing.


  • Published ahead of print at on 3 October 2008.

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    • Accepted September 18, 2008.
    • Received April 21, 2008.
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  1. Diabetes Care vol. 32 no. 1 117-119
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