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Updated: Jan 12, 2026

Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
Comparison of Serum Matrix Metalloproteinase-9 Levels in Diabetic and Non-diabetic Chronic Wounds
Jenny Joseph1, Alakhananda Chandranaath2, Joel Louis3
1Internal Medicine, Norwalk Hospital, Norwalk, USA.
Background:
Wound healing relies on a balance between extracellular matrix remodelling by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Among all the MMPs, elevated MMP-9 levels are implicated in chronic wounds including diabetic ulcers, making it a potential biomarker to predict wound healing. This in turn can help determine the need for aggressive wound care management. However, most studies used invasive sampling methods like wound fluid or tissue biopsy limiting clinical implementation. Hence, this study assessed the correlation between serum levels of MMP-9 in diabetic and non-diabetic chronic wounds to explore if non-invasive methods could be used to predict healing in diabetic chronic wounds.
Objective:
This study aimed to compare serum MMP-9 levels in diabetic vs. non-diabetic chronic wounds, assess correlations with glycemic control (glycated hemoglobin (HbA1c)), and determine the potential of serum MMP-9 as a predictor of healing in diabetic chronic wounds.
Methods:
This was a cross-sectional study involving 40 patients (20 diabetics, 20 non-diabetics) with chronic wounds. Serum MMP-9 levels were measured from blood samples (avoiding invasive methods) using an enzyme-linked immunosorbent assay (ELISA). HbA1c levels were obtained for patients with diabetes mellitus. Statistical analysis compared means (t-test) and correlations (Pearson's).
Results:
Patients with diabetes mellitus had significantly higher serum MMP-9 (mean 21.22 ng/ml) in comparison to non-diabetics (17.35 ng/ml; p=0.0023). When compared to only 5% (one out of 20) of non-diabetics, about 75% (15 out of 20) of diabetics had MMP-9 greater than 20 ng/ml. However, no correlation was found between MMP-9 and HbA1c levels (p>0.05) among diabetic patients.
Conclusions:
Serum MMP-9 is elevated in diabetic chronic wounds, supporting its role as a non-invasive biomarker. Several studies have established wound fluid/tissue MMP-9 as a predictor of healing in diabetic ulcers, and this study suggests that serum MMP-9 levels could be used as a non-invasive biomarker in place of cumbersome methods. However, the lack of association of MMP-9 with HbA1c suggests glycemic control alone may not regulate MMP-9. Targeting MMP-9 inhibition (e.g., via microRNAs) could be a therapeutic strategy, warranting further research.
Insights
Serum matrix metalloproteinase-9 (MMP-9) is elevated in diabetic chronic wounds, suggesting it can serve as a non-invasive biomarker for predicting wound healing. This study indicates serum MMP-9 levels may replace invasive methods for assessing diabetic ulcer healing.
Area of Science:
- Biochemistry
- Molecular Biology
- Wound Healing Research
Background:
- Wound healing involves a balance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
- Elevated MMP-9 levels are linked to chronic wounds, particularly diabetic ulcers, making MMP-9 a potential predictive biomarker.
- Current methods for assessing MMP-9 in wounds are invasive, limiting clinical application.
Purpose of the Study:
- To compare serum MMP-9 levels in diabetic versus non-diabetic chronic wounds.
- To assess the correlation between serum MMP-9 and glycemic control (HbA1c) in diabetic patients.
- To determine the potential of serum MMP-9 as a non-invasive predictor of wound healing in diabetic chronic wounds.
Main Methods:
- A cross-sectional study involving 40 patients with chronic wounds (20 diabetic, 20 non-diabetic).
- Serum MMP-9 levels were quantified using enzyme-linked immunosorbent assay (ELISA) from blood samples.
- Glycated hemoglobin (HbA1c) levels were measured in diabetic patients; statistical analyses included t-tests and Pearson correlations.
Main Results:
- Diabetic patients exhibited significantly higher serum MMP-9 levels (mean 21.22 ng/ml) compared to non-diabetic patients (17.35 ng/ml; p=0.0023).
- Approximately 75% of diabetic patients had MMP-9 levels above 20 ng/ml, versus only 5% of non-diabetic patients.
- No significant correlation was observed between serum MMP-9 levels and HbA1c in diabetic patients (p>0.05).
Conclusions:
- Elevated serum MMP-9 in diabetic chronic wounds supports its utility as a non-invasive biomarker.
- Serum MMP-9 may serve as a viable, less invasive alternative to wound fluid or tissue biopsy for predicting diabetic ulcer healing.
- The lack of correlation with HbA1c suggests that glycemic control alone may not fully regulate MMP-9 levels, highlighting potential therapeutic targets like microRNA inhibition.

