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Updated: Jun 23, 2026
Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
Mice that lack matrix metalloproteinase-9 display delayed wound healing associated with delayed reepithelization and
Themis R Kyriakides1, Drausin Wulsin, Eleni A Skokos
1Interdepartmental Program in Vascular Biology and Therapeutics and Department of Pathology, Yale University, New Haven, CT 06519, United States. themis.kyriakides@yale.edu
Abstract:
Matrix metalloproteinase- (MMP-9) is involved in processes that occur during cutaneous wound healing such as inflammation, matrix remodeling, and epithelialization, To investigate its role in healing, full thickness skin wounds were made in the dorsal region of MMP-9-null and control mice and harvested up to 14 days post wounding. Gross examination and histological and immunohistochemical analysis indicated delayed healing in MMP-9-null mice. Specifically, MMP-9-null wounds displayed compromised reepithelialization and reduced clearance of fibrin clots. In addition, they exhibited abnormal matrix deposition, as evidenced by the irregular alignment of immature collagen fibers. Despite the presence of matrix abnormalities, MMP-9-null wounds displayed normal tensile strength. Ultrastructural analysis of wounds revealed the presence of large collagen fibrils, some with irregular shape. Keratinocyte proliferation, inflammation, and angiogenesis were found to be normal in MMP-9-null wounds. In addition, VEGF levels were similar in control and MMP-9-null wound extracts. To investigate the importance of MMP-9 in wound reepithelialization we tested human and murine keratinocytes in a wound migration assay and found that antibody-based blockade of MMP-9 function or MMP-9 deficiency retarded migration. Collectively, our observations reveal defective healing in MMP-9-null mice and suggest that MMP-9 is required for normal progression of wound closure.
Insights
Matrix metalloproteinase-9 (MMP-9) is crucial for normal skin wound healing. MMP-9 deficiency in mice resulted in delayed healing, impaired reepithelialization, and abnormal matrix deposition.
Area of Science:
- Dermatology
- Molecular Biology
- Wound Healing Research
Background:
- Matrix metalloproteinase-9 (MMP-9) plays a role in cutaneous wound healing processes.
- Key processes include inflammation, matrix remodeling, and epithelialization.
Purpose of the Study:
- To investigate the specific role of MMP-9 in the progression of skin wound healing.
- To determine the impact of MMP-9 deficiency on various stages of the healing process.
Main Methods:
- Full thickness skin wounds were created in MMP-9-null and control mice.
- Wounds were analyzed macroscopically, histologically, and immunohistochemically up to 14 days post-wounding.
- Keratinocyte migration assays were performed using human and murine cells.
Main Results:
- MMP-9-null mice exhibited delayed wound healing with compromised reepithelialization and reduced fibrin clot clearance.
- Abnormal matrix deposition, characterized by irregular collagen alignment, was observed in MMP-9-null wounds.
- Keratinocyte proliferation, inflammation, angiogenesis, and VEGF levels were unaffected by MMP-9 deficiency, but keratinocyte migration was retarded.
Conclusions:
- MMP-9 is essential for the normal progression of cutaneous wound closure.
- MMP-9 deficiency leads to defective healing, primarily affecting reepithelialization and matrix remodeling.
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