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Updated: Feb 3, 2026
Murine Model of Wound Healing
Published on: May 28, 2013
The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice
James S Lee1, Avril A B Robertson2, Matthew A Cooper3
1UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Wooloongabba, QLD 4102, Australia. j.lee@uq.edu.au.
Abstract:
The incidence of chronic wounds is escalating, and the associated healing process is especially problematic in an aging population with increased morbidity. Targeting increased inflammation in chronic wounds is a promising but challenging therapeutic strategy. Indeed, inflammation and especially macrophages are required for wound healing. As the NLRP3 inflammasome has been implicated with various other inflammatory diseases, in this study, we used MCC950-a selective NLRP3 small molecule inhibitor-on murine models of both acute and chronic wounds. This molecule, while tested for other inflammatory conditions, has never been investigated to reduce topical inflammation driving chronic wounds. We found that there were no significant differences when the treatment was applied either topically or orally in wild-type C57Bl/6 mice and that it even impaired wound healing in obese mice. The treatment was also unable to improve re-epithelialisation or angiogenesis, which are both required for the closure of wounds. We are inclined to believe that MCC950 may inhibit the closure of chronic wounds and that it does not alter wound-associated macrophage polarisation.
Insights
Targeting inflammation in chronic wounds with MCC950 did not improve healing in mice. This NLRP3 inflammasome inhibitor even impaired wound closure in obese models, suggesting it may hinder chronic wound healing.
Area of Science:
- Wound healing research
- Inflammation and immunology
- Drug discovery and development
Background:
- Chronic wound incidence is rising, particularly in aging populations.
- Inflammation, including macrophage activity, is crucial for wound healing.
- The NLRP3 inflammasome is a key target for inflammatory diseases.
Purpose of the Study:
- To investigate the efficacy of MCC950, a selective NLRP3 inflammasome inhibitor, in murine models of acute and chronic wounds.
- To assess MCC950's impact on topical inflammation and wound healing.
- To evaluate MCC950's effect on re-epithelialisation and angiogenesis.
Main Methods:
- Utilized MCC950, a small molecule inhibitor of NLRP3 inflammasome.
- Administered MCC950 topically and orally in wild-type C57Bl/6 mice.
- Tested MCC950 in obese murine models to assess effects on wound healing.
Main Results:
- MCC950 treatment showed no significant difference in wound healing when applied topically or orally in wild-type mice.
- MCC950 impaired wound healing in obese mice.
- The inhibitor did not improve re-epithelialisation or angiogenesis and did not alter macrophage polarisation.
Conclusions:
- MCC950 may inhibit chronic wound closure.
- Targeting NLRP3 inflammasome with MCC950 is not a beneficial strategy for improving chronic wound healing.
- Further research is needed to understand MCC950's role in wound-associated macrophage polarisation.
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