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Updated: Aug 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
Full-thickness wounding of the mouse tail as a model for delayed wound healing: accelerated wound closure in Smad3
Vincent Falanga1, David Schrayer, Jisun Cha
1Department of Dermatology, Roger Williams Medical Center, Elmhurst Building, 50 Maude Street, Providence, RI 02908, USA. vfalanga@bu.edu
Abstract:
Experimentally induced wounds in animal models are useful in gaining a better understanding of the cellular and molecular processes of wound healing, and in the initial evaluation of the safety and effectiveness of potential therapeutic agents. However, studying delayed healing has proved difficult in animals, whose wounds heal within a few days. In this report, we describe a novel method for establishing mouse wounds that require up to 3 weeks or more for complete closure, and we show the validity of this model in Smad3 null mice, which are known to display accelerated healing. Full-thickness wounds, measuring 0.3 by 1.0 cm, were made down to fascia on the dorsal aspect of the mouse tail in Smad3 knock-out mice and control littermates, approximately 1 cm distal to the body of the animal. The wounds were left to heal by secondary intention and were assessed histologically by computerized planimetry for wound closure at various times after wounding. The wounds in wild-type mice displayed delayed healing, with full closure occurring between 14 and 25 days after wounding. Complete closure of similar wounds in Smad3 null mice healed 30 percent faster (p < 0.01). By immunostaining for ki67, a marker for proliferation, Smad3 null animals also showed increased proliferation of dermal wound cells by day 4 after wounding. Cultured dermal fibroblasts from Smad3 null mice had increased baseline DNA synthesis and, interestingly, an enhanced response to transforming growth factor-beta1. By Western blot analysis, Smad3 null mice fibroblasts showed a compensatory increase in mitogen-activated protein kinase phosphorylation in response to transforming growth factor-beta1, suggesting that mitogen-activated protein kinase overcompensation together with loss of Smad3 may be involved in the modulation of faster healing. We conclude that this novel tail-wounding model may be useful for studying delayed wound closure.
Insights
Researchers developed a novel mouse tail wound model for studying delayed healing. Smad3 null mice showed accelerated wound closure, indicating this model
Area of Science:
- Wound healing research
- Animal models in biomedical research
- Dermatology and regenerative medicine
Background:
- Animal models are crucial for understanding wound healing and testing therapies.
- Existing models have limitations in studying delayed wound healing due to rapid natural healing processes in animals.
- Smad3 null mice are known to exhibit faster wound healing, making them a relevant model for comparative studies.
Purpose of the Study:
- To establish and validate a novel mouse tail-wounding model for studying delayed wound healing.
- To investigate the healing characteristics of this model in Smad3 null mice compared to wild-type controls.
- To explore the cellular and molecular mechanisms underlying accelerated healing in Smad3 null mice within this model.
Main Methods:
- Creation of full-thickness dorsal tail wounds (0.3x1.0 cm) in Smad3 knock-out and wild-type littermate mice.
- Wound assessment via histological analysis and computerized planimetry for closure time.
- Immunostaining for Ki67 (proliferation marker), fibroblast DNA synthesis assays, and Western blot analysis for signaling pathway activation (MAPK).
Main Results:
- Wounds in wild-type mice exhibited delayed healing, closing between 14-25 days.
- Smad3 null mice demonstrated significantly faster wound closure, approximately 30% quicker (p < 0.01).
- Smad3 null mice showed increased Ki67+ cells, enhanced fibroblast DNA synthesis, and elevated MAPK phosphorylation in response to TGF-β1.
Conclusions:
- The developed mouse tail-wounding model effectively simulates delayed wound healing.
- Smad3 deficiency accelerates wound healing, potentially through enhanced proliferation and altered TGF-β1 signaling via MAPK pathways.
- This model provides a valuable tool for investigating delayed wound healing and potential therapeutic interventions.
