Quantitative and reproducible murine model of excisional wound healing

Abstract

The goal of animal wound healing models is to replicate human physiology and predict therapeutic outcomes. There is currently no model of wound healing in rodents that closely parallels human wound healing. Rodents are attractive candidates for wound healing studies because of their availability, low cost, and ease of handling. However, rodent models have been criticized because the major mechanism of wound closure is contraction, whereas in humans reepithelialization and granulation tissue formation are the major mechanisms involved. This article describes a novel model of wound healing in mice utilizing wound splinting that is accurate, reproducible, minimizes wound contraction, and allows wound healing to occur through the processes of granulation and reepithelialization. Our results show that splinted wounds have an increased amount of granulation tissue deposition as compared to controls, but the rate of reepithelialization is not affected. Thus, this model eliminates wound contraction and allows rodents' wounds to heal by epithelialization and granulation tissue formation. Given these analogies to human wound healing, we believe that this technique is a useful model for the study of wound healing mechanisms and for the evaluation of new therapeutic modalities.

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

“…A donut-shaped silicone splint was adhered around the wound to minimize wound contraction; the splinting did not influence re-epithelialization. 30 This model closely parallels human wound healing. The adherent macrophages were incubated with 100 nmol/L 14S,21R-diHDHA in a dish (37°C, 5% CO 2 , 24 hours), resuspended in RPMI 1640 medium, and used as 14S,21R-diHDHA-treated macrophages.…”

“…16,30,31 Briefly, paired 5-mm circular, full-thickness wounds were made symmetrically along the midline on the dorsal skin of mice. Two days later, 14S,21R-diHDHA (50 ng/wound) or macrophages and 14S,21R-diHDHAtreated macrophages (10 6 cells/wound) were applied to the wound bed (10 L/bed) and were injected intradermally at four points (10 L/site) distributed evenly near the wound edge (50 L total/wound).…”

“…Cryosections (10 m thick) of wounds from db/db mice (day 8 after wounding) and 12/15-LOX Ϫ/Ϫ or C57BL/6J mice (day 5 after wounding) were analyzed to determine the epithelial gap and granulation tissue formation after H&E staining. The splint has a constant area, and it was used to normalize the wound sizes 30 ; therefore, the original epithelial gap (original wound size) was equal in each wound (5 mm in diameter).…”

“…30,33 The relative epithelial gap was calculated as a percentage: (advancing epithelial gap/original epithelial gap) ϫ 100. Granulation tissue locates between epidermal layer and subcutaneous layer, and exhibits tight granular morphology.…”

An Improved Humanized Mouse Model for Excisional Wound Healing Using Double Transgenic Mice

“…For these reasons, mice are one of the most commonly used laboratory animals for research. [3][4][5] The use of mice for wound healing has been problematic in the past, due to the presence of a subcutaneous layer of striated muscle, the panniculus carnosus, found in mice but not humans. The only analogous muscle in humans is the platysma muscle in the neck.…”