Lessons Learned from Murine Models of Wound Healing
Wound repair involves a number of highly complex biological processes that can be studied in a comprehensive manner through in vivo studies. Various murine models of wound healing have been effectively utilized to address several wound types. Hundreds of mouse models provide more validated reagents than other animals, and over 1,000 generated mutant loci, often sharing the same gene mutation as the patient or condition under investigation. Mice are also smaller than other experimental animals, making them both economically and logistically ideal for elaborate research work.
The excisional wound healing model is one that is most commonly used, and employs a technique to mitigate healing characteristics specific to the mouse dorsum or panniculosus carnosus layer. Silicone rings are used as splints to hold the wound margins in place. This prevents margin contracture which, in turn, increases the amount and duration of re-epithelialization and granulation tissue formation characteristic of human wound healing. Thus, the excisional wound healing model is excellent for studying human deficits in cellular activity, matrix assembly, and other phenomena.
Human repair mechanisms are recapitulated and carefully studied by other models of wound healing as well. For example, mouse models of cutaneous ischemia and reperfusion injury provide insight into impaired neovascularization conditions found in aged and diabetic patients. Injuries caused by a lack of circulation (ischemia) followed by restoration of circulatory function (reperfusion) are also highly implicated in pressure ulcers. In the ischemic skin flap model, a three-sided flap is cut from the dorsum of the mouse, and a silicone barrier underneath the exposed skin isolates the upper layer, providing a reproducible ischemic gradient from which mechanisms of blood vessel formation are investigated.
As another example, mouse models of skin fibrosis provide important insight into fibroproliferative diseases that are chemically or radiation induced. Skin fibrosis is also induced in transgenic mice or by xenograft activation. Furthermore, exogenous mechanical loads are applied to incisions to induce hypertropic scar formation. Additional murine models closely model other human wound healing conditions as well, providing unique avenues of insight that cannot easily be obtained by other means.
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