Wound Healing Kinetics of the Genetically Diabetic Mouse
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Wound tissues for histological assessment were collected in the period when 50% closure was reached (8–13 days post operation).26
The level of contraction of a wound can be measured by the dermal gap. The dermal gap of 1.0 cm2 reduced in size of 8.3 mm ± 1 mm on day 9. Microscopic quantification of the epithelial gap (the open portion of the wound) on the same day resulted in 5.8 mm ± 2 mm (Figure 2A, 2B).30,31
Microscopic analysis of wounds mid-healing demonstrated less inflammatory infiltrates in diabetic wounds than wild-type wounds.26 The granulation tissue formed by the db/db mouse in the middle of the lesion of a 1.0 cm2 full-thickness wound was 78% less when compared to wild type animals. Similar results were seen when granulation tissue thickness was measured—79% reduction (Figure 2A, 2C).26,30,31 The number of blood vessels on the same day was 5.7 ± 5.8 per high power field at
Blood vessel density in the granulation tissue reached 4 ± 3% and cell proliferation was found up to 20 ± 7% on day 9, as assessed by immunohistochemistry.
Diabetic mice and hyperglycemia. Db/db mice showed a diabetic-hyperglycemic phenotype with significantly greater blood sugar levels (590 mg/dL ± 6 mg/dL) compared to their corresponding wild-type counterparts (285 mg/dL ± 7 mg/dL).26
Genotype analysis. Genotype analysis revealed a band at 135 bp in wild type mice (Figure 6A). Mice heterozygous (db/+) for the point mutation, showed a 135 bp and 108 bp bands (Figure 6B). Mice homozygous for leptin receptor mutation (db/db) showed only the 108 bp band (Figure 6C).
Considering the increased prevalence of diabetes type 2 in the general population, the development of a reliable animal model, and the standardization of measurement techniques and study designs, are crucial aspects to facilitate improvements in therapies that seek to provide an efficient clinical translation. Among all animal models used, the db/db mouse model is the one that is most commonly used in wound care.
Different mechanisms contribute to wound closure kinetics, such as wound contraction and re-epithelialization. In the db/db mouse, the possibility to capture the different wound closure mechanisms makes it possible to quantify early effects of treatments, whereas vigorous wound contraction in wild type mice easily plaster effects. In the authors’ experience with the db/db mouse it is crucial to study the relative contribution to healing from re-epithelialization and contraction in order to better understand the effects of a therapy. For example, while for some wounds, such as a chronic foot ulcer, the most important goal is to achieve faster wound closure regardless from its mechanism, others would benefit mainly from inhibition of contraction (eg, joint wounds, wounds in cosmetic relevant positions, or burn wounds covering a larger surface).
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