Dose-dependent effects of mitomycin С in non-healing wound modeling

Non-healing or chronic wounds are widely distributed complications of several pathologic states. A study of healing mechanisms requires an adequate animal model of such wounds. Use of rodents, one of the most available laboratory animals, is linked with some problems: wound edge contraction that precedes re-epithelialization. Mitomycin C (MMC), as a pharmacological inhibitor of cell proliferation, can be used in chronic wound modelling. The aim. The objective of the research was to create a model of non-healing (chronic) wound by surgically limiting its contraction and inhibiting recovery rate with the pharmaceutical agent mitomycin C (MMC). Materials and methods. Male Balb/c mice were used. Two layers of skin were pierced through, resulting in the simultaneous formation of two wounds (~0.6 cm3), whose edges were sutured surgically to hinder their contraction. Wounds were additionally treated with 0.5, 1, 2, and 3 mg/ml MMC. The delay of healing was assessed by measuring wound area and by morphological and histological examination. Results. The application of 2 and 3 mg/ml MMC for surgically fortified excision wounds resulted in a significantly increased area by day 21 and 28 compared with groups treated with lower doses. Also, wounds had loci of necrosis and infiltration. Delayed re-epithelialization and irregular collagen fibres were observed histologically after treatment with 2 and 3 mg/ml. Considering the absence of differences between wounds treated with 2 and 3 mg/ml MMC and its potential toxic effects, 2 mg/ml was recommended for non-healing wound modelling. Conclusions. An optimal model of non-healing (chronic) wound was created. The main aspects of the murine model can be outlined as follows: the use of surgical fixation of wound edges to a dense polymer base and treatment with 2 mg/ml MMC