Abstract: 【Abstract】 Objective To investigate the inhibitory effect and mechanisms of action of mucopolysaccharide polysulfate cream on hypertrophic scar formation. Methods Circular full-thickness wounds with a diameter of 6 mm were established in both ears of 16 New Zealand white rabbits to establish a rabbit ear model of hypertrophic scar. There were 3 scar wounds in each rabbit ear. About 14 days after the operation, scar wounds on the left ear were topically treated with mucopolysaccharide polysulfate cream, and served as the experimental group; scar wounds on the right ear were topically treated with the cream vehicle, and served as vehicle control group. The dosage of topical agents for one rabbit ear was approximately 0.4 g, which were given twice a day for 6 consecutive weeks. Scar tissues were collected and subjected to hematoxylin and eosin （HE） staining, Masson staining and immunohistochemical study on days 0, 14 and 42, that is, 14, 28 and 56 after operation respectively, so as to evaluate histopathological scores, measure the scar thickness and collagen fiber density, and determine the expression of type Ⅰ and Ⅲ collagen and the ratio of type Ⅰ/Ⅲ collagen. The t test and one-way analysis of variance were used to compare the indices between groups. Results Compared with pretreatment histopathological manifestations, HE staining showed extensive extracellular matrix deposition, inflammatory cell infiltration and local hyperemia in the control group after 42-day treatment, but no obvious changes in the experimental group. The pathological scores of scar tissues on the rabbit ears significantly increased over time in the control group （days 0, 14 and 42: 4.16 ± 1.61, 6.50 ± 1.46, 6.53 ± 1.34, respectively; F = 13.69, P = 0.001）, while there was no significant change in the experimental group （days 0, 14 and 42: 4.65 ± 1.52, 5.13 ± 1.83, 5.38 ± 1.60, respectively; F = 0.78, P > 0.05）. Masson staining showed extremely high content of collagen fibers dyed dark blue in the control group on day 42, but there was a decrease in the content of collagen fibers in the experimental group; with the increase in treatment duration, the thickness of scar tissues significantly increased in the control group compared with that before treatment （F = 5.64, P = 0.007）, while there was no significant change in the experimental group （F = 1.48, P > 0.05）. Immunohistochemical study revealed no significant change in the expression of type Ⅲ collagen in either the experimental group or the control group at any of the above time points compared with that on day 0 （F = 0.22, 0.92, respectively, both P > 0.05）, but the expression of type Ⅰ collagen and the ratio of type Ⅰ/Ⅲ collagen significantly increased in the control group （F = 7.47, P < 0.001; F = 4.70, P = 0.005, respectively）. On day 42, the expression of type Ⅰ collagen and the ratio of type Ⅰ/Ⅲ collagen significantly decreased in the experimental group compared with the control group （t = 3.04, P = 0.007; t = 2.35, P = 0.030, respectively）. Conclusion Topical mucopolysaccharide polysulfate cream is effective in preventing and inhibiting scar hypertrophy by reducing the scar thickness and inhibiting the collagen fiber hyperplasia and type I collagen expression.

Key words: Cicatrix, Models, animal, Lycosaminoglycans, Fibrillar collagens, Collagen, Mucopolysaccharide polysulfate, Hyperplasia