Degradation of biomechanical properties and impaired wound healing in the back skin of mice with type 1 diabetes mellitus: a quantitative study

To investigate the mechanisms underlying the reduced biomechanical properties and impaired wound healing in the dorsal skin of streptozocin (STZ)-induced type 1 diabetes mellitus (T1DM) mice.

Forty male C57BL/6 mice (8 weeks old, weighing 20~25 g) were randomly divided into wild-type (WT, n=20) and T1DM (n=20) groups. After the mice were inflicted with full-thickness skin resection (circular, 1 cm in diameter, in both sides of the back midline), atomic force microscopy (AFM) and scanning electron microscopy (SEM) were employed to assess the Young's modulus, relaxation rate, and collagen arrangement of the skin, and HE, Masson's trichrome, Sirius red, Gordon-Sweet, and Victoria blue staining were all applied to evaluate the epidermis and granulation tissue, total collagen content, ratio of type Ⅲ to type Ⅰ collagen, reticular fiber content, and elastic fiber content. Immunohistochemical assay and Western blotting were conducted to quantify the expression of type Ⅰ and type Ⅲ collagen proteins. Flow cytometry and immunofluorescence staining of paraffin sections were performed to detect the transformation of myofibroblast in wound tissues.

On day 21 post-wounding, the dorsal skin of T1DM mice exhibited significantly reduced stiffness, strength, and resilience compared to the conditions in the WT group (P<0.05). During and after healing, T1DM mice showed decreased collagen and elastic fibers, an increased ratio of type Ⅲ to type Ⅰ collagen, and increased reticular fibers, all with statistical significance (P<0.05). Additionally, there was a significant reduction in myofibroblast transformation during the early stages of wound healing in the T1DM group (P<0.05).

T1DM inhibits the transformation of fibroblasts into myofibroblasts, leading to impaired wound healing and reduced biomechanical properties in the dorsal skin of mice.