The multiscale characterization and constitutive modeling of healthy and type 2 diabetes mellitus Sprague Dawley rat skin

Abstract

In type 2 diabetes mellitus (T2DM), elevated glucose level impairs the biochemistry of the skin which may result in alteration of its mechanical and structural properties. The several aspects of structural and mechanical changes in skin due to T2DM remain poorly understood. To fill these research gaps, we developed a non-obese T2DM rat (Sprague Dawley (SD)) model for investigating the effect of T2DM on the in vivo strain stress state, mechanical and structural properties of skin. In vivo strain and mechanical anisotropy of healthy and T2DM skin were measured using the digital imaging correlation (DIC) technique and DIC coupled bulge experiment, respectively. Fluorescence microscopy and histology were used to assess the collagen and elastin fibers microstructure whereas nanoscale structure was captured through atomic force microscopy (AFM). Based on the microstructural observations, skin was modeled as a multilayer membrane where in and out of plane distribution of collagen fibers and planar distribution of elastin fibers were cast in constitutive model. Further, the state of in vivo stresses of healthy and T2DM were measured using model parameters and in vivo strain in the constitutive model. The results showed that T2DM causes significant loss in in vivo stresses (p < 0.01) and increase in anisotropy (p < 0.001) of skin. These changes were found in good correlation with T2DM associated alteration in skin microstructure. Statistical analysis emphasized that increase in blood glucose concentration (HbA1c) was the main cause of impaired biomechanical properties of skin. The presented data in this study can help to understand the skin pathology and to simulate the skin related clinical procedures. STATEMENT OF SIGNIFICANCE: Our study is significant as it presents findings related to the effect of T2DM on the physiologic stress strain, structural and mechanical response of SD rat skin. In this study, we developed a non-obese T2DM SD rat model which mimics the phenotype of Asian type 2 diabetics (non-obese). Several structural and mechanical characterization techniques were explored for multiscale characterization of healthy and T2DM skin. Further, based on microstructural information, we presented the constitutive models that incorporate the real microstructure of skin. The presented results can be helpful to simulate the realistic mechanical response of skin during various clinical trials.

Keywords: Anisotropy; Constitutive modeling; Multiscale characterization; Physiologic stresses; Skin; T2DM.