Mechanical and Biological Evaluation of Murine Dermis in the Scope of Pressure Ulcer Formation William Meador, Claire Long, Hannah Story, Manuel Rausch.

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Mechanical and Biological Evaluation of Murine Dermis in the Scope of Pressure Ulcer Formation William Meador, Claire Long, Hannah Story, Manuel Rausch   The University of Texas at Austin, Department of Biomedical Engineering, Department of Aerospace Engineering and Engineering Mechanics 2501 Speedway, Austin, Texas, 78712, USA E-mail: william.meador@utexas.edu Abstract Pressure ulcers are a significant cause of morbidity and warrant clinical treatment of over 2.5 million Americans annually [1]. Similar to human skin, murine skin’s mechanical response strongly determines its susceptibility to pathological insults such as pressure ulcers. Yet, a detailed characterization of murine skin mechanics and microstructural composition is lacking, impairing our ability to use murine models to understand the role of mechanics in pathologies such as pressure ulcers in the elderly. Introduction Murine skin is one of the most frequently used animal models in dermatological sciences [2]. Murine skin’s mechanical response to biaxial and compressional loading strongly determines its susceptibility to pathological insults. This response is governed by its complex microstructural composition and multiphasic nature.  Furthermore, mechanical properties vary regionally and are age-dependent. Therefore, it is imperative to understand the mechanical behavior of skin and how it relates to the skin microanatomy. Moreover, to understand a disease state, one must first understand the healthy precursor. Therefore, we set out to perform age-dependent and regionally varying mechanical analyses of healthy murine skin. We excised mouse skin tissue from healthy 12 week and 52 week male C57BL/6 mice at both dorsal and ventral anatomical regions. To characterize the mechanics of each tissue group, we evaluated the skin in: Planar biaxial tension (Fig. 1) Uniaxial confined compression (Fig. 2) In vivo pre-strain (Fig. 3) Moving forward we will employ biological evaluations to inform the relative contributions of elastin, collagen, and ground substance to the constitutive behavior of our samples. 2. Results We successfully completed the collection of biaxial, pre-strain and compression data. Analysis has been completed for biaxial and pre-strain data. Biaxial data reveal that all skin samples, independent of location and age, showed a classic nonlinear response to biaxial stretch. We captured the sample’s mechanical response from the biaxial data via a Fung-type constitutive law model fit. Murine skin’s biaxial response is also dependent on location, direction, and age (Fig. 4A-B). Additionally, pre-strain data reveal that mouse skin is significantly pre-strained and it varies with location, direction, and age (Fig. 5). Stress-relaxation compression data has been collected for finite element simulation that will derive the time-varying mechanical response of murine skin to compression (Fig 6 for typical data). Moving forward we will employ the following biological evaluations to inform the relative contributions of elastin, collagen, and ground substance to the constitutive behavior: 2-Photon microscopy – fiber orientation map Histology Dehydration – biphasic volume fractions In conclusion, these data, together with the remainder of our analyses, will provide a comprehensive mechanical and biological model of murine skin. 3. Discussion This data, in the scope of pressure ulcer formation, may explain why certain age populations and anatomical regions are more susceptible to pressure ulcer formation. It is my expectation that once published, this data will be used as the control data for a future study comparing the mechanics and physiology of healthy versus ulcerated tissue in murine models. A B Fig. 4 Cauchy stress vs. stretch for biaxial response summary Fig. 1 Planar biaxial tension Fig. 2 Confined compression rig Fig. 6 Typical compression data ________________________ References [1] Sen et al. Wound Repair Regen, 2009 [2] Chen et al. J Dermatol Sci, 2008 Fig. 3 In vivo pre-strain configuration with ink stamp Fig. 5 Pre-strain data summary Proceedings of the 2018 ASEE Gulf-Southwest Section Annual Conference The University of Texas at Austin April 4-6, 2018