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Multiscale modeling of the skin’s biomechanics and aging
Dissertation   Open access

Multiscale modeling of the skin’s biomechanics and aging

Nathaniel James Witt
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2024
DOI: 10.25820/etd.007438
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Abstract

Skin is a complex multilayered tissue that regulates temperature and hydration, provides sensory information to the nervous system, and protects against chemical, biological, and physical assaults from the environment. It also must be distensible to accommodate body movement and tough enough to withstand physical forces that could lead to tissue damage. It is increasingly clear that the local mechanical environment within a tissue provides important cues that regulate normal tissue function. These cues are highly dependent on the local composition and organization of the extracellular matrix, as well as mechanical forces transmitted across spatial scales of the tissue. The effects of disease, aging, injury, and repair of the skin all depend heavily on how macroscopic tissue-level forces distribute down to the microscale level of cells and matrix proteins. Thus, to understand dynamic changes in skin function, including those associated with aging and injury, it is critical that one takes a multiscale perspective. However, investigating the multiscale structure-function relationships of skin faces challenges due to experimental limitations and the difficulty in replicating microstructural kinematics using standard computational modeling techniques. To better understand the skin’s biomechanics, we constructed image based multiscale mechanical models (MSM) of mouse skin and represented the collagenous dermis with experimental images of dermal microstructure acquired during mechanical testing. Three models that spanned the cases of highly aligned, moderately aligned, and nearly random fiber networks were examined and compared to the data acquired from uniaxially stretched skin. We also investigated alterations in the skin with aging by simulating increased nonenzymatic crosslinking with discrete fiber networks, representing changes in collagen fiber properties and fiber-fiber connectivity (i.e., network fragmentation). Furthermore, we analyzed the influence of increased collagen fragmentation on the mechanical behavior and failure properties of skin using notched multiscale models loaded in tension. These findings contribute to a better understanding of the dermal microstructure with changes in alignment and age dependent alterations with nonenzymatic crosslinking.
Aging Biomechanics Collagen Dermis Fiber networks Multiphoton microscopy

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