Multiscale mechanics of skin
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Date
2024
Publication Type
Doctoral Thesis
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yes
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Abstract
As one of the largest organs in the human body, the skin constitutes our primary structural and chemical barrier against influence from the surroundings. In our daily lives, the skin plays an important role in the hydration and temperature regulation of our bodies, in addition to protecting the deeper tissues of the body from harmful UV-radiation.
From a mechanical perspective, skin is a fascinating material, exhibiting strongly nonlinear strain-stiffening behavior in addition to a remarkable tear resistance. The multi-faceted role of the skin can be attributed to its complex microstructure. Broadly speaking, skin can be divided into three main layers; the epidermis, the dermis and the hypodermis. The epidermis, the outermost layer of the skin, constitutes the primary barrier function through a tightly packed arrangement of keratinocyte cells. The main load-bearing capacities of the skin are typically attributed to the dermis, in which the reticular structure is composed of a complex network of collagen and elastin fibers, maintained by the residing fibroblast cells. Ultimately, the hypodermis is mainly composed of fat tissue, and serves the role of protecting the underlying tissue against impact as well as important functions for energy storage and temperature regulation.
In this thesis, experiments at different length-scales are combined with computational modeling to enhance the understanding of the mechanical behavior of skin.
It is now well-established that the homeostasis of skin functions in a fine interplay between mechanical and chemical cues. Furthermore, the mechanobiology of skin has been documented to be highly relevant for a wide range of conditions such as skin fibrosis, the healing of skin wounds and skin growth.
In the first part of the thesis, the biomechanical properties of skin are assessed on the tissue length-scale using noninvasive biomechanical skin characterization devices. Although a variety of different functional principles are used in the assessment of skin, few quantitative comparisons between different principles have been done. Herein, three commonly used functional principles, suction, dynamic shear load and indentation, are analyzed. Preliminary measurements on synthetic materials allowed to rationalize the different principles, indicating a similar capability of detecting changes in the underlying substrate stiffness between the devices. Measurements on healthy human volunteers reveals a similar tendency to detect differences in apparent stiffness between different body locations, albeit with large differences in the reliability between the different principles, which is devoted to the influence from boundary conditions. Ultimately, an inverse finite element model is used to rationalize the results, with important implications for the interpretation of the measurement results.
In the second part, the mechanical properties of skin are investigated on the local length-scale. First, murine excisional wounds are assessed with atomic force microscopy based indentation tests to resolve previously reported conflicting findings on the mechanical behavior of healing skin wounds. When comparing the apparent stiffness of different regions in the wound, large differences are documented. In line with previous findings, the apparent stiffness of the newly forming tissue is documented to be significantly lower than the healthy tissue. In particular, the present work identifies the hyperproliferative epithelium, a cellular layer forming during the initial phases of wound healing, as a potential provider of structural integrity to the wound. Measurements on wounds from later time points identify the healing progression of the tissue. To assess the influence from local topography on the apparent stiffness in the different material regions, topographic information obtained from atomic force microscopy imaging is implemented in a bi-phasic material model.
Next, the influence of intrinsic ageing on the biomechanical properties of skin are assessed in murine tissue. Considering baby, adult and very old mice with atomic force microscopy based indentation tests, significant differences between the baby and adult animals are documented. Comparison with uniaxial tension experiments at the tissue length-scale reveal that very young and very old skin respond differently to hyper-physiological loading.
Ultimately, the development and proof-of-concept of an in vivo stretching device is presented. Motivated by typical discrepanices of several orders of magnitude when comparing experimental results from different length-scales, a protocol to preserve tissue stretch during the preparation of tissue for local indentation tests is presented. When comparing the apparent modulus from stretched and unstretched samples, a significant increase is documented.
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published
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Examiner : Mazza, Edoardo
Examiner : Avril, Stéphane
Examiner : Hopf, Raoul
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ETH Zurich
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Subject
Skin mechanics; Mechanobiology; AFM; Wound healing
Organisational unit
03605 - Mazza, Edoardo / Mazza, Edoardo
Notes
Funding
179012 - Skin biomechanics and mechanobiology for wound healing and tissue engineering (SNF)