Skin layer mechanics

The human skin is composed of several layers, each with an unique structure and function. Knowledge about the mechanical behavior of these skin layers is important for clinical and cosmetic research, such as the development of personal care products and the understanding of skin diseases. Until today, most research was performed in vivo and focused on the mid-layer, the dermis. However, clinical and cosmetic applications require more detailed knowledge about the skin layers at the skin surface, the viable epidermis and stratum corneum, and the deeper lying hypodermis. Studying these layers in an in vivo set up is very challenging. The different length scales, ranging from µm for the stratum corneum to cm for the hypodermis, the interwoven layered structure and the inverse relation between penetration depth and resolution of non-invasive measurement techniques form major problems. As a consequence, hardly any data are available for the viable epidermis and hypodermis and reported data for stratum corneum are inconsistent. The aim of this thesis was therefore to characterize the mechanical behavior of individual skin layers in vitro and, for that, to develop the required experimental procedures. It was considered essential to perform experiments with samples of consistent quality in an accurate measurement set-up in a well-controlled environment. Various isolation and preservation methods were investigated on tissue performance, reproducibility and ease of handling. Because of the inhomogeneous layered structure of the upper skin layers, mechanical properties of the stratum corneum and viable epidermis were determined for various loading directions. First, the stratum corneum and epidermis were subjected to shear over a wide frequency range and with varying temperature and humidity. The typical geometry of the upper skin layers required preliminary testing series in order to define the right experimental conditions to ensure reliable results. Subsequently, micro-indentation experiments were applied using a spherical tip with a relatively large diameter. The Young¿s moduli were derived via an analytical and numerical method. Because of the complexity of measuring those skin layers, it was decided to focus on small deformations first. For both types of loading, result were highly reproducible. The shear tests demonstrated that the shear modulus is influenced by humidity but not by temperature in the measured range. If the skin is compressed with an indenter, the stiffness of the epidermis and stratum corneum, which is about 1-2 MPa, is about a factor 100 higher than for shear. No significant differences in stiffness between the stratum corneum and viable epidermis were observed per loading type. The results of these tests prove that it is essential to take into account the highly anisotropy of the tissue in numerical models. Rheological methods were developed to study the mechanical response of the subcutaneous adipose tissue. In the small linear viscoelastic strain regime, the shear modulus showed a frequency- and temperature-dependent behavior and is about 7.5 kPa at 10 rad/s and 37°C. Time-Temperature Superposition is applicable through shifting the shear modulus horizontally. A power-law function model was able to describe the frequency dependent behavior at constant temperature as well as the measured stress relaxation behavior. Prolonged loading at small strains results into a dramatic stiffening of the material. Loading-unloading cycles showed that this behavior is reversible. In addition, various large strain history sequences showed that stress-strain responses are reproducible up to 0.15 strain. When the strain further increases, the stress is decreasing for subsequent loading cycles and, above 0.3 strain, the stress response becomes stationary. These results showing time and strain effects indicate that adipose tissue likely behaves as an (anti-)thixotropic material, meaning that a constitutive model should contain parameters to describe the build-up and breakdown of the material structure. However, further experimental research is needed to fully understand the thixotropic behavior before such a model can be worked out in detail. In conclusion, this thesis evaluates the mechanical behavior of stratum corneum, epidermis and hypodermis using various in vitro set-ups. It was proven that for all skin layers reproducible results can be obtained. The research was aimed at developing reliable methods to determine the mechanical behavior of individual human skin layers. Future work should be focused on the relationship between mechanical properties and tissue deformation using imaging techniques and heading to the determination of the skin¿s failure behavior in relation to clinical and cosmetic treatments

Modeling Small Strain Behavior of the Subcutaneous Fat Layer

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Mechanical properties of the epidermis and stratum corneum determined by submicron indentation in vitro

The outer skin layers are important drug and vaccine delivery targets in the treatment of diseases. These skin layers possess some important characteristics making them favorable sites for pain-free delivery with minimal damage: a rich population of immunologically sensitive cells as well as the lack of blood vessels and sensory nerve endings [1]. Until today, however, the development of effective cell targeting methods is acquainted with many challenges. A collective shortcoming is a poor understanding of the key mechanical properties of the outer skin layers, e.g. the stratum corneum and epidermis. The anisotropic, dynamic and very complex nature of skin makes it difficult to perform proper mechanical testing as well as to obtain reliable, reproducible data. The stratum corneum is an effective physical barrier of dead cells with a “brick-and-mortar” structure, while the viable epidermis mainly consists of actively migrating keratinocytes constantly undergoing massive morphological and compositional changes. As a consequence, the structure differences among the skin layers lead to significant variations in mechanical properties. Since there is no method available to determine the mechanical behavior of isolated viable epidermis in vivo or in vitro, the mechanical behavior of epidermis and stratum corneum only are investigated here. A commercially available indentation system has been adapted to enable the measurement of these thin soft tissues in an in vitro set up. Combining the outcomes of the two skin layer types leads to an assessment of the contribution of the viable epidermis to the mechanical behavior of skin. To our knowledge, no data have been published yet regarding mechanical bulk properties of (viable) epidermis, while no consistency exists with respect to those of the stratum corneum