Marion Geerligs

Linear viscoelastic behavior of subcutaneous adipose tissue

Subcutaneous adipose tissue contributes to the overall mechanical behavior of the skin. Until today, however, no thorough constitutive model is available for this layer of tissue. As a start to the development of such a model, the objective of this study was to measure and describe the linear viscoelastic behavior of subcutaneous adipose tissue. Although large strains occur in vivo, this work only focuses on the linear behavior to show the applicability of the described methods to adipose tissue. Shear experiments are performed on porcine samples on a rotational rheometer using parallel plate geometry. In the linear viscoelastic regime, up to 0.1% strain, the storage and loss modulus showed a frequency- and temperature-dependent behavior. The ratio between the two moduli, the phase angle, did not show any dependency on temperature and frequency. The shear modulus was found to be 7.5 kPa at 10 rad/s and 37 degrees C. Time-temperature superposition was applicable through shifting the shear modulus horizontally. A power-law function model was introduced to describe both the frequency dependent behavior at constant temperature and the stress relaxation behavior. In addition, the effect of snap freezing as a preservation method was analyzed. Histological examination demonstrated possible tissue damage after freezing, but the mechanical properties did not change. Since results were reproducible, it is concluded that the methods we used are most probably suited to explore the non-linear behavior of subcutaneous adipose tissue.

Linear shear response of the upper skin layers

This study presents an in vitro experimental method to determine shear properties of the epidermis. Shear tests were performed with a parallel plate rheometer on samples of stratum corneum and the viable epidermis. The method was validated on very thin silicon sheets. Preliminary test were performed to determine the linear viscoelastic range, the effect of normal loading on the sample and the time to reach equilibrium after changes of temperature and relative humidity. The study shows that reproducible results can be obtained for the shear properties of epidermis in an in vitro set up. The dynamic shear modulus for stratum corneum ranges from about 4-12 kPa, decreasing with increasing relative humidity. The values are considerably lower than the shear modulus value based on tensile Youngs moduli in the literature, indicating a considerable anisotropic material behavior. Results for the epidermis were of the same order of magnitude, but were less consistent possibly due to a less well-defined tissue composition.

Does subcutaneous adipose tissue behave as an (anti-)thixotropic material?

Although subcutaneous adipose tissue undergoes large deformations on a daily basis, there is no adequate mechanical model to describe the transfer of mechanical load from the skin throughout the tissue to deeper layers. In order to develop such a non-linear model, a set of experimental data is required. Accordingly, this study examines the long term behavior of adipose tissue under small strain and its response to various large strain profiles. The results show that the shear modulus dramatically increases to about an order of magnitude after a loading period between 250 and 1250 s, but returns to its initial value within 3 h of recovery from loading. In addition, it was observed that the stress-strain responses for various large strain history sequences are reproducible up to a strain of 0.15. For increasing strains, the stress decreases for subsequent loading cycles and, above 0.3 strain, tissue structure changes such that the stress becomes independent of the applied strain. From the results, it can be concluded that adipose tissue likely behaves as an (anti-) thixotropic material and that a Mooney-Rivlin model might be appropriate to simulate behavior at physiologically relevant high strains. However, before the model is developed more fully, further experimental research is needed to ratify that the material is (anti-)thixotropic.

Modeling Small Strain Behavior of the Subcutaneous Fat Layer

Until today mechanical properties of the subcutaneous fat layer have hardly been considered as important and, hence, a constitutive model describing its behavior is lacking. However, numerical models including the subcutaneous fat layer are needed in a wide field of applications such as skin device contact, needle insertion procedures, and the removal of skin adhesives. The aim of this study is to develop a thorough constitutive model describing the mechanical behaviour of subcutaneous adipose tissue, which can be implemented in numerical models. The constitutive model formulation is based on rheological experiments in vitro. Here, the first results are presented.

Linear Viscoelastic Behavior of Adipose Tissue

Adipose tissue plays an important role in the load transfer between different tissue structures like skin and muscle. Though a plethora of papers can be found on properties of these surrounding tissue layers, only few papers addressed the properties of the adipose layer with its specific morphology. As a result, a thorough constitutive model describing the mechanical behavior of adipose tissue is lacking. This seems odd, because numerical models including the subcutaneous adipose tissue are needed in a wide field of applications such as skin device contact, needle insertion procedures, and understanding deep tissue injuries.© 2008 ASME

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.Copyright

Mechanical Behaviour of the Subcutaneous Fat Layer

A very important function of the human subcutaneous fat layer is to act as a mechanical cushion. However, prolonged loading may result in damage such as pressure ulcers. Depending on the severity and origin of the ulcer, skin, subcutaneous fat and muscle can be affected. The aetiology of pressure ulcers is still poorly understood; it is not even clear whether wounds start to develop in skin, in the fat layer or even in deeper layers [1]. One of the tools used to better understand the way mechanical loading affects tissues is mechanical modeling. The success of a mechanical model strongly depends on the constitutive equations that are used to describe the mechanical properties obtained with experimental work. For skin and muscle much is already known, but a tremendous lack of data is found regarding the properties of adipose tissue. In the case of the subcutaneous fat tissue, very few of the mechanical properties have been determined experimentally.Copyright