In vivo mechanical characterization of arterial wall using an inverse analysis procedure: application on an animal model of intracranial aneurysm.

Intracranial aneurysm is a pathology related to the deterioration of the arterial wall. This work is an essential part of a large-scale project aimed at providing clinicians with a non-invasive patient-specific decision support tool to facilitate the rupture risk assessment. It will lean on the link between the aneurysm shape clinically observed and a database derived from the in vivo mechanical characterization of aneurysms. To supply this database, a deformation device prototype of the arterial wall was developed. Its use coupled with medical imaging (spectral photon-counting computed tomography providing a spatial resolution down to 250 µm) is used to determine the in vivo mechanical properties of the wall based on the inverse analysis of the quantification of the wall deformation observed experimentally. This study presents the in vivo application of this original procedure to an animal model of aneurysm. The mechanical properties of the aneurysm wall identified were consistent with the literature, and the errors between the numerical and experimental results were less than 10%. Based on these parameters, this study allows the assessment of the aneurysm stress state for a known solicitation and points towards the definition of a rupture criterion.

Towards the mechanical characterisation of unruptured intracranial aneurysms: Numerical modelling of interactions between a deformation device and the aneurysm wall.

Intracranial aneurysm is a critical pathology related to the arterial wall deterioration. This work is an essential aspect of a large scale project aimed at providing clinicians with a non-invasive patient-specific decision support tool regarding the rupture risk assessment. A machine learning algorithm links the aneurysm shape observed and a database of UIA clinical images associated with in vivo wall mechanical properties and rupture characterisation. The database constitution is derived from a device prototype coupled with medical imaging. It provides the mechanical characterisation of the aneurysm from the wall deformation obtained by inverse analysis based on the variation of luminal volume. Before performing in vivo tests of the device on small animals, a numerical model was built to quantify the device's impact on the aneurysm wall under natural blood flow conditions. As the clinician will never be able to precisely situate the device, several locations were considered. In preparation for the inverse analysis procedure, artery material laws of increasing complexity were studied (linear elastic, hyper elastic Fung-like). Considering all the device locations and material laws, the device induced relative displacements to the Systole peak (worst case scenario with the highest mechanical stimulus linked to the blood flow) ranging from 375 µm to 1.28 mm. The variation of luminal volume associated with the displacements was between 0.95 % and 4.3 % compared to the initial Systole volume of the aneurysm. Significant increase of the relative displacements and volume variations were found with the study of different cardiac cycle moments between the blood flow alone and the device application. For forthcoming animal model studies, Spectral Photon CT Counting, with a minimum spatial resolution of 250 µm, was selected as the clinical imaging technique. Based on this preliminary study, the displacements and associated volume variations (baseline for inverse analyse), should be observable and exploitable.

Surface wave investigation and phenomenological analysis: Application on in vivo human cutaneous tissue.

The wave phenomenon in free surface media stems from the propagation of mode grouping. Due to the nature of propagation in a given medium, this phenomenon expresses different types of dependence on the medium's properties and represents its mechanical admittance. In contrast with body wave propagation, dependencies related to surface propagation in a medium can be described by spatial-temporal characteristics. These characteristics can be obtained by performing appropriate experiments and do not require prior knowledge of the physical properties of the medium. In this study, we propose an original surface wave investigation and a phenomenological analysis approach adapted to the mechano-bio-structural states evaluation of in vivo human skin. Two objectives are sought with the method proposed: the first concerns the development of a non-invasive device for generating and tracking surface waves in human skin called Free-Skin-Surface-Wave (FSSW); the second concerns the adaptation of the Multi-Chanel Analysis of Surface Waves (MASW) method to evaluate the mechano-bio-structural states of human cutaneous tissue in vivo on the basis of the propagating phenomena observed. As an illustration of the proposed method application, we have done an in vivo evaluation, on intern-forearm of female volunteers population. In addition, we proposed a study of the aging effect and a comparison with ultrasound B-Mode technique, to validate the method sensitivity to follow the mechano-morphological properties of the in vivo human skin. In this study, our medium of application was human skin in vivo, but it is conceivable to extend this application to other soft biological media.

Mechanical and topographical anisotropy for human skin: Ageing effect.

Skin ageing is a complex process which strongly impacts the three skin layers (epidermis, dermis, hypodermis) both functionally and structurally. Of particular interest are the effects of ageing on the dermis biomechanics and how this evolution can impact the reorganization of the cutaneous lines which compose the skin relief. It has been argued that the skin relief could reflect the underlying mechanical condition of the skin. Nevertheless, there is not yet conclusive evidence of the existence of such a link. This work aims at experimentally studying, in vivo, the correlation between the anisotropy of human skin biomechanics and skin topography as a function of ageing. The study was conducted on a panel of 20 men divided into 4 groups according to age (from 23 to 64 years old). The measurements were performed on the right volar forearm of each volunteer. For the biomechanical measurements, an innovative contactless bio-rheometer was developed. It allows access to the mechanical behaviour of the skin in several directions. This device generates an air blast without any contact with the skin area and measures its dynamic response (evaluation of speed of wave propagation) with a linear laser. Moreover, a turntable enables measurements to be made in different angular directions. To analyse the topography of skin relief, we proposed a new method, based on watershed and linear radon transformations. First, an optical analysis of a replica of the skin relief is performed. Then, from the skin image obtained, the density of the cutaneous lines is calculated in different directions using watersheld transformation. The orientation of the detected lines is then estimated with an algorithm based on linear radon transformation. The results observed show a good correlation between the skin relief and the mechanical properties of the skin all along the ageing process. For both topography and mechanical properties, there is a transition from an almost isotropic mechanical behaviour to an anisotropic one as a function of ageing process. Thus, we might conclude that the skin relief reflects the underlying mechanical conditions of the skin.

Biophysical properties of the human finger for touch comprehension: influences of ageing and gender.

The human finger plays an extremely important role in tactile perception, but little is known about how age and gender affect its biophysical properties and their role in tactile perception. We combined studies on contact characteristics, mechanical properties and surface topography to understand age and gender effects on the human finger. The values obtained regarding contact characteristics (i.e. adhesive force) were significantly higher for women than for men. As for mechanical properties (i.e. Young's modulus E), a significant and positive correlation with age was observed and found to be higher for women. A positive correlation was observed between age and the arithmetic mean of surface roughness for men. However, an inverse age effect was highlighted for women. The age and gender effects obtained have never been reported previously in the literature. These results open new perspectives for understanding the weakening of tactile perception across ages and how it differs between men and women.

Study of the tactile perception of bathroom tissues: Comparison between the sensory evaluation by a handfeel panel and a tribo-acoustic artificial finger.

Tactile perception is one of the sensorial modes most stimulated by our daily environment. In particular, perceived softness is an important parameter for judging the sensory quality of surfaces and fabrics. Unfortunately, its assessment greatly depends on the tactile sense of each person, which in turn depends on many factors. Currently, the predominant method for evaluating the tactile perception of fabrics is the human handfeel panel. This qualitative approach does not permit the quantitative measure of touch feel perception. In this study, we present a new artificial finger device to investigate the tactile sensing of ten bathroom tissues. It enables simultaneously measuring the friction and vibrations caused when sliding an artificial finger on the surface of the tissue. The comparison between the results obtained with the artificial finger and the tactile perception evaluated using a handfeel panel showed that the artificial finger is able to separate the two parts of the tactile perception of bathroom tissues: softness and surface texture (velvetiness). The statistical analysis suggests that there is a good correlation between the vibrations measured with the artificial finger and the softness evaluated by the panel. It then shows that the friction measured by the artificial finger is related to the surface texture of a bathroom tissue. The ability of the artificial finger to mimic human touch is demonstrated. Finally, a Principal Component Analysis orders the signatures of the tactile perception of the bathroom tissues in four different groups.

Rheological behaviour of reconstructed skin.

Reconstructed skins have been developed to replace skin when the integrity of tissue has been compromised following severe injury, and to provide alternative methods validating the innocuousness and effectiveness of dermatological and cosmetic products. However the functional properties of tissue substitutes have not been well characterised, mainly since mechanical measurement devices have not been designed to test cell culture materials in vitro. From the mechanical standpoint, reconstructed skin is a heterogeneous multi-layer viscoelastic material. To characterise the time-dependent behaviour of reconstructed skin, spherical indentation load-relaxation tests were performed with a specific original device adapted to measure small soft tissue samples. Load-relaxation indentation tests were performed on a standard reconstructed skin model and on sub-components of the reconstructed skin (3D-scaffold alone and dermal equivalent). Generalised Maxwell and Kelvin-Voigt rheological models are proposed for analysing the mechanical behaviour of each biological tissue. The results indicated a modification of the rheological behaviour of the samples tested as a function of their biological structure. The 3D-scaffold was modelled using the one-branch Maxwell model, while the dermis equivalent and the reconstructed skin were modeled using a one-branch and a two-branch Kelvin-Voigt model, respectively. Finally, we demonstrated that skin cells contribute to global mechanical behaviour through an increase of the instantaneous relaxation function, while the 3D-scaffold alone influences the mechanical response of long relaxation times.

In vivo skin biophysical behaviour and surface topography as a function of ageing.

Normal skin ageing is characterised by an alteration of the underlying connective tissue with measurable consequences on global skin biophysical properties. The cutis laxa syndrome, a rare genetic disorder, is considered as an accelerated ageing process since patients appear prematurely aged due to alterations of dermal elastic fibres. In the present study, we compared the topography and the biomechanical parameters of normal aged skin with an 17 year old cutis laxa patient. Skin topography analyses were conducted on normal skin at different ages. The results indicate that the skin relief highly changes as a function of ageing. The cutaneous lines change from a relatively isotropic orientation to a highly anisotropic orientation. This reorganisation of the skin relief during the ageing process might be due to a modification of the skin mechanical properties, and particularly to a modification of the dermis mechanical properties. A specific bio-tribometer, based on the indentationtechnique under light load, has been developed to study the biophysical properties of the human skin in vivo through two main parameters: the physico-chemical properties of the skin surface, by measuring the maximum adhesion force between the skin and the bio-tribometer; and the bulk mechanical properties. Our results show that the pull-off force between the skin and the biotribometer as well as the skin Young's modulus decrease with age. In the case of the young cutis laxa patient, the results obtained were similar to those observed for aged individuals. These results are very interesting and encouraging since they would allow the monitoring of the cutis laxa skin in a standardised and non-invasive way to better characterize either the evolution of the disease or the benefit of a treatment.

Non contact method for in vivo assessment of skin mechanical properties for assessing effect of ageing.

The assessment of human tissue properties by objective and quantitative devices is very important to improve the understanding of its mechanical behaviour. The aim of this paper is to present a non contact method to measure the mechanical properties of human skin in vivo. A complete non contact device using an air flow system has been developed. Validation and assessment of the method have been performed on inert visco-elastic material. An in vivo study on the forearm of two groups of healthy women aged of 23.2±1.6 and 60.4±2.4 has been performed. Main parameters assessed are presented and a first interpretation to evaluate the reduced Young's modulus is proposed. Significant differences between the main parameters of the curve are shown with ageing. As tests were performed with different loads, the influence of the stress is also observed. We found a reduced Young's modulus with an air flow force of 10 mN of 14.38±3.61 kPa for the youngest group and 6.20±1.45 kPa for the oldest group. These values agree with other studies using classical or dynamic indentation. Non contact test using the developed device gives convincing results.

Interpretation of the human skin biotribological behaviour after tape stripping.

The present study deals with the modification of the human skin biotribological behaviour after tape stripping. The tape-stripping procedure consists in the sequential application and removal of adhesive tapes on the skin surface in order to remove stratum corneum (SC) layers, which electrically charges the skin surface. The skin electric charges generated by tape stripping highly change the skin friction behaviour by increasing the adhesion component of the skin friction coefficient. It has been proposed to rewrite the friction adhesion component as the sum of two terms: the first classical adhesion term depending on the intrinsic shear strength, τ(0), and the second term depending on the electric shear strength, τ(elec). The experimental results allowed to estimate a numerical value of the electric shear strength τ(elec). Moreover, a plan capacitor model with a dielectric material inside was used to modelize the experimental system. This physical model permitted to evaluate the friction electric force and the electric shear strength values to calculate the skin friction coefficient after the tape stripping. The comparison between the experimental and the theoretical value of the skin friction coefficient after the tape stripping has shown the importance of the electric charges on skin biotribological behaviour. The static electric charges produced by tape stripping on the skin surface are probably able to highly modify the interaction of formulations with the skin surface and their spreading properties. This phenomenon, generally overlooked, should be taken into consideration as it could be involved in alteration of drug absorption.

Evaluation of the efficacy of a dill extract in vitro and in vivo.

Lysyl oxidase-like (LOXL) is an extracellular enzyme that catalyses the cross-linking between microfibrils and tropoelastin (TE), thereby ensuring elastic fibre functionality. With ageing, LOXL expression decreases, thus participating in the loss of skin elasticity. In a previous study, we showed that a dill seed extract [INCI name: Peucedanum graveolens (Dill) extract] could increase LOXL expression in cultured dermal fibroblasts. Besides, we showed a good correlation between the measurements of skin elasticity obtained in vitro and in vivo using a fully automated bio-tribometer designed to measure the biomechanical properties of soft and complex materials like skin. The aim of this study was to evaluate the ability of the dill extract to improve skin elasticity in vitro and in vivo using different models. Using the bio-tribometer, we first showed that the lateral elasticity of dermis equivalents (DEs) treated with the dill extract at 1% was significantly increased by +29% (P < 0.01) when compared to untreated DEs. In vivo, skin firmness and elastic recovery measured using cutometry methods were also significantly improved compared to placebo in volunteers treated for 56 days with a formula containing 1% of dill extract. Moreover, the clinical evaluation evidenced significant improvements in 'skin elasticity' compared to placebo. A majority of subjects treated with the dill extract also noted significant improvements in skin elasticity, firmness and slackness of the jaw line. Finally, mean wrinkle area and length were also significantly reduced compared to placebo after 84 days as measured using silicone replicas taken from the crow's feet. In summary, this study showed that the dill extract could improve elasticity of DEs in vitro as well as skin biomechanical properties and appearance in vivo. It also highlights the relevance of using the bio-tribometer as an exploratory tool for the measurement of skin elasticity in vitro.

Characterization of the mechanical properties of a dermal equivalent compared with human skin in vivo by indentation and static friction tests.

BACKGROUND/AIMS: The study of changes in skin structure with age is becoming all the more important with the increase in life. The atrophy that occurs during aging is accompanied by more profound changes, with a loss of organization within the elastic collagen network and alterations in the basal elements. The aim of this study is to present a method to determine the mechanical properties of total human skin in vivo compared with dermal equivalents (DEs) using indentation and static friction tests. METHODS: A new bio-tribometer working at a low contact pressure for the characterization the mechanical properties of the skin has been developed. This device, based on indentation and static friction tests, also allows to characterize the skin in vivo and reconstructed DEs in a wide range of light contact forces, stress and strain. RESULTS: This original bio-tribometer shows the ability to assess the skin elasticity and friction force in a wide range of light normal load (0.5-2 g) and low contact pressure (0.5-2 kPa). The results obtained by this approach show identical values of the Young's modulus E(*) and the shear modulus G(*) of six DEs obtained from a 62-year-old subject (E(*)=8.5+/-1.74 kPa and G(*)=3.3+/-0.46 kPa) and in vivo total skin of 20 subjects aged 55 to 70 years (E(*)=8.3+/-2.1 kPa, G(*)=2.8+/-0.8 kpa).

A new approach to describe the skin surface physical properties in vivo.

In the present paper, we describe a new mechanical method characterising the physico-chemical properties of human skin and their variations along with liquid exposure scenario to the skin surface. A specific bio-tribometer has been developed to study the physical properties of the skin in vivo by measuring the maximum adhesion force between the skin and the bio-tribometer. We showed that the lipidic film present on skin surface was responsible for skin adhesion due to capillary phenomena. The measure of pull-off force between skin and bio-tribometer has permitted to estimate the liquid/vapour surface tension of the lipidic film (gamma(LV) approximately 6.3mJ/m(2) in 30-year-old volunteer). The kinetic of sorption/desorption (sorption means indifferently adsorption and absorption process) of distilled water from the skin has been observed through the variation of the indenter/skin pull-off force versus time after distilled water application to the skin surface. This permits to follow in real time the variation of the skin physico-chemical properties after liquid application onto the skin surface. Finally, the increasing of skin friction coefficient after distilled water application onto skin surface was explained by the capillary adhesion force between the probe and the skin.

In vivo measurements of the elastic mechanical properties of human skin by indentation tests.

Knowledge about the human skin mechanical properties is essential in several domains, particularly for dermatology, cosmetic or to detect some cutaneous pathology. This study proposes a new method to determine the human skin mechanical properties in vivo using the indentation test. Usually, the skin mechanical parameters obtained with this method are influenced by the mechanical properties of the subcutaneous layers, like muscles. In this study, different mechanical models were used to evaluate the effect of the subcutaneous layers on the measurements and to extract the skin elastic properties from the global mechanical response. The obtained results demonstrate that it is necessary to take into account the effect of the subcutaneous layers to correctly estimate the skin Young's modulus. Moreover, the results illustrate that the variation of the measured Young's modulus at low penetration depth cannot be correctly described with usual one-layer mechanical models. Thus a two-layer elastic model was proposed, which highly improved the measurement of the skin mechanical properties.