Substantial research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, affects fundamental cellular processes, including spreading, growth, proliferation, migration, differentiation and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins are widely used to assess the role of stiffness, and results from such experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo. However, tissues and ECMs are not linearly elastic materials-they exhibit far more complex mechanical behaviours, including viscoelasticity (a time-dependent response to loading or deformation), as well as mechanical plasticity and nonlinear elasticity. Here we review the complex mechanical behaviours of tissues and ECMs, discuss the effect of ECM viscoelasticity on cells, and describe the potential use of viscoelastic biomaterials in regenerative medicine. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and can promote behaviours that are not observed with elastic hydrogels in both two- and three-dimensional culture microenvironments. These findings have provided insights into cell-matrix interactions and how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results suggest design guidelines for the next generation of biomaterials, with the goal of matching tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.

Effects of extracellular matrix viscoelasticity on cellular behaviour.

In this review, we discuss the current knowledge on the tribology of human skin and present an analysis of the available experimental results for skin friction coefficients. Starting with an overview on the factors influencing the friction behaviour of skin, we discuss the up-to-date existing experimental data and compare the results for different anatomical skin areas and friction measurement techniques. For this purpose, we also estimated and analysed skin contact pressures applied during the various friction measurements. The detailed analyses show that substantial variations are a characteristic feature of friction coefficients measured for skin and that differences in skin hydration are the main cause thereof, followed by the influences of surface and material properties of the contacting materials. When the friction coefficients of skin are plotted as a function of the contact pressure, the majority of the literature data scatter over a wide range that can be explained by the adhesion friction model. The case of dry skin is reflected by relatively low and pressure-independent friction coefficients (greater than 0.2 and typically around 0.5), comparable to the dry friction of solids with rough surfaces. In contrast, the case of moist or wet skin is characterised by significantly higher (typically >1) friction coefficients that increase strongly with decreasing contact pressure and are essentially determined by the mechanical shear properties of wet skin. In several studies, effects of skin deformation mechanisms contributing to the total friction are evident from friction coefficients increasing with contact pressure. However, the corresponding friction coefficients still lie within the range delimited by the adhesion friction model. Further research effort towards the analysis of the microscopic contact area and mechanical properties of the upper skin layers is needed to improve our so far limited understanding of the complex tribological behaviour of human skin.

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Tribology of Skin: Review and Analysis of Experimental Results for the Friction Coefficient of Human Skin

In vivo mechanical characterization of human liver.

On the viscoelastic character of liver tissue: experiments and modelling of the linear behaviour.

A three-dimensional nonlinear model for dissipative response of soft tissue

This paper reports on the initial stages of a project to simulate the nonlinear mechanical behavior of an aging human face. A cross-section of the facial structure is considered to consist of a multilayered composite of tissues with differing mechanical behavior. The constitutive properties of these tissues are incorporated into a finite element model of the three-dimensional facial geometry. Relatively short time (elastic-viscoplastic) behavior is governed by equations previously developed which are consistent with mechanical tests. The long time response is controlled by the aging elastic components of the tissues. An aging function is introduced which, in a simplified manner, captures the observed loss of stiffness of these aging elastic components due to the history of straining as well as other physiological and environmental influences. Calculations have been performed for 30 years of exposure to gravitational forces. Progressive gravimetric soft tissue descent is simulated, which is regarded as the main indication of facial aging. Results are presented for the deformations and stress distributions in the layers of the soft tissues.

/pdf/nonlinear-elastic-viscoplastic-constitutive-equations-for-4dwsioij1z.pdf

Nonlinear elastic-viscoplastic constitutive equations for aging facial tissues.

Unified constitutive equations for elastic-viscoplastic materials were modified and used to model the highly nonlinear elastic and rate-dependent inelastic response exhibited in recent experiments on excised facial tissues. These included the skin and the underlying supportive tissue SMAS (the Superficial Musculoaponeurotic System). This study indicates a number of relevant results: The skin is more strain rate dependent than the SMAS; the nonlinearity of the elasticity of the skin is greater than that of the SMAS ; both tissues exhibit a hardening effect indicated by increased resistance to inelastic deformation due to stress acting over a time period; the hardening effect leads to a decrease in time dependence and an increased elastic range, which is more pronounced for SMAS. Consequently, the SMAS can be viewed as the firmer elastic foundation of the more viscous skin. Moreover, the relaxation time for the skin is fairly, short so the skin would be expected to conform to the deformation of the SMAS if it remained attached to the SMAS during stretching. This is relevant when it is undesirable to separate the skin from the SMAS for physiological reasons.

An Elastic–Viscoplastic Model for Excised Facial Tissues

A three-dimensional finite element program is described which attempts to simulate the nonlinear mechanical behavior of an aging human face with specific reference to progressive gravimetric soft tissue descent. A cross section of the facial structure is considered to consist of a multilayered composite of tissues with differing mechanical behavior. Relatively short time (elastic-viscoplastic) behavior is governed by equations previously developed which are consistent with mechanical tests. The long time response is controlled by the aging elastic components of the tissues. An aging function is introduced which, in a simplified manner, models the observed loss of stiffness of these aging elastic components due to the history of straining as well as other physiological and environmental influences. Calculations have been performed for 30 years of exposure to gravitational forces. The deformations and stress distributions in the layers of the soft tissues are described. Overall, the feasibility of using constitutive relations which reflect the highly nonlinear elastic-viscoplastic behavior of facial soft tissues in finite element based three-dimensional mechanical analyses of the human face is demonstrated. Further developments of the program are discussed in relation to possible clinical applications. Although the proposed aging function produces physically reasonable long-term response, experimental data are not yet available for more quantitative validation.

N. S. Binur

Papers

Nonlinear elastic-viscoplastic constitutive equations for aging facial tissues.

An Elastic–Viscoplastic Model for Excised Facial Tissues

Simulation of the aging face.