Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

Collagen and elastin networks make up the majority of the extracellular matrix in many organs, such as the skin. The mechanisms which are involved in the maintenance of homeostatic equilibrium of these networks are numerous, involving the regulation of genetic expression, growth factor secretion, signalling pathways, secondary messaging systems, and ion channel activity. However, many factors are capable of disrupting these pathways, which leads to an imbalance of homeostatic equilibrium. Ultimately, this leads to changes in the physical nature of skin, both functionally and cosmetically. Although various factors have been identified, including carcinogenesis, ultraviolet exposure, and mechanical stretching of skin, it was discovered that many of them affect similar components of regulatory pathways, such as fibroblasts, lysyl oxidase, and fibronectin. Additionally, it was discovered that the various regulatory pathways intersect with each other at various stages instead of working independently of each other. This review paper proposes a model which elucidates how these molecular pathways intersect with one another, and how various internal and external factors can disrupt these pathways, ultimately leading to a disruption in collagen and elastin networks.

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Molecular Mechanisms of Stress-Responsive Changes in Collagen and Elastin Networks in Skin

Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis...

Wound Healing: A Cellular Perspective.

Wearable sensors have recently seen a large increase in both research and commercialization. However, success in wearable sensors has been a mix of both progress and setbacks. Most of commercial progress has been in smart adaptation of existing mechanical, electrical and optical methods of measuring the body. This adaptation has involved innovations in how to miniaturize sensing technologies, how to make them conformal and flexible, and in the development of companion software that increases the value of the measured data. However, chemical sensing modalities have experienced greater challenges in commercial adoption, especially for non-invasive chemical sensors. There have also been significant challenges in making significant fundamental improvements to existing mechanical, electrical, and optical sensing modalities, especially in improving their specificity of detection. Many of these challenges can be understood by appreciating the body's surface (skin) as more of an information barrier than as an information source. With a deeper understanding of the fundamental challenges faced for wearable sensors and of the state-of-the-art for wearable sensor technology, the roadmap becomes clearer for creating the next generation of innovations and breakthroughs.

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Wearable sensors: modalities, challenges, and prospects

The mechanical properties of skin are important for a number of applications including surgery, dermatology, impact biomechanics and forensic science. In this study, we have investigated the influence of location and orientation on the deformation characteristics of 56 samples of excised human skin. Uniaxial tensile tests were carried out at a strain rate of 0.012 s(-1) on skin from the back. Digital Image Correlation was used for 2D strain measurement and a histological examination of the dermis was also performed. The mean ultimate tensile strength (UTS) was 21.6±8.4 MPa, the mean failure strain 54%±17%, the mean initial slope 1.18±0.88 MPa, the mean elastic modulus 83.3±34.9 MPa and the mean strain energy was 3.6±1.6 MJ/m(3). A multivariate analysis of variance has shown that these mechanical properties of skin are dependent upon the orientation of the Langer lines (P<0.0001-P=0.046). The location of specimens on the back was also found to have a significant effect on the UTS (P=0.0002), the elastic modulus (P=0.001) and the strain energy (P=0.0052). The histological investigation concluded that there is a definite correlation between the orientation of the Langer lines and the preferred orientation of collagen fibres in the dermis (P<0.001). The data obtained in this study will provide essential information for those wishing to model the skin using a structural constitutive model.

https://researchrepository.ucd.ie/bitstream/10197/4616/2/Repos%20-%20not-%20commented2%20done.pdf

Characterization of the anisotropic mechanical properties of excised human skin

Background/aims: The purpose of this work is to attempt to determine the elastic spring constant for collagen and elastic fibers (elastin) in skin and to detemine if the values of these elastic constants are similar to those reported for other tissues.

Methods: We studied the viscoelastic mechanical properties of human skin and dermis by measuring the incremental stress-strain behavior. Elastic stress-strain curves were used to obtain the elastic spring constant of elastin and collagen while the collagen fibril length was obtained from the slope of viscous stress-strain curves.

Results: Our results suggest that the elastic spring constant for elastin is about 4.0 MPa while that for collagen is about 4.4 GPa. The former value is similar to that calculated for ligamentum nuchae while the latter value is about 70% of the value found for tendon and self-assembled type I collagen fibers. The differences between the elastic constants for collagen molecules in tendon and skin is hypothesized to reflect the higher molecular tilt angle and lower D period found in skin compared to tendon as well as a shorter fibril length.

Conclusion: The differences in the collagen types present in skin and tendon may influence collagen self-assembly and the resulting viscoelastic properties.

Viscoelastic properties of human skin and processed dermis.

We have studied the strain-rate dependency of the viscoelastic mechanical properties of human dermis from young (23-year-old) and old (87-year-old) donors using incremental stress–strain measurements. The elastic spring constant for elastic fibers was found to be strain-rate and age dependent, whereas that for collagen was only age dependent. Fibril lengths were observed to decrease with increased strain rates and age for both elastic and collagen fibers; however, the large decrease in collagen fibril viscosity was hypothesized to be a result of thixotropy that results when neighboring collagen fibrils slide by each other. It is concluded that the elastic spring constant measured for elastic fibers may be higher than previously reported and is consistent with stretching of α-helical segments of elastin into a more extended conformation during the initial part of the elastic stress–strain curve. The decrease in the elastic spring constant with increased age observed is consistent with disruption of the elastic fibers and loss of α-helical structure. The pH dependency of the elastic modulus reported previously for collagen suggests that charge–charge interactions within and between collagen molecules are involved in energy storage during stretching. Elastic energy storage is consistent with the stretching of charged pairs located in flexible regions of the collagen molecule. Shear thinning, or thixotropy of skin, is hypothesized to reflect breakage of bonds that occur between collagen fibrils. It is hypothesized that both collagen and elastin are complex macromolecules that are hybrids of flexible and rigid regions. The flexible regions reversibly store elastic energy during stretching by breakage of secondary bonds. After stretching, the flexible regions become extended and transfer stress to the rigid regions of these molecules. This prevents premature mechanical failure of collagen and elastic fibers in the dermis. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1978–1985, 2002

Viscoelastic properties of young and old human dermis: A proposed molecular mechanism for elastic energy storage in collagen and elastin

Mechanical forces play a role in the development and evolution of extracellular matrices (ECMs) found in connective tissue. Gravitational forces acting on mammalian tissues increase the net muscle forces required for movement of vertebrates. As body mass increases during development, musculoskeletal tissues and other ECMs are able to adapt their size to meet the increased mechanical requirements. However, the control mechanisms that allow for rapid growth in tissue size during development are altered during maturation and aging. The purpose of this mini-review is to examine the relationship between mechanical loading and cellular events that are associated with downregulation of mechanochemical transduction, which appears to contribute to aging of connective tissue. These changes result from decreases in growth factor and hormone levels, as well as decreased activation of the phosphorelay system that controls cell division, gene expression, and protein synthesis. Studies pertaining to the interactions among mechanical forces, growth factors, hormones, and their receptors will better define the relationship between mechanochemical transduction processes and cellular behavior in aging tissues.

Invited Review: Role of mechanophysiology in aging of ECM: effects of changes in mechanochemical transduction

Measurement of the mechanical properties of skin in vivo has been complicated by the lack of methods that can accurately measure the viscoelastic properties without assuming values of Poisson's ratio and tissue density. In this paper, we present the results of preliminary studies comparing the mechanical properties of skin and scar tissue measured using a technique involving optical cohesion tomography (OCT) and vibrational analysis. This technique has been reported to give values of the modulus that correlate with those obtained from tensile measurements made on decellularized dermis (Shah et al., Skin Res Technol 2016;23:399-406; Shah et al., J Biomed Mater Res Part 2017;105:15-22). The high correlation between moduli measured using vibrational studies and uniaxial tensile tests suggest that the modulus can be determined by measuring the natural frequency that occurs when a tissue is vibrated in tension. The results of studies on glutaric anhydride treated decellularized dermis suggest that vibrational analysis is a useful technique to look at changes in the properties of skin that occur after cosmetic and surgical treatments are used. Preliminary results suggest that the resonant frequency of scar tissue is much higher than that of adjacent normal skin reflecting the higher collagen content of scar. OCT in concert with vibrational analysis appears to be a useful tool to evaluate processes that alter skin properties in animals and humans as well to study the onset and pathogenesis of skin diseases such as cancer. This technique may be useful to evaluate the extent of wound healing in skin diabetic ulcers and other chronic skin conditions, scar tissue formation in response to implants, and other therapeutic treatments that alter skin properties. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1421-1427, 2018.

Biomechanical analysis of decellularized dermis and skin: Initial in vivo observations using optical cohesion tomography and vibrational analysis

Several new methods have been used to non-destructively evaluate the mechanical properties of materials and tissues including magnetic resonance elastography, ultrasound elastography, optical coherence elastography, and various forms of vibrational analysis. One of the limitations of using these methods is the need to establish a relationship between the modulus measured using each new technique and moduli measured using well-established techniques such as constant rate-of-strain and incremental stress-strain curves. In addition, there are no available methods for analyzing the mechanical properties of the individual components of multi-component materials. In this article, we present data showing that there is a strong correlation (correlation coefficient >0.9) between the modulus measured using classical uniaxial tensile incremental stress-strain tests and those made using a combination of optical coherence tomography and vibrational analysis. Beyond this, we demonstrate that the moduli of the major structural components of pig skin can be measured using this technique. These results suggest that optical coherence tomography in concert with vibrational analysis can be used to measure the moduli of biological and implant materials without having to determine Poisson's ratio. In addition, each of the moduli of the major fibrous components of pig skin can be measured concurrently using this technique. These results may be useful in the characterization of synthetic implants and tissue derived materials without requiring removal of one or more components that are to be characterized. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1666-1671, 2017.

Dale DeVore

Papers

Viscoelastic properties of human skin and processed dermis.

Viscoelastic properties of young and old human dermis: A proposed molecular mechanism for elastic energy storage in collagen and elastin

Invited Review: Role of mechanophysiology in aging of ECM: effects of changes in mechanochemical transduction

Biomechanical analysis of decellularized dermis and skin: Initial in vivo observations using optical cohesion tomography and vibrational analysis

Vibrational analysis of implants and tissues: Calibration and mechanical spectroscopy of multi-component materials