Håvar Junker

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Junker

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Håvar

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0000-0001-7503-3614

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Publications 1 - 5 of 5

A quantitative comparison of devices for in vivo biomechanical characterization of human skin
Junker, Håvar; Thumm, Bettina; Halvachizadeh, Sascha; et al. (2023)
Mechanics of Soft Materials
Non-invasive skin characterization devices are emerging as a valuable tool in clinical skin research. In recent years, the range of available experimental techniques and methods used to determine the biomechanical properties of skin has increased considerably. Although a substantial amount of work has been devoted to assessing the working principle of macroscopic skin characterization devices individually, a rationalization and comparison between them is still lacking. This motivated the present study, which aimed to characterize and compare three commonly used working principles: suction, dynamic shear loading, and indentation. A synthetic model system with tunable mechanical properties was used to assess the three devices, and the results rationalized based on corresponding finite element models. In vivo measurements were performed on healthy volunteers to investigate the capability of differentiating the biomechanical properties of skin at different body locations, and to assess the intra- and inter-rater reliability of each device. The present comparative analysis indicates that the analyzed functional principles perceive the stiffness of human skin differently, with relevant implications for the interpretation of the respective measurement results.
Biomechanical and biochemical changes in murine skin during development and aging
Martyts, Anastasiya; Sachs, David; Hiebert, Paul; et al. (2024)
Acta Biomaterialia
Aging leads to biochemical and biomechanical changes in skin, with biological and functional consequences. Despite extensive literature on skin aging, there is a lack of studies which investigate the maturation of the tissue and connect the microscopic changes in the skin to its macroscopic biomechanical behavior as it evolves over time. The present work addresses this knowledge gap using multiscale characterization of skin in a murine model considering newborn, adult and aged mice. Monotonic uniaxial loading, tension relaxation with change of bath, and loading to failure tests were performed on murine skin samples from different age groups, complemented by inflation experiments and atomic force microscopy indentation measurements. In parallel, skin samples were characterized using histological and biochemical techniques to assess tissue morphology, collagen organization, as well as collagen content and cross-linking. We show that 1-week-old skin differs across nearly all measured parameters from adult skin, showing reduced strain stiffening and tensile strength, a thinner dermis, lower collagen content and altered crosslinking patterns. Surprisingly, adult and aged skin were similar across most biomechanical parameters in the physiologic loading range, while aged skin had lower tensile strength and lower stiffening behavior at large force values. This correlates with altered collagen content and cross-links. Based on a computational model, differences in mechanocoupled stimuli in the skin of the different age groups were calculated, pointing to a potential biological significance of the age-induced biomechanical changes in regulating the local biophysical environment of dermal cells. Statement of significance: Skin microstructure and the emerging mechanical properties change with age, leading to biological, functional and health-related consequences. Despite extensive literature on skin aging, only very limited quantitative data are available on microstructural changes and the corresponding macroscopic biomechanical behavior as they evolve over time. This work provides a wide-range multiscale mechanical characterization of skin of newborn, adult and aged mice, and quantifies microstructural correlations in tissue morphology, collagen content, organization and cross-linking. Remarkably, aged skin retained normal hydration and normal biomechanical function in the physiological loading range but showed significantly reduced properties at super-physiological loading. Our data show that age-related microstructural differences have a profound effect not only on tissue-level properties but also on the cell-level biophysical environment.
Multiscale mechanics of skin
Junker, Håvar (2024)
As one of the largest organs in the human body, the skin constitutes our primary structural and chemical barrier against influence from the surroundings. In our daily lives, the skin plays an important role in the hydration and temperature regulation of our bodies, in addition to protecting the deeper tissues of the body from harmful UV-radiation. From a mechanical perspective, skin is a fascinating material, exhibiting strongly nonlinear strain-stiffening behavior in addition to a remarkable tear resistance. The multi-faceted role of the skin can be attributed to its complex microstructure. Broadly speaking, skin can be divided into three main layers; the epidermis, the dermis and the hypodermis. The epidermis, the outermost layer of the skin, constitutes the primary barrier function through a tightly packed arrangement of keratinocyte cells. The main load-bearing capacities of the skin are typically attributed to the dermis, in which the reticular structure is composed of a complex network of collagen and elastin fibers, maintained by the residing fibroblast cells. Ultimately, the hypodermis is mainly composed of fat tissue, and serves the role of protecting the underlying tissue against impact as well as important functions for energy storage and temperature regulation. In this thesis, experiments at different length-scales are combined with computational modeling to enhance the understanding of the mechanical behavior of skin. It is now well-established that the homeostasis of skin functions in a fine interplay between mechanical and chemical cues. Furthermore, the mechanobiology of skin has been documented to be highly relevant for a wide range of conditions such as skin fibrosis, the healing of skin wounds and skin growth. In the first part of the thesis, the biomechanical properties of skin are assessed on the tissue length-scale using noninvasive biomechanical skin characterization devices. Although a variety of different functional principles are used in the assessment of skin, few quantitative comparisons between different principles have been done. Herein, three commonly used functional principles, suction, dynamic shear load and indentation, are analyzed. Preliminary measurements on synthetic materials allowed to rationalize the different principles, indicating a similar capability of detecting changes in the underlying substrate stiffness between the devices. Measurements on healthy human volunteers reveals a similar tendency to detect differences in apparent stiffness between different body locations, albeit with large differences in the reliability between the different principles, which is devoted to the influence from boundary conditions. Ultimately, an inverse finite element model is used to rationalize the results, with important implications for the interpretation of the measurement results. In the second part, the mechanical properties of skin are investigated on the local length-scale. First, murine excisional wounds are assessed with atomic force microscopy based indentation tests to resolve previously reported conflicting findings on the mechanical behavior of healing skin wounds. When comparing the apparent stiffness of different regions in the wound, large differences are documented. In line with previous findings, the apparent stiffness of the newly forming tissue is documented to be significantly lower than the healthy tissue. In particular, the present work identifies the hyperproliferative epithelium, a cellular layer forming during the initial phases of wound healing, as a potential provider of structural integrity to the wound. Measurements on wounds from later time points identify the healing progression of the tissue. To assess the influence from local topography on the apparent stiffness in the different material regions, topographic information obtained from atomic force microscopy imaging is implemented in a bi-phasic material model. Next, the influence of intrinsic ageing on the biomechanical properties of skin are assessed in murine tissue. Considering baby, adult and very old mice with atomic force microscopy based indentation tests, significant differences between the baby and adult animals are documented. Comparison with uniaxial tension experiments at the tissue length-scale reveal that very young and very old skin respond differently to hyper-physiological loading. Ultimately, the development and proof-of-concept of an in vivo stretching device is presented. Motivated by typical discrepanices of several orders of magnitude when comparing experimental results from different length-scales, a protocol to preserve tissue stretch during the preparation of tissue for local indentation tests is presented. When comparing the apparent modulus from stretched and unstretched samples, a significant increase is documented.
Collagen hydrogels with similar polymer content but different microstructure — A comparative analysis of mechanical response
Busenhart, Kim; Brun, Julie; Junker, Håvar; et al. (2025)
Journal of the Mechanical Behavior of Biomedical Materials
Understanding the mechanical properties of collagen hydrogels is essential for successful applications in tissue engineering and 3D cell culture. This study compares the mechanical behavior of two collagen hydrogel sheets with similar collagen content but different microstructures. One of the differences is that one gel is isotropic while the other has collagen fibers oriented towards the sheet's plane. Experiments were performed at macro- (uniaxial tension in the sheet plane) and micro-length scale (AFM-based indentation perpendicular to the plane), and a discrete network model was developed to rationalize the observed differences. The experiments showed an order of magnitude difference in the uniaxial stiffness of the two gels. The softer gel exhibited near-incompressible behavior, while the stiffer gel showed a highly contractile response, with Poisson's ratios around 8. Conversely, the apparent modulus from nano-indentation showed an opposite trend, with higher local stiffness for the gel that was softer in uniaxial tests. The computational model represents the material using a network of bi-linear connectors for the fibrous component and a compressible neo-Hookean material for the surrounding water-rich matrix, assumed to form due to interactions between collagen and water. Under the constraint of equal collagen content, model parameters were tuned to reproduce the observed response of both materials, considering the observed differences in fiber diameter. Importantly, the computations indicate that the difference in collagen orientation cannot explain the observed differences between the mechanical responses of the gels. Successful scaling between the two gels depends on the assumption that, due to their crimped initial state individual fibers primarily experience bending rather than tension when the material is stretched. Moreover, high tensile stretch of the fibers is shown to elicit large lateral contraction. Overall, the results demonstrate the wide range of mechanical properties displayed by hydrogels with similar collagen content, which can be rationalized using discrete models representative of their microstructure.
Characterization of murine excisional wounds based on atomic force microscopy indentation
Junker, Håvar; Wahlsten, Adam; Hopf, Raoul; et al. (2025)
Acta Biomaterialia
Murine excisional skin wounds represent a widely applied model to investigate factors influencing the healing process. Among those, mechanical factors are receiving increasing attention, for instance concerning the role of fibroblasts’ activation in contracting the wound and forming a fibrotic scar. Atomic Force Microscopy (AFM) represents a useful tool for the mechanical characterization of biological tissues at the micrometer length scale. We recently used AFM indentation to characterize healthy murine dermis for animals of different ages. In this study, we performed AFM-based indentation on different regions of a wound and the adjacent unwounded skin at two time points of the healing process, i.e. during new tissue formation (day 7 after wounding) and early remodeling (day 14). Data analysis of the earlier time point indicates that the hyperproliferative epithelium is much stiffer than the underlying regions of the granulation tissue and the latter are softer than adjacent skin. These differences are reduced at the later time point. Different stiffness measures are extracted from the data and compared in their capability of discriminating between tissue regions. A finite element analysis of the indentation experiments implementing a biphasic constitutive model was performed to investigate the influence of constitutive model parameters and surface roughness. Compared to the conventional readout of AFM measurements, which assumes that tissues behave as incompressible linear elastic materials, the shear stiffness can be up to 50 % higher. Simulation of the local topography, quantified using AFM contact mode imaging, showed that local stiffness may be underestimated by up to 50 % due to surface roughness. The present data and protocol can be used in future studies for a quantitative investigation of mechanobiological factors influencing physiology and pathology of wound healing. Statement of significance: The healing of tissue injuries, in particular skin wounds, places a substantial burden on the global health care system. Although it is widely accepted that the local mechanical environment of the extracellular matrix represents an important aspect of the tissue repair process, its quantitative characterization during the course of healing is largely incomplete. In this study, we use AFM-based indentation to map the mechanical properties of structural compartments in a healing skin wound at two timepoints. Our results pinpoint key differences between relevant compartments, resolving previously reported contradictions on the deformability of wounds, and providing important insights for mechanobiological studies. Furthermore, we rationalize the influence of different parameters, including the surface topography, using a bi-phasic computational model. The results have general implications for the interpretation of force-indentation data widely used to characterize biological materials.

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Håvar Junker

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