Biomechanical and biochemical changes in murine skin during development and aging.

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.

A quantitative comparison of devices for in vivo biomechanical characterization of human skin.

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.