The biomechanics of wounds at physiologically relevant levels: Understanding skin's stress-shielding effect for the quantitative assessment of healing.

Wounds are responsible for the decrease in quality of life of billions of people around the world. Their assessment relies on subjective parameters which often delays optimal treatments and results in increased healthcare costs. In this work, we sought to understand and quantify how wounds at different healing stages (days 1, 3, 7 and 14 post wounding) change the mechanical properties of the tissues that contain them, and how these could be measured at clinically relevant strain levels, as a step towards quantitative wound tracking technologies. To achieve this, we used digital image correlation and mechanical testing on a mouse model of wound healing to map the global and local tissue strains. We found no significant differences in the elastic and viscoelastic properties of wounded vs unwounded skin when samples were measured in bulk, presumably as these were masked by the protective mechanisms of skin, which redistributes the applied loads to mitigate high stresses and reduce tissue damage. By measuring local strain values and observing the distinct patterns they formed, it was possible to establish a connection between the healing phase of the tissue (determined by the time post-injury and the observed histological features) and the overall mechanical behaviour. Importantly, these parameters were measured from the surface of the tissue, using physiologically relevant strains without increasing the tissue's damage. Adaptations of these approaches for clinical use have the potential to aid in the identification of skin healing problems, such as excessive inflammation or lack of mechanical progression over time. An increase, decrease, or lack of change in the elasticity and viscoelasticity parameters, can be indicative of wound state, thus ultimately leading to improved diagnostic outcomes.

Rapid mechanosensitive migration and dispersal of newly divided mesenchymal cells aid their recruitment into dermal condensates.

Embryonic mesenchymal cells are dispersed within an extracellular matrix but can coalesce to form condensates with key developmental roles. Cells within condensates undergo fate and morphological changes and induce cell fate changes in nearby epithelia to produce structures including hair follicles, feathers, or intestinal villi. Here, by imaging mouse and chicken embryonic skin, we find that mesenchymal cells undergo much of their dispersal in early interphase, in a stereotyped process of displacement driven by 3 hours of rapid and persistent migration followed by a long period of low motility. The cell division plane and the elevated migration speed and persistence of newly born mesenchymal cells are mechanosensitive, aligning with tissue tension, and are reliant on active WNT secretion. This behaviour disperses mesenchymal cells and allows daughters of recent divisions to travel long distances to enter dermal condensates, demonstrating an unanticipated effect of cell cycle subphase on core mesenchymal behaviour.