Biaxial mechanics of thermally denaturing skin - Part 1: Experiments

The mechanics of collagenous soft tissues, such as skin, are sensitive to heat. Thus, quantifying and modeling thermo-mechanical coupling of skin is critical to our understanding of skin's physiology, pathophysiology, and its treatment. However, key gaps persist in our knowledge about skin's coupled thermo-mechanics. Among them, we haven't quantified the role of skin's microstructural organization in its response to superphysiological loading. To fill this gap, we conducted a comprehensive set of experiments in which we combined biaxial mechanical testing with histology and two-photon imaging under liquid heat treatment at temperatures ranging from 37^∘C to 95^∘C lasting between 2 seconds and 5 minutes. Among other observations, we found that unconstrained skin, when exposed to high temperatures, shrinks anisotropically with the principal direction of shrinkage being aligned with collagen's principal orientation. Additionally, we found that when skin is isometrically constrained, it produces significant forces during denaturation that are also anisotropic. Finally, we found that denaturation significantly alters the mechanical behavior of skin. For short exposure times, this alteration is reflected in a reduction of stiffness at high strains. At long exposure times, the tissue softened to a point where it became untestable. We supplemented our findings with confirmation of collagen denaturation in skin via loss of birefringence and second harmonic generation. Finally, we captured all time-, temperature-, and direction-dependent experimental findings in a hypothetical model. Thus, this work fills a fundamental gap in our current understanding of skin thermo-mechanics and will support future developments in thermal injury prevention, thermal injury management, and thermal therapeutics of skin. STATEMENT OF SIGNIFICANCE: Our work experimentally explores how skin reacts to being heated. That is, it measures how much skin shrinks, what forces it produces, and how its mechanical properties change; all as a function of temperature, but also of direction and time. Additionally, our work connects these measurements to changes in skin's microscopic make-up. This knowledge is important to our understanding of skin's function and dysfunction, especially during burn injuries or heat-dependent treatments.