Biology subjects

Meador, W. D.

Publications and source records attributed to Meador, W. D..

3 recordsLinked to original sources

bioRxiv2021

The biaxial mechanics of thermally denaturing skin - Part I: Experiments

The mechanics of collageneous soft tissues, such as skin, are sensitive to heat. Thus, quantifying and modeling thermo-mechanical coupling of skin is critical to our understanding of skins physiology, pathophysiology, as well as its treatment. However, key gaps persist in our knowledge about skins coupled thermo-mechanics. Among them, we havent quantified the role of skins 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. Among other observations, we found that unconstrained skin, when exposed to high temperatures, shrinks anisotropically with the principle direction of shrinkage being aligned with collagens principle orientation. Additionally, we found that when skin is isometrically constrained, it produces significant forces during denaturing 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.

bioengineering↗

bioRxiv2021

The biaxial mechanics of thermally denaturing skin - Part II: Modeling

Understanding the response of skin to superphysiological temperatures is critical to the diagnosis and prognosis of thermal injuries, and to the development of temperature-based medical therapeutics. Unfortunately, this understanding has been hindered by our incomplete knowledge about the nonlinear coupling between skin temperature and its mechanics. In Part I of this study we experimentally demonstrated a complex interdependence of time, temperature, direction, and load in skins response to superphysiological temperatures. In Part II of our study, we test two different models of skins thermo-mechanics to explain our observations. In both models we assume that skins response to superphysiological temperatures is governed by the denaturation of its highly collageneous microstructure. Thus, we capture skins native mechanics via a microstructurally-motivated strain energy function which includes probability distributions for collagen fiber orientation and waviness. In the first model, we capture skins response to superphysiological temperatures as a transition between two states that link the kinetics of collagen fiber denaturation to fiber coiling and to the transformation of each fibers constitutive behavior from purely elastic to viscoelastic. In the second model, we capture skins response to super-physiological temperatures instead via three states in which a sequence of two reactions link the kinetics of collagen fiber denaturation to fiber coiling, followed by a state of fiber damage. Given the success of both models in qualitatively capturing our observations, we expect that our work will provide guidance for future experiments that could probe each models assumptions toward a better understanding of skins coupled thermo-mechanics and that our work will be used to guide the engineering design of heat treatment therapies.

biophysics↗

bioRxiv2020

The tricuspid valve also maladapts: A multiscale study in sheep with biventricular heart failure

ObjectivesWe set out to determine the tricuspid valves propensity to (mal)adapt in disease. BackgroundTricuspid regurgitation (TR) is generally considered secondary to right and/or left ventricular disease without organic failure. Interestingly, we and others have previously shown the mitral valve (mal)adapts in functional mitral regurgitation, which may warrant reconsideration of its functional etiology. Whether the tricuspid valve similarly (mal)adapts is mostly unknown. MethodsWe evaluated the (mal)adaptive response of tricuspid valve anterior leaflets (TVALs) from an ovine model in which over-pacing (19 {+/-} 6 days) induced biventricular heart failure and TR (tachycardia-induced cardiomyopathy, TIC, n=33) and compared findings to those from a control group (n=17). In both groups, we performed proteomics, immunohistochemistry, histology, two-photon microscopy, collagen assays, leaflet thickness and morphology measurements, and biaxial mechanical tests. ResultsWe found metabolically active resident valvular cells in TIC TVALs which expressed activation and turnover markers. In TIC TVALs, we observed a 140% increase in collagen content (p=0.016), increased collagen dispersion regionally (p=0.017), a 130% increase in leaflet area (p=0.002), a 140% increase in thickness (p=0.006), and a 130% increase in radial stiffness (p=0.006). ConclusionsOur data suggest that TVALs (mal)adapt during TIC on all scales. This response is likely initiated by activated valvular cells, resulting in collagen turnover, and ultimately leading to thickening, area increase, and stiffening. Our data motivates future studies on the exact pathways leading to tricuspid (mal)adaptation and pharmacological therapeutic strategies for TR. Condensed AbstractIn most cases, tricuspid regurgitation is presumed to originate from valve extrinsic factors. We challenge this paradigm and hypothesize that the tricuspid valve maladapts, rendering the valve at least partially culpable for its dysfunction. As such, we set out to demonstrate that the tricuspid valve, indeed, maladapts in an ovine model of heart disease. In the anterior leaflets, we found alterations on the protein and cell-level, leading to maladaptation in the form of tissue growth, thickening, and stiffening. Our findings may initially motivate mechanistic pathway studies, and in the future, leaflet-targeted pharmacological therapeutic options for tricuspid regurgitation.

bioengineering↗