Thermal alteration of collagenous tissue subjected to biaxial isometric constraints

Clinical thermal therapies are widespread and gaining in appeal due to improved technology of heating devices and promising results. Outcomes of thermal treatment are often unpredictable and suboptimal, however, due in part to a lack of appreciation of the underlying biothermomechanics. There is a pressing need, therefore, to understand better the role of clinically-controllable parameters on the thermal damage processes of tissue. Heretofore, researchers have primarily sought to understand this process through various uniaxial experiments on tissues containing collagen as their primary constituent. Most biological tissues experience multiaxial loading, however, with complex boundary constraints inclusive of both isotonic and isometric conditions. The primary focus of this work is on the isothermal denaturation of fibrillar collagen subjected to a biaxial isometric constraint. Results from our tests reveal a complicated process, the kinetics of which are not easily measured. Evolving isometric contraction forces during heating do not correlate with resultant mechanical behaviors, as thermal shrinkage does in biaxial isotonic tests. Furthermore, resultant mechanical behaviors at variousdurations of heating reveal a two phase process with a rate dependent on the amount of isometric stretch. For tissues heated at 75oC for 15 minutes, at which point the first phase of mechanical alteration dominates for all constraints herein, resultant mechanical behaviors correlate well with the amount of isometric stretch. The correlation is similar to that between isotonic loads and resultant mechanical behaviors from previous studies. In light of the need for a better measure of thermal damage in isometric tests, we performed a histological analysis of tissues heated under varying constraints. Results show a good correlation between the level of isometric constraint and thermally-induced histological aberrations. Finally, we demonstrate that our seemingly limited and qualitative knowledge can be applied well to a specific clinical application: namely, the use of glycerol as a clearing agent for laser therapies. Our results suggest that glycerol is safe to use for such therapies because it increases the thermal stability of fibrillar collagen, and its hyperosmotic effects on mechanical behavior are fully reversed upon rehydration