Two-dimensional stress-relaxation behavior of human skin as influenced by non-enzymatic glycation and the inhibitory agent aminoguanidine

In order to simulate the in vivo stress alterations of diabetic skin in an in vitro model, we examined the viscoelastic properties of long-term glycat ed human skin samples. Since skin is subjected to biaxial tension, we used two-dimensional multiaxial testing which better reflects the in vivo situat ion than the uniaxial testing mode. For native skin samples from the abdomi nal region we found a direction-dependent elastic stress-strain behavior. T he viscous stress component was separated from the elastic stress component by relaxation tests at consecutive incremental steps of radial strains. We hypothesize that glycation-induced changes in the tissue stiffness are gen erated in a direction-dependent mode. A marked increase of the direction-de pendent stiffness was found upon long-term incubation with glucose-6-phosph ate. This increase was statistically significant for the maximum principal elastic stress component which was highly correlated with the degree of non -enzymatic collagen modification. The viscous fractions obtained from two-d imensional relaxation tests at consecutive radial strains were inversely co rrelated with non-enzymatic modification. Only at 30% radial strain a signi ficant decrease of the viscous fraction engendered by glucose-6-phosphate w as observed together with a direction-dependent significant increase of the expectation value of the time constant. The biomechanical and biochemical effects of long-term glycation could be partially reversed by aminoguanidin e, a potential therapeutic agent for patients with diabetes mellitus. Our f indings suggest that additional cross-links generated by long-term glycatio n cause two-dimensional biomechanical alterations in human skin, which can be unequivocally detected by multiaxial testing. (C) 1998 Elsevier Science Ltd. All rights reserved.