title: Two-dimensional stress-relaxation behavior of human skin as influenced by non-enzymatic glycation and the inhibitory agent aminoguanidine.
abstract: 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 glycated human skin samples. Since skin is subjected to biaxial tension, we used two-dimensional multiaxial testing which better reflects the in vivo situation than the uniaxial testing mode. For native skin samples from the abdominal region we found a direction-dependent elastic stress strain behavior. The 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 generated in a direction-dependent mode. A marked increase of the direction-dependent stiffness was found upon long-term incubation with glucose-6-phosphate. 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-dimensional relaxation tests at consecutive radial strains were inversely correlated with non-enzymatic modification. Only at 30% radial strain a significant decrease of the viscous fraction engendered by glucose-6-phosphate was 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 aminoguanidine, a potential therapeutic agent for patients with diabetes mellitus. Our findings suggest that additional cross-links generated by long-term glycation cause two-dimensional biomechanical alterations in human skin, which can be unequivocally detected by multiaxial testing.
authors.affiliation: Ludwig Boltzmann Institut für experimentelle plastische Chirurgie, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Reihsner
authors.forename: E J
authors.initials: EJ
authors.lastname: Menzel
mesh_terms: D000368:Aged; D001696:Biomechanical Phenomena; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology*; D004548:Elasticity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019298:Glucose-6-Phosphate / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008433:Mathematics; D008875:Middle Aged; D012212:Rheology; D012879:Skin Physiological Phenomena / Q000187:drug effects; D013314:Stress, Mechanical; D014783:Viscosity
chemical_list: D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D019298:Glucose-6-Phosphate; C004479:pimagedine