Calorimetric study of extracellular tissue matrix degradation and instability after gamma irradiation

Native extracellular tissue matrix (ECM) is increasingly used for tissue repair and regeneration. The kinetics of gamma irradiation damage on human dermis ECM was studied by differential scanning calorimetry (DSC). Dermis ECM was irradiated at a low-dose rate of 0.23 kGy h(-1) in order to study the progression of ECM damage as the gamma dose increased from 0 to 32 kGy. The study showed that the effect of gamma irradiation above 2 kGy was predominantly peptide chain scission. As the gamma dose increased, the stability of irradiated ECM decreased further, and multiple ECM domains of different stability were detected. Even a moderate gamma dose (7-12 kGy) could decrease the onset denaturation temperature of ECM to below body temperature. DSC analysis also showed partial and spontaneous protein denaturation in gamma-irradiated, rehydrated ECM at 37 degrees C. In vitro rehydration tests confirmed that a significant fraction of the irradiated ECM disintegrated into minute ECM fragments at 37 degrees C, although the irradiated ECM appeared to be normal at 4 degrees C and room temperature. DSC data were correlated well to effects of gamma irradiation on ECM microstructure, mechanical property and in vitro cell response reported earlier by us. A model was presented to describe the kinetics of gamma-irradiation-induced alterations of tissue ECM properties.