Nonetheless, post yield failure in MGO treated tendons was characterized by appearance of distinct subpopulations of unloaded fibrils among mechanically loaded fibrils. This indicates that some fibrils fractured at a location somewhere along their length with the remaining length of these fibrils remaining in an intact quarter-staggered arrangement. Given that the D-period length of the fractured fibril subpopulation did not relax completely back to an unloaded state, they apparently remain slightly stretched, probably due to lateral connections to adjacent fibrils that were still under load. This parallels observations from mechanical tests within diabetic rat tissues, in which distinct failure behavior in these tissues has been demonstrated to be a consequence of increased lateral interconnectivity across multiple collagen fibrils that simultaneously fail. This is in contrast to failure behavior of native samples, where signal intensities decreased after yielding without any peak splitting, indicating either a GW786034 thinning of the sample or more likely the loss of quarter-staggered organization. A third key finding is that MGO treatment reduces inherent collagen fibril viscoelasticity. Our previous work has shown that MGO treatment inhibits tendon stress relaxation, which is thought to be mainly governed by collagen fiber shear and sliding. The results from the present study indicate that a reduced fibril viscoelasticity may also be a substantial factor in the loss of viscous response at the fiber level and the related shear matrix. However, it remains unclear how nano-scale effects of AGE could translate to mechanical effects across these different orders of magnitude in scale. An eventual involvement of AGE altered fibril surface charges can in principle change the viscoelastic mechanical properties of soft tissue. Comparing our observation of AGE mediated loss of fibril viscoelasticity to others, Svensson and colleagues found no mechanical differences in single fibrils from diabetic rats and that the investigated biochemical markers of AGE remained equal to controls. Considering what is known from the biomaterials field regarding chemical cross-linking of collagen constructs, Yang and colleagues have described distinct effects on single collagen fibril viscoelasticity using cross-linking reagents of different crosslinking length. With the “zero length” cross-linker EDC -carbodiimide) there was no change of fibril modulus found aside from an increased failure behavior and a reduced viscoelasticity, which echoes the results of the present study. In contrast, glutaraldehyde formed cross-links have a length of least 1.3 nm length that can bridge across micro-fibrils, and glutaraldehyde treatment has been shown to increase fibril modulus. Based on these observation we hypothesize that the lack of an increased fibril modulus in MGO cross-linked tendon is due to its shorter cross-linking length in the range from 0.26 nm to 0.70 nm.