Abstract

Chemical crosslinks in collagens resulting from binding of advanced glycation end-products, have long been presumed to alter the stiffness and permeability of glycated tissues. Recently, we developed a stochastic mechanical model for the response and failure of uniaxially deformed sciatic nerve tissue from diabetic and control rats. Here, we use our model to determine the likely correlation of fibril glycation with failure response, by quantifying statistical differences in their response. Our four-parameter model describes both the non-linear toe region and non-linear failure region of these tissues; the four parameters consist of (1) collagen fibril alignment, (2) fiber bundle waviness, (3) Weibull shape parameter for fibrillar strength, and (4) modulus-normalized Weibull scale parameter for fibrillar strength. Using an equal load sharing model we find that diabetic and control tissues had shape parameters of 9.88 ± 5.50 and 4.33 ± 3.67 ( p = 0.043), respectively, and scale parameters of 0.28 ± 0.07 and 0.58 ± 0.25 ( p = 0.033), respectively, implying that the diabetic tissue behaves in a more brittle manner, consistent with more highly crosslinked fibrils. We conclude that biochemical crosslinking directly affects measured mechanical properties. Further, this mechanical characterization may prove useful in mapping alterations in stiffness and permeability observed in glycated tissues.

Full Text
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