Collaborative Research: Investigating the Role of Aging and Type-2 Diabetes Mellitus Collagen Network Impairments on Fracture Behavior Across Physiological and Fall Strain Rates

This award supports a research program to study the biomechanical origins of bone fragility in aging and type-2 diabetic populations. The most basic building blocks of bone are collagen and mineral. Aging and diabetes change the microstructure of bone through increasing the number of interconnections (crosslinks) of bone’s collagen network. This increase in crosslinks is hypothesized to reduce bone’s resistance to fracture. The mechanisms that are responsible for the observed increase in bone fragility will be investigated during the project. The findings are likely to have significant implications for public health, particularly as diabetes prevalence rises. The project supports NSF's mission by promoting scientific progress, advancing national health, and potentially leading to targeted therapeutic treatments that could improve quality of life for all Americans. This work will reveal the role of advanced glycation end product cross-links on fracture behavior at quasi-static and dynamic loading rates representative of physiological and fall-event strain rates. Fracture experiments will be supported by elasto-plastic fracture theory, anisotropic stiffness tensors derived from non-destructive acoustic elastography, and high resolution in-situ imaging to provide new insights of active crack growth mechanisms. Because this study uses human tibia and fibula specimens obtained from healthy and diabetic individuals, we will for the first time be able to assess fracture behavior against bone specific quantities of 15 different advanced glycation end product cross-link types. Statistical analysis will aid in pinpointing the specific mechanisms and advanced glycation end products responsible for bone embrittlement and therefore support targeted therapeutic treatments to recover bone’s fracture resistance. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.