CAREER: Understanding the Dynamic Mechanical Adaptations of Bone Tissue at Small Length Scales

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

This Faculty Early Career Development (CAREER) award supports research that will combine mechanics and high-resolution imaging to uncover how human bones adapt under dynamic loads to prevent fracture. During exercise, injury, and repair, bone tissue at nanometer length scales is exposed to constantly changing loads. However, the current framework for understanding fracture is largely based on static and macroscale assessments of bone health. The ability to quantitatively assess and mitigate fracture risk and prescribe treatment requires a fundamental understanding of time-dependent properties of bone tissue at nanometer length scales. This research will work to resolve in real time how the nanoscale constituents of human bones rearrange and deform, when subjected to dynamic loads that mimic physiological conditions ranging from walking to trauma. The project will investigate how this adaptation varies in healthy and osteoporotic human tissue to understand the fundamental causes of increased fracture risk. In the future, it is hoped that this approach will help accelerate assessment of therapies with respect to tissue evolution and fracture. This work integrates educational activities in partnership with local museums and high school educators, to develop interactive modules that teach mechanics and imaging of biological systems to historically underserved and underrepresented high school students. This research program will investigate the adaptation of nanoscale mineralized collagen fibrils in human bone at physiologically relevant, fast time scales. The dynamic and non-affine deformations of bone at the nanoscale will be analyzed to experimentally answer: 1) how the nanostructure of bone changes under cycling loading 2) what mechanisms dictate dynamic fracture in bone and 3) how the components of microscale tissue hierarchy contribute to damage tolerance in healthy and osteoporotic bone. To answer 1) and 2), the program will develop fatigue and dynamic fracture experiments on micron-sized bone samples in scanning electron and synchrotron X-ray microscopes with 30 nm and 20 ms spatio-temporal resolution. The small experimental length scales will uniquely allow the use of small human bone biopsies to answer question 3). In the context of pre-existing macroscale bone mechanics, the research will inform and develop constitutive models to describe strength and toughness with respect to crack velocity in the form of an evolving dynamic cohesive zone. The experimental data will be hosted in an open-source repository and help advance the understanding of how the extracellular matrix adapts at timescales too fast for cells to respond and remodel, with follow-up studies to understand how this impacts cell fate. The approach will establish a generalizable framework for investigating tissue fracture across length and time scales. 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.