Fiscal Year: 2014
2049 The University of Texas at San Antonio (23609)
Principal Investigator: Wang, Xiaodu
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 273,000
Exceeds $250,000 (Is it flagged?): Yes
Start and End Dates: 8/1/13 <> 7/31/16
Restricted Research: YES
Academic Discipline: MECHANICAL ENGINEERING DEPARTMENT
Department, Center, School, or Institute: Center for Simulation, Visualization and Real Time Prediction (SiViRT)
Title of Contract, Award, or Gift: Nanomechanics of bone fragility
Name of Granting or Contracting Agency/Entity:
National Science Foundation
CFDA Link: NSF
CFDA Linked: Engineering Grants
Objectives: Bone fragility fractures are a major concern for the health care of elderly patients due to its high mortality/morbidity rates and the associated costs. As a natural composite material, ultrastructural changes in bone associated with skeletal disorders (e.g. osteogenesis imperfecta, osteopetrosis/osteomalacia, and osteoporosis) serve as major causes of such fractures. Recent evidence has indicated that the toughness of bone is dependent on three major mechanisms: i.e. damage accumulation (modulus loss), plastic deformation, and viscous energy dissipations. Thus, identifying the underlying origins of these behaviors is not only critical for fully understanding the nanomechanics of bone, but it also provides a mechanistic basis for guiding the development of therapeutic regimens that can specifically target these origins. However, so far such efforts have been significantly restricted due to the lack of effective means to directly scrutinize the in situ behavior of bone at nanoscopic levels. To address this extremely challenging but of high impact issue, we propose in this study a synergistic approach combining synchrotron X-ray scattering and unique mechanical testing techniques to simultaneously examine the mechanical behavior of bone at both nanoscopic and tissue levels. Using this experimental approach, we expect to establish a mechanistic framework to describe the in situ behavior of bone constituents (i.e. mineral crystals and collagen fibrils) and its contribution to the bulk behavior (i.e. modulus loss, plastic deformation, and viscous response) of bone. The eventual goal of this study is to identify the nanoscopic origins of bone fragility. Intellectual Merit: The scientific significance of this study lies in the following aspects: First, the novel approaches developed in this study based on the advanced synchrotron X-ray diffraction techniques will, for the first time, enable us to comprehensively capture the in situ behavior (e.g. strain tensors, residual strain status, damage accumulation, and viscous response) of mineral crystals and collagen fibrils in bone. This will markedly advance our understanding of bone mechanics at nanoscopic levels. Second, since all measurements of the in situ behavior are obtained simultaneously with the bulk behavior of bone, the relationship between nanomechanics and bulk behavior of bone can be readily established under different loading conditions. Finally and most importantly, this study will help identify the ultrastructural origins of bone fragility that dominate the bulk deformation/failure processes of bone. The outcome of this study can be extended to other research areas. For instance, it provides a mechanistic basis for ultrastructural modeling of bone in multiscale simulations. Additionally, identifying the ultrastructural origins of bone fragility fractures may facilitate development of therapeutic regimens that can specifically target these origins. Finally, the methodologies developed could be readily extended in studying ultrastructural changes in bone using small animal models. This will give rise to unique opportunities for studying the interplay between the biology processes and nanomechanics of bone pertaining to different bone disorders. Broader Impacts: As broad educational components of this study, two (2) graduate and two (2) undergraduate students will be recruited and trained each year in this multidisciplinary research program. The underrepresented students will be recruited with high priority for the research program with UTSA being a minority serving institution with more than 50% of its student population being Hispanic and other minority groups,.
In fact, we have been doing so very successfully with the help of the Research Center for Minority Institutions at UTSA. As part of outreach program high school students will also be selected each summer to participate in the hands-on projects related to this study through the High School Students Summer Research Programs at UTSA. In addition, the knowledge obtained from this study will be incorporated into our graduate courses, such as Skeletal Tissue Mechanics and Biomechanics offered by Mechanical Engineering or Biomedical Engineering departments. Moreover, the results of this study will be presented at both national and international conferences, such as NSF Engineering Research and Innovation Conference, ASME Summer Bioengineering Conference, Annual Meeting of Orthopaedic Research Society, Annual Conference of American Society of Biomedical Engineering, and TMS Annual Conference. Finally, the results of this study will be included in a technical book we are planning to write in the area of bone mechanics.