The increased skeletal propensity to fracture is a major concern in health care of elderly populations due to the deteriorated bone quality. Cellular and/or molecular changes in bone due to aging or diseases are most likely reflected in the ultrastructure and material properties of bone constituents (i.e., mineral and collagen phases), which would eventually affect the post-yield behavior (microdamage formation) and the quality of the tissue. As a major measure of bone quality, the toughness of bone is mainly determined by the post-yield behavior of the tissue. Previous studies have demonstrated that the post-yield deformation of bone is most likely realized through the formation of two types of microdamages: microcrack and diffuse damage. Thus, elucidating the generating mechanisms of these microdamages and its relationship with bone constituents would significantly facilitate the understanding of age and disease related bone fractures. Although the ultrastructural and material properties of bone constituents is most likely related to the microdamage formation in bone, the underlying mechanism is poorly understood. To address this issue, the present study proposes a novel probabilistic damage model of mineral-collagen composites that can be used to study the mechanism of the tensile post-yield behavior (i.e., nano/microdamage formation) for bone tissues, and further to assess the contribution of ultrastructural and material properties of the bone constituents to the process. The hypothesis of this study is that microdamage formation (microcrack or diffuse damage) in bone is dependent on the ultrastructural and material properties of collagen fibrils and mineral matrix in the tissue.
Two specific aims will be addressed as follows:
Aim1 : To develop a probabilistic failure model of mineral-collagen fibril composite to predict the mechanisms of damage formation in bone (i.e., either microcrack or diffuse damage) as a function of ultrastructural and material properties of mineral and collagen constituents: To do so, micromechanics combined with the probabilistic damage mechanics approaches will be used to develop a probabilistic damage model of mineral-collagen fibril composites. Using this novel model, patterns of microdamage progression as a function of ultrastructural and material properties of bone constituents will be examined.
Aim 2 : To verify the probabilistic failure model using bone samples from several mice models: Several mice models (i.e., C57BL/6, C3HE/H, and oim mice) with varied properties of the mineral and collagen phases will be utilized to test the effects of ultrastructural and material properties of the mineral and collagen phases on the post-yield behavior of bone (i.e., microdamage formation). These experimental data will be compared with the predictions by the mechanistic model developed in Aim 1. This study will, for the first time, provide a novel probabilistic damage mechanics approach to examine the effect of ultrastructural and material properties of bone constituents on the post-yield behavior of bone. Moreover, this model will provide significant insights into the underlying mechanism of age and disease related bone fractures. Elucidating these fundamental issues is not only scientifically important, but also give rise to the future development of strategies in prediction and prevention of age-related and osteoporotic bone fractures. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG027780-02
Application #
7282716
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Williams, John
Project Start
2006-09-15
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2009-08-31
Support Year
2
Fiscal Year
2007
Total Cost
$141,974
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
800189185
City
San Antonio
State
TX
Country
United States
Zip Code
78249
Dong, X Neil; Zoghi, Mahyar; Ran, Qitao et al. (2010) Collagen mutation causes changes of the microdamage morphology in bone of an OI mouse model. Bone 47:1071-5
Dong, X Neil; Guda, Teja; Millwater, Harry R et al. (2009) Probabilistic failure analysis of bone using a finite element model of mineral-collagen composites. J Biomech 42:202-9