Date of Award

12-2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

Committee Chair

Russell Main

Committee Member 1

Eric Nauman

Committee Member 2

Matthew Allen

Committee Member 3

Sarah Calve

Committee Member 4

Joseph Wallace

Abstract

Dynamic mechanical loading plays an important role in regulating bone geometry and strength. A healthy skeleton adapts to the bone tissue strain profile and magnitude of loads it experiences on a daily basis in order to maintain reasonable safety factors. In skeletal diseases, such as osteoporosis, a bone’s ability to adapt and maintain structural integrity in response to increased mechanical strains is apparently impaired, which allows skeletal resorption to progress unabated and could eventually lead to mechanical failure. In order to develop better treatments for bone wasting diseases, it is important to understand the mechanobiology of how the healthy skeleton responds to mechanical load. The non-invasive, axial compressive murine tibial loading model has been used extensively to study skeletal adaptation, but sole use of rodent models propagates a large gap in understanding skeletal sensitivity and response to load across terrestrial vertebrate groups. The avian skeleton exhibits several features that make it unique compared to the mammalian rodent skeleton, and these differences could affect how the avian skeleton responds to mechanical load relative to the rodent skeleton. To begin expanding our understanding of skeletal sensitivity across vertebrate species, we developed a novel non-invasive avian tibiotarsal (TBT) loading model using the chukar partridge to complement the use of the murine tibial loading model. For both the mouse and the bird, relatively similar increases in strain stimuli via experimentally applied loads were determined through a combination of in vivo strain gauging and finite element models. The cross-sectional strain distributions during locomotion and experimental loading were further characterized in the bird TBT after validating the use of planar strain theory for cortical bone loaded in bending. In response to several weeks of experimentally applied loading, the mouse tibia adapted its geometry and mass. In contrast, the birds adapted their cross-sectional geometry without complementary increases in bone mass while suppressing normal endocortical bone growth. Lastly, in order to study cortical bone’s response to mechanical load without the potentially confounding effects of varied systemic factors across species, we developed a novel isolated cortical bone culture model that can be mechanically loaded in vitro. We validated that osteocytes in a murine tibial bone segment maintained adequate survival over a five day culture period, and comprehensively characterized the load induced strain profile. Overall, this work takes novel steps to develop and validate comparative in vivo and in vitro models for comparatively assessing skeletal sensitivity across terrestrial vertebrate species. Continued work in this direction will enhance our understanding of how a healthy skeleton is regulated to maintain adequate bone strength.

Download

Share

COinS