Author's School

School of Engineering & Applied Science

Author's Department/Program

Biomedical Engineering

Language

English (en)

Date of Award

January 2009

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Matthew Silva

Abstract

Woven and lamellar bone formation can be stimulated using mechanical loading. Woven bone forms rapidly in response to damaging loading in a disorganized manner with low mineral density. In contrast, lamellar bone formation can be induced in the absence of damage, and is characterized by its slow, organized deposition and high density. In this dissertation, we first examined the molecular response to woven and lamellar bone formation using damaging and non-damaging dynamic loading protocols, respectively. We observed a significant increase in gene expression related to angiogenesis, cell proliferation and osteogenesis prior to woven bone formation, with significantly lower levels of expression associated with lamellar bone formation. To fully characterize the molecular responses of woven and lamellar bone we used a whole genome microarray. The micorarray results brought to light many inflammatory factors not previously investigated in our model, expanded previous findings about angiogenesis, and strengthened our understanding of the role of osteogenic pathways. Our investigations suggested that angiogenesis is required for successful woven bone formation. We used several angiogenic inhibitors, but were unable to prove the dependence of woven bone formation on angiogenesis. Finally, we sought to separate the effects of static and dynamic strains on bone formation. These findings demonstrate that in the absence dynamic strain, bone damage triggers a woven bone response that leads to a functional repair of whole-bone strength. Overall, the work done in this thesis has enhanced our understanding of bone formation. Future studies will expand on the microarray findings and clarify the role of angiogenesis in woven bone formation.

DOI

https://doi.org/10.7936/K7B85648

Comments

Permanent URL: http://dx.doi.org/10.7936/K7B85648

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