PhD Proposal by Julia Andraca Harrer
Julia Andraca Harrer
BME PhD Proposal Presentation
Time: 3:00PM - 5:00PM
Location / Meeting Link: https://uoregon.zoom.us/j/97287235553
Nick J. Willett, Ph.D. (Advisor); Scott Hollister, Ph.D.; Jay Patel, Ph.D.; Johnna Temenoff, Ph.D.; Joel Boerckel, Ph.D.
Title: Mechanical Regulation of Bone Regeneration following Critical Bone Loss Injury
Critically sized bone defects due to traumatic injury do not heal without intervention and result in longterm functional deficits. Native bone physiology is strongly influenced by mechanical loading, which also plays an important role in bone regeneration throughout the healing process. Rehabilitation post-injury provides a mechanical stimulus during the healing process; however, clinical rehabilitation regimens are typically conservative with long periods of non-loading, often leading to impaired tissue regeneration, atrophy, and fibrosis. The overall objective of this thesis is to elucidate the effects of an osteogenic small molecule therapeutic and mechanical loading on mechanosensitive signaling pathways during bone regeneration following an injury resulting in critical bone loss. The overarching hypothesis is that coupling early initiation of mechanical loading via exercise with osteogenic treatment will enhance bone regeneration through mechanoresponsive signaling in osteoprogenitor cells and improve functional use of the injured limb. To address this hypothesis, the following Specific Aims are proposed: (1) engineer a therapeutic strategy for bone regeneration combining rehabilitation and an osteogenic small molecule targeting the BMP pathway and (2) establish the impact of rehabilitation regimens on molecular mechanisms of mechanotransduction during early stages of bone regeneration. Upon completion, this thesis will provide significant insight into the mechanosensitive mechanisms regulating bone regeneration and functional recovery after critical injury