Julia Andraca Harrer
BME PhD Defense Presentation
Date: 2024-09-26
Time: 12:00 PM - 1:00 PM Eastern Standard Time
Location / Meeting Link: https://gatech.zoom.us/j/98957019111
Committee Members:
Nick Willett, PhD (Advisor) Johnna Temenoff, PhD Jay Patel, PhD Scott Hollister, PhD Joel Boerckel, PhD
Title: Regenerative Engineering and Rehabilitation Strategies for Bone Regeneration and Functional Restoration
Abstract:
Critical bone defect injuries present a significant clinical burden. The current standard of care often results in nonunion and requires multiple revisions surgeries. Even if rescue attempts are eventually successful, the long healing period ultimately leaves patients with long-term disability and chronic pain. Bone healing relies on a precise interplay of biochemical and mechanical cues to guide the healing process. However, the current biological treatments have many limitations and negative side effects, and current bone stabilization methods prevent any mechanical stimulation within the defect region. The overarching hypothesis of this thesis is that an osteogenic therapeutic will enhance bone formation and bridging while the early induction of mechanical stimulation via rehabilitation will enhance bone formation and promote the functional recovery of the injured limb. Therefore, the overall objective of this thesis is to establish a multi-faceted approach to treat critical bone loss injuries. This approach integrates an osteogenic therapeutic to stimulate bone regeneration with a rehabilitation regimen beginning early in the healing process to target functional restoration. This will be achieved through four specific aims: 1) engineering an osteogenic small molecule therapeutic targeting the BMP pathway to induce bone regeneration, 2) establishing the impacts of early induction of mechanical loading on bone healing, 3) developing a mouse bone defect model to determine the impacts of early induction of mechanical loading on functional recovery, and 4) establishing a combined therapeutic strategy consisting of an osteogenic therapeutic to induce bone formation and early rehabilitation to enhance functional recovery. Overall, this thesis uncovers novel osteogenic therapeutics, and furthers our understanding on the effects of mechanical stimulation through rehabilitation regimens on bone healing and functional restoration. The knowledge attained by this thesis provides the groundwork for the development of integrative therapeutic strategies that target functionality alongside tissue regeneration.