Leah E. Anderson

BME PhD Defense Presentation

Date: 2023-08-24
Time: 10:00 AM
Location / Meeting Link: In Person Location: Suddath Seminar Room; Zoom Link: https://gatech.zoom.us/j/91293226393

Committee Members:
Advisor: Johnna Temenoff, PhD Committee Members: Nick Willett, PhD; Edward Botchwey, PhD; Young Jang, PhD; Jarrod Call, PhD;


Title: Spatio-temporal controlled delivery strategies for the prevention of muscle degeneration after severe rotator cuff tear

Abstract:
Rotator cuff tear is a significant musculoskeletal injury. Following rotator cuff tendon injury, the corresponding muscle undergoes degenerative changes due to unloading and disuse. The standard of care after severe rotator cuff tear is tendon reattachment, but even after reattachment and associated rehabilitation protocols, the muscle degeneration that occurs after injury is not fully reversed. Furthermore, the degree of muscle degeneration before repair has been shown to correlate to poor surgical outcomes. Thus, there is a need for treatment strategies to reduce or prevent muscle degeneration after severe rotator cuff tear. The long-term goal of this research was to employ treatment and biomaterial delivery strategies that influence the muscle cellular milieu in a spatio-temporal manner, to prevent muscle degeneration after severe rotator cuff tear or repair. In Aim 1, using an acute rotator cuff injury model (no tendon repair), systemic delivery of a bone marrow mobilizing agent, VPC01091, was used to “push” cells into circulation, while the chemokine SDF-1alpha, was locally delivered to injured rat supraspinatus muscle via hydrolytically degradable N-desulfated heparin-based microparticles to “pull” cells to the injury site and increase cell recruitment over previously observed cellular changes due to SDF-1alpha treatment alone. In Aim 2, hydrolytically degradable N-desulfated heparin-based hydrogel fragments were utilized for the spatialized delivery of SDF-1alpha, and thus cellular recruitment, to two distinct regions of rat supraspinatus muscle after rotator cuff tear. Finally, in Aim 3, supraspinatus muscle healing response after tendon repair was explored with and without micronized dehydrated human amnion/chorion membrane (dHACM) treatment in a clinically relevant model of delayed tendon reattachment in rat.