PhD Proposal Presentation

Date: Wednesday, May 25, 2016

Time: 10:00 AM

Location: EBB CHOA Seminar Room

Committee Members:

Johnna S. Temenoff, PhD (Advisor)

Edward A. Botchwey, PhD

Robert E. Guldberg, PhD

Claude D. Jarrett, MD

Nick J. Willett, PhD

Controlled Delivery Strategies to Promote the Endogenous Healing of the Supraspinatus Muscle after Severe Rotator Cuff Injury

Severe rotator cuff injury accounts for nearly 50% of major shoulder injuries, and the prevalence continues to increase with age.  Along with substantial pain and poor shoulder function, rotator cuff tears are often accompanied by muscle atrophy and fatty infiltration in the supraspinatus and infraspinatus muscles, even after surgical repair.  Though this muscle degeneration has shown to correlate with higher rotator cuff re-tear rates, current surgical intervention focuses on the tear itself without addressing the surrounding, degenerating muscle tissue.  Thus, the objective of this project is to evaluate the ability for large and small molecule therapeutics, delivered via heparin-based microparticles (MPs), to prevent muscle degeneration by recruiting pro-regenerative cell populations and inhibiting protease-based tissue degradation of the supraspinatus muscle.  Heparin, a highly sulfated glycosaminoglycan (GAG), has been shown by our lab and others to bind positively-charged proteins, and when incorporated within MPs, can enable the controlled release of bioactive proteins over time.  Thus, injectable, hydrolytically-degradable heparin-based MPs will be optimized for the controlled delivery of therapeutics to the supraspinatus muscle after injury.  Subsequently, the effect of these delivered therapeutics will be determined by assessing the level of muscle degeneration up to 6 weeks after full-thickness rotator cuff tear.  Overall, this work aims to elucidate the timeline of muscle degeneration after rotator cuff injury and, through the manipulation of endogenous healing processes, aims to improve the clinical outcomes of patients with severe rotator cuff injury.