Grants We Funded

Abstract
Satisfactory healing of primary flexor tendon injuries is hampered by an exuberant scar tissue response that forms adhesions between the tendon and synovial sheath. Adhesions impair the gliding function of the tendon and restrict digit range of motion, which in turn can impair the function of the entire hand. Impaired tendon healing represents a significant clinical complication and regaining satisfactory digital function is one of the most pressing challenges facing hand surgeons. We have created a murine model of flexor tendon healing to identify novel molecular targets to decrease adhesion formation and to test the effects of pharmacological inhibition of key mediators of the scar tissue response. Based on our previous work, we have identified Matrix Metalloproteinase 9 (Mmp9) as an important contributor to adhesion formation during flexor tendon healing. Loss of Mmp9 is sufficient to accelerate tissue remodeling and restoration of normal flexor tendon function after injury. We have also demonstrated that expression of Mmp9 only in bone marrow cells is sufficient to cause adhesion formation during healing. Based on these data we are testing the overall hypothesis that expression of Mmp9 in bone marrow mesenchymal stem cells causes increased collagen catabolism which results in subsequent adhesion formation, therefore inhibition of Mmp9 using a pharmacological inhibitor will decrease adhesion formation and improve flexor tendon healing. We will address this hypothesis through the completion of the following two aims: i) Demonstrating enhanced flexor tendon healing and reduced adhesion formation with pharmacological inhibition of Mmp9 activity, ii) Defining the bone marrow cell sub-population that produces Mmp9 and is involved in adhesion formation. Successful completion of these aims will confirm a central role for Mmp9 in adhesion formation and will further enhance our understanding of the cellular and molecular components of adhesion formation. Moreover, this project has the potential to have a profound effect on the clinical outcomes of primary flexor tendon repair procedures. Development of strategies to attenuate adhesion formation without compromising the biomechanical properties of the tendon will decrease complications and accelerate restoration of digit function.

Biography
Alayna E. Loiselle, MD is a Research Assistant Professor in the Center for Musculoskeletal Research and Department of Orthopaedics & Rehabilitation at the University of Rochester Medical Center. Dr. Loiselle obtained her B.S. in Biology from Niagara University in 2004. In 2009 Dr. Loiselle received her Ph.D. in Pathology from the University of Rochester; Her graduate research involved the development of a novel murine model of flexor tendon repair with Dr. Regis O’Keefe. Dr. Loiselle’s Post-doctoral training was completed at the Penn State College of Medicine in Hershey, PA under the direction of Dr. Henry Donahue. Dr. Loiselle joined the faculty at the University of Rochester in 2013. Her laboratory is focused on elucidating the cellular and molecular signals involved in adhesion formation following flexor tendon injuries, with the overall goal of identifying new therapeutic approaches to improve tendon repair outcomes.