Request for Funding
Medical Student Research Fellowship for Summer 2011

All descriptions must contain enough detail to permit an assessment of the problem that is to be addressed and the methodologies that are to be employed. Please be careful to outline the role that the student will play in the project that is described. Please ensure that all relevant approval numbers (IRB, IACUC) are provided.

Mentor:            Christopher Chen, Ph.D.       
Department:                Orthopaedic Surgery
Room number:            H7.102
Mail Code:                   8870
Phone number:           214-648-2276
E-mail:             Chris.Chen@UTSouthwestern.edu

Project title:                 Role of load in cartilage degradation after trauma Injury

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IACUC approved project number (where applicable): N/A

Project Type: Basic research

Brief Description of Project:

Joint load is a stimulating factor for normal cartilage metabolism, but can be harmful to the sensitive cells and matrix in injured cartilage.  Continuous passive motion used in clinical setting has been shown to improve surgical outcomes, but its underlying mechanism and relationship to pro-inflammatory events is not completely understood. A better understanding of the mechanobiology of injured cartilage and the effects of cyclic loads on tissue degradation is an important step for optimizing the treatments for cartilage degeneration. The experiments in this study are designed to test the hypothesis that cartilage degradation following overload injury is modulated by daily cyclic load and correlated with the level of pro-inflammatory cytokines.  The specific aim of this study is to determine the effects of cyclic daily loads (0.5MPa) versus immobilization (0 MPa) on matrix degradation (PG/collagen loss), cell death (cell vital staining) and pro-inflammatory cytokines (IL-1 and TNF-a) of articular cartilage following trauma injury.

Project title:     Role of BMP-7 in the development of Post-traumatic Osteoarthritis

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IACUC approved project number (where applicable): APN2009-0272

Project Type: Animal-based research

Brief Description of Project:

Posttraumatic osteoarthritis (PTOA) is the degeneration of articular cartilage in response to an injurious event.  An in vivo animal model utilizing a pendulum device to deliver a single impact load to rabbit medial femoral condyles less than their fracture threshold has previously demonstrated significant chondrocyte apoptosis following impaction. Recently, we described that a single high-energy impact load causes PTOA in rabbits via a decrease in chondrocyte metabolism.  Our null hypothesis is that intraarticular supplementation of BMP-7 in this model will not significantly decrease the amount of chondrocyte apoptosis or posttraumatic osteoarthritis.  The specific aim of this study: To determine the effect of BMP-7 on chondrocyte apoptosis following an impact load of articular cartilage.  Following a single impact load, we will use osmotic pumps, implanted subcutaneously, to deliver continuous BMP-7 to the knee joint surface.  Comparing the extent of chondrocyte apoptosis between sham and experimental groups will be accomplished using light microscopy, fluorescence microscopy, and immunochemical techniques.

Previous Research Activities or Publications with Medical Students:

Dr. Chen has been working with more than ten medical students in the past several years from Brown University, Cornell University, Duke University, and George Town University, Penn State University and Linköping University in Sweden.  Research topics are closely related to orthopedic surgery and arthritis. It has been a fruitful and successful experience, which yields 5 peer-reviewed publications and several are in preparation and in review.

Levin A.S., Chen C.T., Torzilli P.A. (2005) Cell death in cyclically loaded cartilage: Effects of tissue maturation. In press, Osteoarthritis and Cartilage 2005 Jun;13(6):488-96.
Ranawat A.S., Vidal A.F., Chen C.T., Zelken J., Turner A.S., and Williams R.J. (2008) The material properties of fresh cold-stored allografts used for the reconstruction of osteochondral defects after one year in vivo. Clinical Orthopaedics and Related Research 466(8):1826-36.
Gulotta L., Rudzki J.R., Kovacevic D., Milentijevic D Williams R. Chen C.T. (2009) Chondrocyte Death and Cartilage Degradation Following Autologous Osteochondral Transplantation Surgery in a Rabbit Model.  Am J Sports Med 2009; 37(7):1324-33