Ph.D. Proposal by Torri Rinker
Ph.D. Proposal Presentation
Time: Wednesday, October 8, 10:00 AM
Location: Bunger Henry Building, 311, Georgia Tech
Adviser: Johnna Temenoff, Ph.D. BME/Georgia Tech
Todd McDevitt, Ph.D. BME/Georgia Tech
Tom Barker, Ph.D. BME/Georgia Tech
Hang Lu, Ph.D. ChBE/Georgia Tech
Luke Brewster, M.D., Ph.D. Department of Surgery/Emory University
Title: "Controlling Spatial and Temporal Presentation of Heparin to Modulate Cellular Differentiation"
Heparan sulfate and heparin are a glycosaminoglycans (GAGs) known to have a strong affinity for proteins and are involved in a variety of cellular processes, including tissue development and cellular differentiation. Specifically, heparan sulfate is known to bind growth factors involved in chondrogenesis and has the potential to modulate soluble factors within the chondrocytic microenvironment toward the goal of developing improved cellular therapies for cartilage tissue repair. Due to the innate ability of heparan sulfate and heparin to modulate growth factor presentation, heparin may have the unexplored potential to act as the sole bioactive component in therapeutic systems. Thus, the objective of this proposal is to evaluate the ability of heparin microparticles (MPs) and cell coatings to modulate chondrogenic differentiation by spatially and temporally manipulating growth factor presentation. We will meet this objective by evaluating the ability of heparin MPs and cell coatings to modulate differentiation in ATDC5 cell spheroids, an in vitro model of chondrogenesis. Furthermore, we will design core-shell heparin-poly(ethylene glycol) (PEG) MPs to achieve temporal control over heparin presentation within ATDC5 spheroids. Finally, MSC-chondrocyte co-culture, known to promote MSC chondrogenesis through cellular communication, will be used to understand how heparin can influence differentiation by modulating diffusion of signaling molecules between two cell types. Overall, this research will provide deeper insight into the influence of spatially and temporally controlled heparin presentation on cellular differentiation and soluble factor diffusion.