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Title page for ETD etd-03202017-104333


Type of Document Master's Thesis
Author Kavanaugh, Taylor Elizabeth
URN etd-03202017-104333
Title Antioxidant microspheres as drug delivery vehicles for the prevention of post-traumatic osteoarthritis
Degree Master of Science
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Craig Duvall, Ph.D. Committee Chair
Todd Giorgio Committee Member
Keywords
  • Osteoarthritis
  • Drug Delivery
  • Reactive Oxygen Species
  • Microspheres
  • Post-traumatic Osteoarthritis
Date of Defense 2017-01-13
Availability restricted
Abstract
Osteoarthritis (OA) is a disease characterized by degradation of joints with the development of painful inflammation in the surrounding tissues. Post-traumatic osteoarthritis (PTOA) is OA that develops following a traumatic injury to the joint. Currently, there are a limited number of treatments for this disease and many of these only provide temporary, palliative relief. Here, we discuss polymer drug delivery systems that can provide targeted and sustained delivery of imaging and therapeutic agents to OA-affected sites. Polymer based microparticles were investigated as a therapeutic for PTOA. The inherent antioxidant function of poly(propylene sulfide) (PPS) microspheres (MS) was dissected for different reactive oxygen species (ROS), and therapeutic benefits of PPS-MS were explored in mechanically induced PTOA. PPS-MS scavenged hydrogen peroxide (H2O2), hypochlorite, and peroxynitrite but not superoxide in vitro in cell-free and cell based assays. Elevated ROS levels were confirmed in a mouse model of PTOA. In the PTOA model, PPS-MS reduced matrix metalloproteinase activity. These results suggest that local delivery of PPS-MS to site of PTOA reduces articular cartilage destruction. These results motivate further exploration of PPS as a stand-alone, locally-sustained antioxidant therapy and as a material for microsphere-based, sustained local drug delivery to inflamed tissues at risk of ROS damage.
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