| The overall objective of this project is to evaluate chondrocytes and bone marrow mesenchymal stem cells exposed to proinflammatory cytokines and Triamcinolone Acetonide (Kenalog) under physiologic oxygen conditions with development of a 3D in vitro cell-based drug model using polycaprolactone scaffolds. Osteoarthritis is the most common form of arthritis affecting nearly 27 million Americans or 12.1% of the adult population of the United States. It constitutes a major disease and disability worldwide, being the fifth largest contributor to disability life years. It is estimated that osteoarthritis will cost the U.S. economy nearly ;To simulate the in vivo microenvironment, cells were subjected to 6% O2 and 21% O2 levels and their growth, function and morphology were evaluated. To date there is no cure for osteoarthritis thus pharmacologic focus has been on pain relief. There are numerous medications that have been used clinically to relieve pain. Intra-articular corticosteroids have been used clinically for over 50 years with good outcomes associated with pain relief. Yet, there is controversy within the literature on the effects of intra-articular corticosteroids on chondrocytes. Recent advances in biology and material sciences have brought tissue engineering to the forefront of cartilage repair techniques. With development of various 3D in vitro constructs, there have been promising strides toward engineering functional cartilage tissue. Polycaprolactone (PCL) scaffolds have been successfully shown to foster a healthy environment for growth of cells as well as cartilage tissue.;The final section of this project looks to develop a 3D cell-based drug model using PCL scaffolds that can be used for more efficient and cost-effective preclinical screening of potential anti-osteoarthritic treating drugs. The overall goal of this thesis is to gain a deeper understanding of how chondrocytes and bone marrow mesenchymal stem cells function after exposure to inflammatory conditions and to evaluate their response to corticosteroids as well as to develop a 3D in vitro cell-based testing method for a more informed prediction of drug candidate efficacy and safety. |
