Advisor:
Gilda Barabino, Ph.D. (BME)

Committee:
Edward Botchwey, Ph.D. (BME)
Robert Guldberg, Ph.D. (ME)
Spero Karas, M.D. (Emory University)
Athanassios Sambanis, Ph.D. (ChBE)
Johnna Temenoff, Ph.D. (BME)

Articular Cartilage is a resilient load-bearing soft tissue that covers the ends of bones in synovial joints.  The tissue receives its functional properties from its large, avascular extracellular matrix primarily consisting of collagens, proteoglycans, and water.  The solid phase of the matrix (collagens and proteoglycans) provides the tissue with its strength to resist tensile and shearing loads, while the interaction of the proteoglycans with water in the matrix interstitium gives the tissue its resistance to compressive loads and durability.  The avascular and alymphatic nature of the tissue, however, limit the tissue’s ability to repair itself in the event of an acute traumatic insult.  For example, rupture of the ACL is a common sports injury that often results in collateral damage to the articular surface of the knee joint can result in widespread degeneration characteristic of osteoarthritis.  Tissue engineering has emerged as a promising strategy for the repair partial and full-thickness osteochondral defects.  Unfortunately, the fabrication of large cartilage constructs continues to be plagued by poor nutrient transport to the interior of the tissue resulting in poor tissue growth and necrosis of the embedded cells.  To overcome this constraint, this research aims to develop, characterize, and utilize a microfluidic hydrogel culture system which reduces nutrient transport limitations within engineered constructs by embedding a serpentine microfluidic network within the bulk of the developing tissue.  An integrated theoretical-experimental approach is proposed to investigate issues related to channel spacing, perfusion rate, material selection, and cell sourcing strategies culminating in a continuous, graded phenotype osteochondral tissue graft.