SUBJECT: Ph.D. Dissertation Defense
BY: Eric Vanderploeg
TIME: Tuesday, May 9, 2006, 10:30 a.m.
PLACE: IBB Building, 1316
TITLE: Mechanotransduction in Engineered Cartilaginous Tissues: in vitro Oscillatory Tensile Loading
COMMITTEE: Dr. Marc E. Levenston, Chair (ME)
Dr. Andres J. Garcia (ME)
Dr. Michelle C. LaPlaca (BME)
Dr. Robert M. Nerem (ME)
Dr. Harish Radhakrishna (BIO)


Disease of articular cartilage and fibrocartilage tissues severely compromises the quality of life for millions of people. Although current surgical repair techniques can address symptoms, they do not adequately treat degenerative joint diseases such as osteoarthritis. Thus, novel tissue engineering strategies may be necessary to combat disease progression and repair or replace damaged tissue. Cartilaginous tissues are subjected to a complex mechanical environment consisting of compressive, shear, and tensile forces. Therefore, engineered replacement tissues must be mechanically and biologically competent to function after implantation. The goal of this work was to investigate the effects of oscillatory tensile loading on engineered cartilaginous tissues elucidating important aspects of chondrocyte and fibrochondrocyte mechanobiology. To investigate the metabolic responses of articular chondrocytes and meniscal fibrochondrocytes, various oscillatory tensile loading protocols were used to identify stimulatory parameters. Longer durations of continuously applied loading were inhibitory, whereas short durations and intermittently applied loading could stimulate matrix production. Subpopulations of chondrocytes, separated based on their zonal origin within the tissue, were also found to differentially respond to tensile loading. Finally, up to 14 days of intermittently applied oscillatory tensile loading induced modest increases in construct mechanical properties, but longer durations adversely affected these mechanical properties and increased degradative enzyme activity. These results provide insights into cartilage and fibrocartilage mechanobiology by elucidating cellular responses to tensile mechanical stimulation. Understanding the role that mechanical stimuli can play in the generation of engineered cartilaginous tissues will further the goal of developing successful treatment strategies for degenerative joint diseases.