Cartilage has limited capacity for repair, thus injury often progresses to irreversible cartilage degradation culminating in osteoarthritis and loss of joint function. Osteoarthritis is a major cause of disability and existing therapies often fail to restore healthy articular cartilage, ultimately necessitating total joint replacement. Prevention of osteoarthritis requires diagnostic tools that are capable of detecting changes in cartilage associated with early, potentially reversible cartilage degeneration as well as therapeutic interventions that restore cartilage function and reverse the progression of disease. Toward achieving early detection of degeneration, restoring function, and evaluating regeneration of cartilage, the global objectives of this research were to 1) develop a xenogeneic cartilage graft material with mechanical properties comparable to native cartilage but with reduced antigenicity and 2) investigate relationships between quantitative magnetic resonance imaging (qMRI) and functional properties of cartilage that could inform non-invasive evaluation of cartilage properties in vivo. An approach to antigen removal based on sequential protein solubilization and nucleic acid digestion was developed and optimized in vitro, and then tested in vivo in an animal model. Relationships between qMRI metrics and relevant functional properties of cartilage were examined using self-assembling cartilage as a model.

The results of this work identify several important agents that improve antigen removal from cartilage and further demonstrate the possibility of reducing xenogeneic antigen content while preserving cartilage composition and compressive properties. Further research is needed to achieve immune tolerance in vivo and the results presented here provide future directions for advancing xenogeneic cartilage antigen removal. With regards to detection of early cartilage degeneration and evaluation of cartilage regeneration, several correlations were identified between self-assembling cartilage properties and qMRI metrics, some of which have not been described before in any cartilaginous tissue. Relating these findings to the pathophysiology of cartilage injury and osteoarthritis may help detect changes in cartilage that precede irreversible damage. Finally, the results of this research inform predictions about the quality of selfassembling cartilage in vitro based on non-destructive imaging that could be directly applied to evaluating tissue-engineered cartilage properties in vivo.