Effect of fluid flow on tissue-engineered cartilage in a novel bioreactor

When damaged through either trauma or disease, articular cartilage exhibits little to no capacity for self-repair, thus prompting surgical intervention to alleviate joint pain. Damaged articular cartilage can degenerate to an arthritic state, leaving the subject with a painful and debilitating condition. Few clinical interventions have proven effective in restoring joint function over the long-term, prompting the exploration of new strategies including tissue engineering. Cells are combined with growth factors in an environment suitable for matrix production and assembly into in vitro derived articular cartilage tissue. Tissue engineering offers the promise of providing an "off-the-shelf" tissue with the matrix composition and mechanical properties similar to that of native tissue which can be implanted into a defect site with the hopes of restoring function. The cells and bioactive factors within the tissue maintain normal tissue homeostasis and grow with the subject, ideally offering a permanent, life-time solution and improved quality of life.;A tissue-engineered articular cartilage construct with the matrix composition and mechanical properties near that of native tissue has yet to be produced. While many strategies to achieve this goal exist, a dominant one is the use of bioreactor systems. Besides being amenable to large-scale bio-processing, bioreactors can provide a mechanical stimulus and/or improve mass transport in order to stimulate tissue development. Mechanical stimuli applied in vitro, such as compression, tension and shear, are inspired by the in vivo setting, as articular cartilage resides in a complex and demanding mechanical environment. Reproducing this environment is hypothesized to condition neo-tissue to become more like native tissue while developing in vitro.;The overall objective of this thesis is to employ a novel flow bioreactor to improve matrix composition and mechanical properties of cartilage constructs for load-bearing applications. Improving the matrix components and mechanical stability of the tissue to be more similar to that of native tissue may improve the ability of the tissue to function in vivo. Our central hypothesis is that exposure of three-dimensional (3D) scaffold-free, tissue-engineered cartilage constructs to physiologically-inspired forces in a novel bioreactor system will enhance cartilage matrix synthesis, leading to more robust mechanical properties. (Abstract shortened by UMI.).