Effect of Fluid Flow on Tissue-Engineered Cartilage in a Novel Bioreactor
Gemmiti, Christopher V.
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Due to its relative avascularity, low cellularity and lack of an undifferentiated cell reservoir, articular cartilage has a limited capacity for self-repair when damaged through trauma or disease. Articular cartilage impairment and the resultant reduced joint function affects millions of people at a substantial cost. In the U.S. alone, over 20 million adults are afflicted with osteoarthritis, costing more than $65 billion per year in health care and lost wages. Surgical techniques have been developed to address small, focal lesions, but more critical sized defects remain without a viable solution. Tissue engineering strategies produce cartilage-like constructs in vitro containing living cells in the hope of replacing damaged cartilage and restoring joint function. However, these constructs lack both sufficient integration into the surrounding tissue following implantation and the mechanical properties capable of withstanding the demanding and complex in vivo loading environment. Our central hypothesis is that exposure of engineered cartilage to fluid-induced shear stress increases the collagen content and mechanical properties (tensile and compressive). The overall objective of this project is to modulate the matrix composition and mechanical properties of engineered cartilage to be more like native tissue using a novel bioreactor. Improving the matrix components and mechanical stability of the tissue to be more similar to that of native tissue may aid in integration into a defect in vivo. The central hypothesis was proven in that shear stress potently altered the matrix composition, gene expression and mechanical properties of both thick and thin engineered cartilage. Modulation was found to be highly dependent on shear stress magnitude, duration, and waveform and affected different matrix constituents and mechanical properties in disparate ways. Our overall objective was satisfied on the basis that the bioreactor created stronger engineered tissues, but with the caveat that the tissues showed an increase in presence of type I collagen. Such an effect would be undesirable for articular cartilage engineered tissues, but could be very beneficial in fibrocartilaginous tissues such as that found in the temporomandibular joint. In conclusion, the novel bioreactor system provides a flexible platform technology for the study of three-dimensional engineered tissues, not just articular cartilage.