Tensile Stimulation of Tissue Engineered Fibrocartilage

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DESCRIPTION (provided by applicant): Fibrocartilaginous tissues such as the knee menisci and temporomandibular joint disc are found throughout the body in locations experiencing combinations of high compressive forces and high tensile strains in a transverse direction during normal functional loading. The microstructural anatomies of these tissues are appropriately adapted to these particular functional demands. Chondroitin sulfate-rich, aggregating proteoglycans provide compressive stiffness in regions experiencing the highest compression, while an oriented network of type I Collagen fibrils aligns the greatest tensile stiffness with the primary tensile direction. As fibrocartilaginous organs generally have limited vascularity, injuries isolated to the avascular regions have a poor intrinsic capacity for repair and typically initiate progressive degradation extending to adjacent tissues. For example, patients with isolated meniscal injuries typically progress to osteoarthritic degradation of knee articular cartilage at a much earlier age than their non-injured cohort. Recently, tissue engineering has emerged as a promising alternative to repairing or replacing fibrocartilaginous tissues with bioartifical constructs grown from cell-seeded scaffolds. Although the structure of fibrocartilage is generally viewed as an adaptation to specific functional demands, little is known about the appropriate ranges of mechanical forces required to promote development of structurally competent fibrocartilage constructs. This study represents an important first step towards a quantitative understanding of the role of mechanical forces in fibrocartilage tissue engineering. This study proposes to explore the influence of oscillatory tension on bovine meniscal fibrochondrocytes (MFCs) seeded in fibrin gels. Specifically, it proposes to: 1) Quantify the effects of short-duration oscillatory tension over a range of frequencies and amplitudes on MFC gel biosynthesis and gene expression; 2) Quantify the effects of sustained oscillatory tension on extracellular matrix accumulation and gene expression in MFC gels; 3) Quantify the effects of sustained oscillatory tension on the biomechanical properties of MFC constructs. These studies will produce quantitative data describing the influence of oscillatory tensile loading (an important component of the in vivo mechanical environment) on the biological behavior of meniscal fibrochondrocytes in an engineered fibrocartilage, and will contribute to the development of mechanically functional tissue engineered fibrocartilage.