Tensile Stimulation of Tissue Engineered Fibrocartilage

描述（由申请人提供）：纤维软骨组织，如 膝关节盘和颞下颌关节盘遍布全身， 经受高压缩力和高拉伸力组合的位置 在正常功能载荷期间横向应变。的 这些组织的显微结构解剖学适当地适应这些 特殊功能需求。富含硫酸软骨素，聚集 蛋白聚糖在经历最高硬度的区域中提供抗压刚度 压缩，而I型胶原原纤维的定向网络使压缩方向对齐。 主拉伸方向的最大拉伸刚度。作为 纤维软骨器官通常具有有限的血管分布， 无血管区域的固有修复能力差， 典型地引发延伸到邻近组织的渐进降解。为 例如，孤立性尿道损伤的患者通常进展为 膝关节软骨在更早的年龄发生骨关节炎性退化 比他们没有受伤的同伴多。最近，组织工程学已经成为一种 修复或替换纤维软骨组织的有前途的替代方案， 从细胞接种的支架生长的生物人造结构。虽然 纤维软骨的结构通常被认为是对特定的 功能需求，很少有人知道适当的范围内的机械 促进结构上有能力的纤维软骨构建体发育所需的力。这项研究是朝着 对纤维软骨中机械力作用的定量理解 组织工程学本研究旨在探讨振荡对 对接种在纤维蛋白凝胶中牛椎间盘纤维软骨细胞（MFC）的张力。 具体而言，它建议：1）量化短期的影响， MFC凝胶上在一定频率和振幅范围内的振荡张力 生物合成和基因表达; 2）量化持续的 振荡张力对细胞外基质积聚和基因表达的影响 3）量化持续振荡张力对MFC凝胶的影响; MFC结构的生物力学性能。这些研究将产生 定量数据描述的影响，振荡拉伸负荷（一个 体内机械环境的重要组成部分）对生物 在工程化纤维软骨中的软骨纤维软骨细胞的行为，和 将有助于机械功能组织工程的发展， 纤维软骨

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.