Tensile Stimulation of Tissue Engineered Fibrocartilage

描述(申请人提供)：纤维软骨组织，如 膝关节半月板和颞下颌关节盘遍布全身。 经历高压缩和高拉伸组合的位置 在正常功能加载过程中横向应变。这个 这些组织的显微解剖结构适合于这些组织 特殊的功能需求。富含硫酸软骨素，聚集 蛋白多糖在经历最高硬度的区域提供压缩硬度 压缩，而I型胶原纤维的定向网络对齐 主要拉伸方向的最大拉伸刚度。AS 纤维软骨器官通常有有限的血管，损伤孤立 对无血管区域具有较差的固有修复能力 通常会引发累及邻近组织的渐进性降解。为 例如，单纯性半月板损伤的患者通常进展为 膝关节软骨退行性变的早期骨性关节炎 而不是他们未受伤的同龄人。最近，组织工程学已经成为一种 修复或替代纤维软骨组织的有希望的替代方法 从细胞种植的支架中生长出来的生物人造结构。尽管 纤维软骨的结构通常被认为是对特定的 功能需求，对机械的适当范围知之甚少 促进具有结构能力的纤维软骨结构的发展所需的力量。这项研究是迈向以下目标的重要第一步 定量认识机械力在纤维软骨中的作用 组织工程学。这项研究建议探索振荡的影响 种植在纤维蛋白凝胶中的牛半月板纤维软骨细胞(MFC)的张力。 具体地说，它建议：1)量化短期的影响 MFC凝胶在一定频率和幅度范围内的振荡张力 生物合成和基因表达；2)量化持续的影响 振荡张力对细胞外基质积聚和基因表达的影响 MFC凝胶；3)量化持续振荡张力对 MFC构建物的生物力学特性。这些研究将产生 描述振荡拉伸载荷(AN)影响的定量数据 体内机械环境的重要组成部分)对生物 半月板纤维软骨细胞在工程化纤维软骨中的行为 将为机械功能组织工程的发展做出贡献 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.