Mechanical Stimulation for TMJ Disc Tissue Engineering

纤维软骨组织，如颞下颌关节盘，在正常的功能负荷下，可以在身体各处经历单向高压缩和横向高张力的组合。这些组织的显微解剖结构适当地适应了这些特殊的功能需求。富含硫酸软骨素的聚集性蛋白多糖在受压缩程度最高的区域提供压缩硬度，而I型胶原纤维的定向网络使最大的拉伸硬度与主要拉伸方向保持一致。纤维软骨器官通常血管有限，孤立于无血管区域的损伤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。例如，TMJ间盘穿孔或单纯性半月板损伤的患者通常在比他们的非损伤队列更早的年龄进展为相关关节软骨的骨关节炎退化。最近，组织工程学已经成为一种很有前途的替代方案，可以用细胞种子支架生长的生物人工结构来修复或取代纤维软骨组织。尽管纤维软骨的结构通常被认为是对特定功能需求的适应，但人们对促进具有结构能力的纤维软骨结构的发展所需的适当范围的机械力知之甚少。这项研究代表了量化理解机械力在纤维软骨组织工程中的作用的重要的第一步。本研究旨在探讨振荡压缩和拉伸对种植在纤维蛋白凝胶中的牛半月板纤维软骨细胞(MFC)和关节软骨细胞(BAC)的影响。具体地说，它建议：1)量化在一定频率范围内的短期振荡压缩和拉伸对MFC和BAC种子凝胶中生物合成和基因表达的影响；以及2)量化持续振荡压缩和拉伸对MFC和BAC种子凝胶中细胞外基质积累和基因表达的影响。这些研究将提供描述机械振荡刺激对工程化纤维软骨生物学行为影响的定量数据，并将有助于开发具有机械功能的组织工程化纤维软骨替代物。

Fibrocartilaginous tissues such as the temporomandibular joint disc are found throughout the body in locations experiencing combinations of high compression in one direction and high tension 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. Fibrocartilaginous organs generally have limited vascularity, and 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 perforated TMJ discs or isolated meniscal injuries typically progress to osteoarthritic degradation of the associated 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 bioartificial 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 compression and tension on bovine meniscal fibrochondrocytes (MFCs) and articular chondrocytes (BACs) seeded in fibrin gels. Specifically, it proposes to: 1) Quantify the effects of short-duration oscillatory compression and tension over a range of frequencies on biosynthesis and gene expression in MFC- and BAC-seeded gels; and 2) Quantify the effects of sustained oscillatory compression and tension on extracellular matrix accumulation and gene expression in MFC- and BAC-seeded gels. These studies will produce quantitative data describing the influence of oscillatory mechanical stimuli on the biological behavior of engineered fibrocartilage, and will contribute to the development of mechanically functional tissue engineered fibrocartilage replacements.