Mechanical Stimulation for TMJ Disc Tissue Engineering

纤维软骨组织，如颞下颌关节盘，在整个身体的位置，在正常的功能负荷过程中经历一个方向上的高压缩和横向方向上的高张力的组合。这些组织的显微结构解剖学适当地适应这些特定的功能需求。富含硫酸软骨素的聚集蛋白聚糖在经历最高压缩的区域中提供压缩刚度，而I型胶原原纤维的定向网络使最大拉伸刚度与主要拉伸方向对齐。纤维软骨器官通常具有有限的血管分布，并且孤立于无血管区域的损伤具有较差的内在修复能力，并且通常引发延伸至邻近组织的进行性降解。例如，患有TMJ盘穿孔或孤立性颞下颌关节损伤的患者通常在比他们的未受伤队列早得多的年龄进展到相关关节软骨的骨关节炎退化。最近，组织工程已经成为一个有前途的替代修复或替代纤维软骨组织与生物人工结构生长的细胞种子支架。虽然纤维软骨的结构通常被认为是适应特定的功能需求，很少有人知道的适当范围的机械力，以促进发展的结构主管纤维软骨结构。这项研究是一个重要的第一步，定量了解机械力在纤维软骨组织工程中的作用。本研究旨在探讨振荡压缩和拉伸对种植于纤维蛋白凝胶中的牛桡骨纤维软骨细胞（MFC）和关节软骨细胞（BAC）的影响。具体而言，它建议：1）量化在一定频率范围内的短持续时间振荡压缩和张力对MFC和BAC接种的凝胶中的生物合成和基因表达的影响;和2）量化持续振荡压缩和张力对MFC和BAC接种的凝胶中的细胞外基质积累和基因表达的影响。这些研究将产生定量的数据，描述振动机械刺激对工程化纤维软骨的生物学行为的影响，并将有助于机械功能的组织工程化纤维软骨替代物的发展。

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.