Mechanical Stimulation for TMJ Disc Tissue Engineering

纤维软骨组织，如颞下颌关节盘，在正常功能负荷时，在经历一个方向的高压迫和横向的高张力的组合时，可以在全身各处发现。这些组织的微观结构解剖是适当地适应这些特殊的功能需求。富含硫酸软骨素的聚集蛋白多糖在经历最高压缩的区域提供压缩刚度，而I型胶原原纤维的定向网络将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，并且孤立于无血管区域的损伤具有较差的内在修复能力，并且通常会引发渐进式退化并扩展到邻近组织。例如，颞下颌关节椎间盘穿孔或孤立性半月板损伤的患者通常比未受伤的患者更早发展为相关关节软骨的骨关节炎退化。最近，组织工程已经成为一种有前途的替代修复或替换纤维软骨组织的生物人工结构，这种结构是由细胞种子支架生长而成的。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，但人们对促进纤维软骨结构发育所需的机械力的适当范围知之甚少。这项研究代表了对纤维软骨组织工程中机械力的定量理解的重要的第一步。本研究旨在探讨振荡压缩和张力对纤维蛋白凝胶中植入的牛半月板纤维软骨细胞（mfc）和关节软骨细胞（BACs）的影响。具体而言，该研究建议：1)量化在一定频率范围内的短时间振荡压缩和张力对MFC-和bac -种子凝胶的生物合成和基因表达的影响；2)量化持续振荡压缩和张力对MFC-和bac -种子凝胶细胞外基质积累和基因表达的影响。这些研究将产生描述振荡机械刺激对工程纤维软骨生物行为影响的定量数据，并将有助于机械功能组织工程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.