Functional tissue engineering of tendon

描述（由申请人提供）：肌腱受伤后的愈合能力有限。受损的肌腱会引起明显的疼痛和残疾，并最终导致周围关节的不稳定和恶化。肩关节的肌腱（即肩袖）特别容易受伤，在严重的慢性肌腱恶化后，肌腱与骨界面附近经常发生撕裂。目前还没有一种外科修复技术能够完全成功地修复这些损伤。这可能主要是由于手术修复时受损组织的质量较差。将生物可吸收材料与细胞成分相结合的组织工程结构可能最终为这种组织损伤提供解决方案。本研究的目的是确定肌腱成纤维细胞填充的胶原凝胶中组织结构、组成和粘弹性特性之间的关系。有了这些知识，组织工程肌腱当量可以在体外设计，以满足天然组织的功能需求。特别强调将放在重建组织的粘弹性特性，这是必要的适当的功能。本研究的目的是：(1)确定结构（即胶原排列）与粘弹性特性之间的关系，(2)确定成分（即细胞外基质成分）与粘弹性特性之间的关系，以及(3)确定肌腱成纤维细胞填充的胶原凝胶中外部载荷（即静态或循环载荷）与粘弹性特性之间的关系。这种方法将粘弹性性能作为功能目标，并通过改变结构和成分来实现这一目标。为了达到正常肌腱的粘弹性性能，需要结合结构设计和成分设计。

DESCRIPTION (provided by applicant): The ability of tendons to heal after injury is limited. A damaged tendon can cause significant pain and disability, and can ultimately lead to instability and deterioration of the surrounding joint. The tendons of shoulder joint (i.e., the rotator cuff) are particularly susceptible to injury, with tears often occurring near the tendon to bone interface after significant chronic tendon deterioration. No current surgical repair technique has been entirely successful in repairing these injuries. This may largely be due to the poor quality of the injured tissue at the time of surgical repair. A tissue-engineering construct combining a bioresorbable material with a cellular component could ultimately provide a solution for this tissue injury. The goal of this study is to determine the relationships between tissue structure, composition, and viscoelastic properties in tendon fibroblast populated collagen gels. With this knowledge, a tissue-engineered tendon equivalent can be designed in vitro to meet the functional demands of native tissue. Special emphasis will be placed on recreating the viscoelastic properties of the tissue, which are necessary for proper function. The aims of this study are: (1) determine the relationship between structure (i.e., collagen alignment) and viscoelastic properties, (2) determine the relationship between composition (i.e., extracellular matrix components) and viscoelastic properties, and (3) determine the relationship between external loading (i.e., static or cyclic loading) and viscoelastic properties, in tendon fibroblast populated collagen gels. This approach will use viscoelastic properties as the functional goal, and vary the structure and composition to achieve this goal. It is expected that a combination of structural and compositional design will be necessary to achieve the viscoelastic properties of normal tendon.