A tissue specific approach to enhance tendon repair

描述（由申请人提供）：每年有数百万美国人遭受肌腱损伤，导致工作表现受损和生活质量下降，同时花费数十亿美元的医疗费用。受伤的肌腱愈合不良并形成瘢痕组织，由于其机械强度较差，易于再次损伤。目前的治疗方法在恢复受损肌腱的正常结构和功能方面基本无效。本项目的目的是通过使用新发现的肌腱干细胞（TSCs）、富血小板血浆（PRP）和工程化肌腱基质（ETM）来提高肌腱愈合的质量。将TSC、PRP和ETM植入到建立良好的兔损伤模型的肌腱窗缺损中。然后，分别在短期和长期时间点（6周和26周）评估损伤肌腱的生物学和组织学特性。此外，将通过肌腱样本的力学测试来评估受损肌腱的功能恢复，以确定其结构和力学性能。这项研究具有高度创新性，因为将首次探索肌腱特异性再生细胞（TSC），天然愈合生长因子（PRP）和肌腱特异性基质成分（ETM）的有效组合，以增强肌腱修复。这项研究的发现可能会导致这种联合疗法在临床上的应用，以有效修复或可能再生受伤的肌腱，从而使仅美国就有数百万肌腱损伤患者受益。此外，我们将在这项研究中使用已证实的肌腱损伤模式作为进一步研究其他肌腱类型（包括屈肌腱和肩袖肌腱）愈合问题的“垫脚石”。

DESCRIPTION (provided by applicant): Each year millions of Americans suffer from tendon injuries, resulting in impaired work performance and reduction in quality of life while costing billions of healthcare dollars in treatment. Injured tendons heal poorly and form scar tissue, which is prone to re-injury because of its inferior mechanical strength. Current treatments are largely ineffective in restoring normal structure and function to injured tendons. The objective of this project is to enhance the quality of tendon healing by using newly discovered tendon stem cells (TSCs), platelet-rich plasma (PRP), and engineered tendon matrix (ETM). The TSCs, PRP, and ETM will be implanted into tendon window defects on a well-established rabbit injury model. Then, biological and histological properties of the injured tendon at short and long term time points, 6 and 26 weeks, respectively, will be assessed. In addition, the functional recovery of injured tendons will be evaluated by mechanical testing of tendon specimens to determine their structural and mechanical properties. This study is highly innovative in that a potent combination of tendon-specific regenerative cells (TSCs), natural healing growth factors (PRP), and tendon specific matrix components (ETM) will be explored for the first time to enhance tendon repair. The findings of this study may lead to application of this combination therapy clinically to effectively repair or possibly regenerate injured tendons, thus benefiting millions of tendon injury patients in the United States alone. Moreover, we will use the proven tendon injury mode in this study as a "stepping-stone" for further studying healing problems of other tendon types, including flexor and rotator cuff tendons.