A tissue specific approach to enhance tendon repair

描述(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，生活质量下降，同时花费数十亿美元的医疗费用。损伤的肌腱愈合不良，形成疤痕组织，机械强度较低，容易再次损伤。目前的治疗方法在恢复损伤肌腱的正常结构和功能方面很大程度上无效。该项目的目标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。在已建立的兔损伤模型上，TSCs、PRP和ETM将被植入肌腱窗缺损处。然后，将评估损伤肌腱在短期和长期时间点的生物学和组织学特性，分别为6周和26周。此外，还将通过对肌腱标本进行力学测试来评估受伤肌腱的功能恢复情况，以确定其结构和力学性能。这项研究具有很高的创新性，首次探索了肌腱特异性再生细胞(TSCs)、自然愈合生长因子(PRP)和肌腱特异性基质成分(ETM)的有效组合，以促进肌腱修复。这项研究的发现可能导致将这种联合疗法应用于临床，以有效修复或可能再生受损的肌腱，从而使仅在美国就有数百万肌腱损伤患者受益。此外，我们将使用本研究中已证实的肌腱损伤模型作为进一步研究其他肌腱类型的愈合问题的垫脚石，包括屈肌和肩袖肌腱。

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.