A tissue specific approach to enhance tendon repair

增强肌腱修复的组织特异性方法

• 批准号: 8486402
• 负责人: JAMES H-C. WANG
• 金额: $ 19.43万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486402
• 关键词: American; Animals; Area; Autologous; Biological; Biomechanics; Blood; Blood Platelets; Bone Marrow; Bone callus; Calculi; Cells; Cicatrix; Clinical Treatment; Coagulation Process; Collagen; Combined Modality Therapy; Data; Defect; EGF gene; Engineering; Family; Fibroblast Growth Factor 2; Flexor; Generations; Growth Factor; Healed; Healthcare; Housing; Human; Implant; In Situ; In Vitro; Inferior; Injury; Insulin-Like Growth Factor I; Lead; Ligaments; Maintenance; Mechanics; Medicine; Mesenchymal Stem Cells; Metabolic; Modeling; Mus; Natural regeneration; Orthopedics; Oryctolagus cuniculus; Osteogenesis; Patients; Performance at work; Phenotype; Plasma; Platelet-Derived Growth Factor; Proliferating; Property; Quality of life; Rattus; Recovery of Function; Rotator Cuff; Source; Specimen; Stem cells; Structure; Tendon Injuries; Tendon structure; Testing; Time; Tissue Engineering; Tissues; United States; Vascular Endothelial Growth Factors; achilles tendon; clinical application; cost; healing; implantation; improved; in vivo; injured; innovation; ligament injury; progenitor; regenerative; repaired; restoration; self-renewal; stem cell differentiation; treatment effect

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.

描述（由申请人提供）：每年数以百万计的美国人遭受肌腱损伤，导致工作表现受损和生活质量的降低，同时造成数十亿美元的医疗保健费用。受伤的肌腱愈合不佳并形成疤痕组织，由于其较低的机械强度，这很容易受伤。目前的治疗在恢复受伤肌腱的正常结构和功能方面基本上是无效的。该项目的目的是通过使用新发现的肌腱干细胞（TSC），富含血小板的血浆（PRP）和工程性肌腱矩阵（ETM）来提高肌腱愈合的质量。 TSC，PRP和ETM将植入良好的兔损伤模型上的肌腱窗口缺陷。然后，将评估损伤肌腱在短期和长期时间点分别为6周和26周的生物学和组织学特性。此外，将通过机械测试肌腱样品来评估受伤肌腱的功能恢复，以确定其结构和机械性能。这项研究具有很高的创新性，因为将首次探索肌腱特异性再生细胞（TSC），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，以增强肌腱修复。这项研究的结果可能导致该联合疗法在临床上应用有效修复或可能再生受伤的肌腱，因此仅在美国就可以使数百万肌腱损伤患者受益。此外，我们将在这项研究中使用验证的肌腱损伤模式作为“垫脚石”，以进一步研究其他肌腱类型的愈合问题，包括屈肌和肩袖肌腱。