Graft harvest as a model of tendon injury; Trajectory of recovery and clinical outcomes

项目总结/摘要 我的职业目标是弥合肌腱基础科学和临床研究之间的差距，以优化肌腱的治疗 损伤，使用个性化的负荷和恢复处方。为了实现这一目标并填补我的经验空白，我 设计了一项发展计划，将提供临床试验和大型试验管理方面的培训和指导 多中心研究，应用和解释混合效应模型，以及对组织生物学的理解。研究 活动将提供免费的经验和试点数据，以建立自己作为一个独立的临床医生，科学家。 理由：健康的肌腱功能对维持生活质量至关重要。过度使用的肌腱损伤在 社会，发生率超过髋关节和膝关节骨关节炎的总和。这些伤害影响了结构和 肌腱的机械性能，这降低了肌腱功能，下肢性能，参与日常活动 活动，最终是生活质量。肌腱损伤的治疗旨在促进肌腱重塑， 恢复结构、机械性能和肌腱功能的目标。然而，疼痛是使用的主要措施 以评估临床环境中的治疗效果，这是肌腱重塑的不良指标。因此，临床医生 使用干预措施，而没有能力确定应用是否适当，增加了剩余风险 损伤和损伤复发。研究和临床之间的这种差距是由于对肌腱的理解不足 人体组织变化及其临床意义。肌腱结构和力学性能的变化先于 症状的发展，使得难以捕获这些特性的损伤前值。无损伤前 值，不可能确定由于伤害而导致的变化程度，预期的恢复轨迹，或 这些变化与临床结果的关系。肌腱移植物切取部位可能为研究肌腱提供一种新的模型 伤害，提供了机会，捕捉收获前的措施，结构和机械性能。 具体目的：（1）确定移植物收获后移植部位结构的变化。(2)识别移植部位的变化 移植物收获后的机械性能。(3)确定移植部位结构变化与 机械性能与移植物收获后的临床结局。 方法：这将是一项辅助性、单中心、前瞻性队列研究，受试者为稳定性2试验的参与者， 匹兹堡大学，旨在确定前交叉韧带失败高风险患者的最佳移植物选择 韧带重建（ACLR）。将在术前以及术后6周、3个月、6个月、12个月和24个月完成评价 采用髌骨或股四头肌肌腱移植物进行ACLR，以评估移植部位结构和力学性能的变化， 股四头肌肌肉表现、肌腱疼痛和下肢功能。这些措施将与 稳定性2试验的现有结果，以获得参与者临床状态的完整信息。 临床影响：研究结果将提高我们对肌腱愈合的理解，为测试干预措施提供新的模型， 并加速采用合适的肌腱损伤结局措施。从长远来看，这可能会防止残留 肌腱功能受损，恢复参与日常活动和生活质量。

PROJECT SUMMARY/ABSTRACT My career goal is to bridge the gap between tendon basic science and clinical research to optimize treatment of tendon injuries, using individualized load and recovery prescription. To achieve this goal and fill gaps in my experience, I have designed a development plan which will provide training and mentorship in administration of clinical trials and large multicenter studies, applying and interpreting mixed-effects models, and understanding of tissue biology. The research activities will provide complimentary experience and pilot data to establish myself as an independent clinician-scientist. Rationale: Healthy tendon function is critical to preserving quality of life. Overuse tendon injuries are rampant across society, occurring at a rate exceeding hip and knee osteoarthritis combined. These injuries impact the structural and mechanical properties of the tendon, which reduces tendon function, lower extremity performance, participation in daily activities, and ultimately, quality of life. Treatments for tendon injuries are designed to promote tendon remodeling, with the goal of restoring structure, mechanical properties, and tendon function. However, pain is the primary measure used to assess treatment effectiveness in clinical settings, which is a poor measure of tendon remodeling. Thus, clinicians are using interventions without the ability to determine whether the application is appropriate, increasing the risk of residual impairments and injury recurrence. This gap between research and the clinic is due to a poor understanding of tendon tissue changes in humans and their clinical implications. Changes in tendon structure and mechanical properties precedes the development of symptoms, making it difficult to capture pre-injury values of these properties. Without pre-injury values, it has not been possible to determine the degree of change due to injury, the expected trajectory of recovery, or how these changes relate to clinical outcomes. The tendon graft harvest site may provide a new model for studying tendon injuries, providing the opportunity to capture pre-harvest measures of structural and mechanical properties. Specific Aims: (1) To identify changes in graft site structure after graft harvest. (2) To identify changes in graft site mechanical properties after graft harvest. (3) To determine the association between changes in graft site structural and mechanical properties with clinical outcomes after graft harvest. Methods: This will be an ancillary, single-site, prospective cohort study of participants in the STABILITY 2 Trial at the University of Pittsburgh, which aims to identify optimal graft choice in patients at high risk of failed anterior cruciate ligament reconstruction (ACLR). Evaluations will be completed pre-surgery, and 6 weeks, 3-, 6-, 12- and 24-months after ACLR with a patellar or quadriceps tendon graft to evaluate changes in graft site structural and mechanical properties, quadriceps muscle performance, tendon pain, and lower extremity function. These measures will be combined with existing outcomes from the STABILITY 2 Trial to obtain a complete picture of participants’ clinical status. Clinical Impact: Findings will improve our understanding of tendon healing, provide a new model for testing interventions, and accelerate the adoption of suitable outcome measures for tendon injury. Long-term, this may prevent residual impairments in tendon function and restore participation in daily activities and quality of life.