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

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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.