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Novel Strategies to Combat Post-Traumatic Osteoarthritis (PTOA)


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This program project addresses the overarching clinical need for effective treatments to delay or prevent the development of post-traumatic osteoarthritis (PTOA), a leading cause of disability for military service members and Veterans. The overarching goal is to test the hypothesis that prolonged inflammatory responses to joint injury contribute to progressive cartilage degeneration and subsequent development of PTOA. Consequently, our program project evaluates several innovative strategies to modulate joint inflammation through: [1] cellular and molecular treatments acutely and early after ACL injury in patients and in animal models (Projects 1, 2 and 3), [2] rehabilitation intervention in patients early after ACL reconstruction (ACLR) and prior to OA onset (Project 4), and [3] localized gene therapy for sustained administration of anti-inflammatory therapy in an equine model of PTOA (Project 5). Project 1 will examine the mechanisms by which plasmin and fibrinolysis sustain inflammation and contribute to PTOA. Project 2 will conduct a randomized controlled clinical trial to see whether inhibition of fibrinolysis using tranexamic acid (TXA) acutely after ACL injury reduces inflammation and delays joint degeneration in humans. To address widespread interest in the use of stem cells in the treatment and prevention of OA, Project 3 will evaluate the anti-inflammatory and disease-modifying effects of induced pluripotent stem cell (iPSC)-derived "rejuvenated" human MSC from ACL injured patients. Project 4 will integrate the use of novel quantitative (qMRI) MRI UTE-T2* mapping to evaluate whether an innovative active feedback gait retraining program can reduce both inflammatory and structural markers of elevated OA risk after ACLR. Finally, Project 5 will evaluate the effects of intra-articular anti-inflammatory gene therapy to prevent PTOA. This multidisciplinary program aims to reduce the disease burden of PTOA.



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