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Preventative Therapeutics for Heterotopic Ossification

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Technical Report,30 Sep 2014,29 Sep 2015

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The Geneva Foundation Tacoma United States

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In this project we study Heterotopic Ossification HO and are a potential novel therapy to cure it. HO consists of formation of extra bone within the muscles, near tendons and ligaments, inside the blood vessels and other places in the body. HO is triggered by trauma, burns, nerve damage, immobilization and other conditions and can also occur in patients undergoing large surgeries such as hip or knee replacement. Because trauma, burns and other severe wounds are regrettably common in our soldiers in the current war theaters and conflicts, HO often affects and afflicts many of them. The consequences of having HO are not minor. Patients with HO can experience loss of normal posture and movement, chronic pain, prosthesis fitting problems, formation of pressure ulcers, deep venous thrombosis and other health problems. Indeed, HO has emerged as the single most important barrier to functional activity and return-to-duty in a recent analysis ofwounded active duty service- members. Subsequent infection remains one of the common and significant complications following blast-related severe fracture and amputation with Acinetobacter Baumannii and Methicillin Resistant Staphylococcus Aureus MRSA being the most common isolate from combat wounds. To more precisely identify the cellular and molecular changes associated trauma-induced HO formation and to test the potential in vivo inhibitor effects of an retinoic acid receptor- agonist called palovarotene, we will use an established rat model of combat-related extremity injuryamputation that incorporates the critical elements commonly associated with combat injury namely blast injury, femur fracture and amputations, soft tissue injury and bioburden.

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