BONE AND SOFT TISSUE RESEARCH.

Source: The Combat Casualty Care Research Program website, www.usacc.org.

Rationale for Investment
Data from ongoing conflicts is consistent with previous conflicts, showing extremity injuries are common and have significant morbidity. Returning wounded soldiers to duty depends on treating these wounds such that functional tissues are regenerated. Until recently the bone and soft tissue research program has focused on providing improved devices for the treatment of combat wounds such as individual issue tourniquets and improved irrigation devices and fluids. Having delivered on this device centered approach, we are currently focused on reducing the morbidity associated with traumatic injury to the extremities by leveraging the rapidly advancing field of regenerative medicine. Severe injuries to the extremities following explosions leave many Soldiers unable to return to duty and their training and expertise are lost. A subset in this group are returned to duty but with greatly reduced mobility, stamina and agility resulting from the partial or complete loss of limbs. A significant number of these individuals are in highly skilled MOS’s that cost many hundreds of thousands of dollars to train. The ability to return them to high function would save millions of dollars and would also improve their quality of life and increase morale.

Overarching Objective:
In collaboration with industry and academic partners, translate the promise of regenerative medicine to improved functional outcomes in injured soldiers. Improved function will improve both the quality of life for individual soldiers and the rate of return to duty after injury.

The program includes:

Establishment of a university-based center of excellence in tissue repair and regeneration to develop materials and processes that facilitate the regeneration of tissues after traumatic injury.
Investigation of strategies to replace damaged or missing tissues in the extremities to include bone, muscle and
Investigation of treatments to prevent and treat wound infections
Investigations of the pathophysiology of injury and methods for limiting the severity of injury through early intervention

Development Strategy:
Research efforts will focus on improving capabilities to repair penetrating extremity injury, to return Soldiers to duty, and to improve their quality of life. Biomedical research and pre-clinical trials will be performed to establish safety and effectiveness of treatments to re-grow blood vessels, nerves, muscle, bone and skin in casualties suffering from blast and projectile damage. Novel delivery systems and broad spectrum antibiotics developed by the biomedical community will be assessed for far forward use in preventing and treating wound infection.

This regenerative approach will be focused in 4 major thrust areas:

Segmental defects in long bones –

Guide the civilian tech base into militarily relevant research.
Leverage civilian efforts by performing key experiments to apply civilian research and products into military-relevant questions.

Direct Muscle Trauma – Intramural research program will:

Inform the civilian research community about the need for treatments that promote maximal return of function in skeletal muscle after injury
Focus on translating civilian treatment research (Extra-cellular matrix, mesenchymal stem cell therapy, growth factors) into military-relevant solutions
Perform key experiments to test emerging therapeutics in relevant animal models.

Burn and extremity wound healing and infection – Despite adherence to wound care protocols, and rapid evacuation, extremity wound contamination and infection remains a significant problem with evacuated burns constituting 5% of all evacuated combat casualties.
Intramural research will:

Test potential therapeutics in military-relevant models and contexts
Inform industry and academia of the military need
Continue to collaborate with the USAISR burn center to transition therapeutics

Heterotopic Ossification – There is emerging concern that was identified as a result of ongoing communication with Army orthopedists indicating that the incidence in combat casualties appears to far exceed that in civilian trauma. It appears that there is minimal active research outside the Army, and what research exists may be of limited value (e.g., radiation therapy as a pre-treatment). Because of the growing knowledge of basic mechanisms of mesenchymal stem cell differentiation, significant leverage may exist for addressing this issue.

Future Direction:
Transition solutions aimed at regenerating large wounds in the extremities and disfiguring wounds to the head and face to the clinic in five years but limit the number of tissue types to one or two (Potential tissue types to study are: bone, muscle, blood vessels, cartilage, and nerves).

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