Survival rates following traumatic combat injury have improved due to advances in body armor and battlefield medical care. Specifically, vital organs of the head and torso are better protected; however, the extremities are less protected, and injuries to arms and legs have not significantly decreased. Extremity injuries are most often attributed to explosions, including mortars, rockets, and IEDs (improvised explosive devices). The Wounded Warriors returning with extremity injuries not only have damage to bones and soft tissues, but many also have lost muscle tissue. Currently, the standard of care for extremity damage is coverage of the injury, and not restoration of function of the limb. If significant muscle damage has occurred, however, limb function can be minimal. In this case, functional muscle from a healthy site can be transplanted in an effort to salvage the limb; however, this treatment results in loss of function at the donor site. If muscle loss is significant, amputation of the limb may occur.

Advances in regenerative medicine have demonstrated the potential for restoration of both anatomy and function of tissue following disease and injury. Regenerative medicine thus has potential for limb salvage following combat injuries. Specifically, extracellular matrix (ECM) products have shown to promote functional healing of injured or diseased tissues. Small intestine submucosa (SIS-ECM) is a type of ECM scaffold that is derived from intestinal tissue. The SIS-ECM scaffold preserves the structure and signals of healthy tissue, and as it degrades, it attracts healthy stem cells from neighboring damaged tissue that then regenerate functional site-appropriate tissue. SIS-ECM has been studied extensively both in animal and human studies, and is cleared by the Food and Drug Administration for use in urological, gynecological, gastrointestinal, and soft tissue injuries, as well as in dermal wounds.

Early clinical cases indicate that SIS-ECM also has potential to regenerate functional muscle tissue at injury sites. Other work has aimed at using SIS-ECM to repair the donor site when healthy muscle is transplanted to the injury site. The current study proposes to directly address the restoration of muscle tissue anatomy and function at the injury site with SIS-ECM, thus eliminating the need for additional loss of function at a donor site. Forty (40) subjects with large muscle loss in their upper or lower limbs will be studied. Wounded Warriors or civilian victims of motor vehicle accidents will be the subjects of this clinical study. These populations are included to assess the SIS-ECM technology, both in complex combat injuries and also in the more controlled surgical conditions of civilian reconstructive surgery. SIS-ECM will be grafted directly into injury sites. At 3, 6, 9, and 12 months after treatment the grafted site will be imaged using MRI (magnetic resonance imaging) or X-ray to assess regenerated muscle volume, and biopsies will be obtained to detect stem cells or new muscle tissue. Functional repair of the wounded area will be assessed by strength testing at each time point. Successful completion of this clinical study will provide insight to the use of SIS-ECM as a treatment for anatomical and functional recovery of muscle loss.

An important distinction between this and other studies with ECM in older (over 6 months) muscle defects that have already repaired by scarring is that the proposed study will graft SIS-ECM into wounds less than 3 months old. It is well documented in the field of regenerative medicine that older wounds are not as responsive to treatment as those that are new. Based on the early results in older muscle defects, there is a high likelihood that this aggressive early intervention has the potential to profoundly improve SIS-ECM guided regeneration and have even greater impact than those already observed. The proposed study does not represent a significant increase in risk over the surgical procedures the subjects will already be undergoing for their trauma. The potential benefits for subjects are regeneration of functional muscle with increase in strength, reduction in recovery time, reduction or elimination of disability, and improved appearance and self-esteem. In addition, successfully meeting our aggressive objectives would represent a paradigm shift in the treatment of traumatic tissue injury.