There are an estimated 11,000 patients who suffer spinal cord injury (SCI) each year in the United States and approximately 200,000 chronic SCI patients. In addition, for US warfighters deployed abroad, SCI has become a common consequence of exposure to blast from improvised explosive devices (IEDs).

Injury to the sensitive spinal cord occurs due to crush or compression of the backbones (vertebrae), such as from falls and automobile crashes, or from penetrating trauma, such as bullet wounds or shrapnel from IEDs. These injuries damage important nerve fibers called "axons" that transmit signals to and from the body and brain through the spinal cord. This axon damage can lead to partial or complete paralysis, depending upon the area of the cord at which the injury occurs. In these extreme cases, repair and recovery are often non-existent, and the patient is left to live life confined to a wheelchair.

A major challenge to repairing an injured spinal cord is to coax remaining axons to grow across the wound site and reconnect on the other side. However, spinal cord wounds are commonly several centimeters in length, and there are many chemical signals in the spinal cord that actually inhibit the growth of axons.

Here, we propose to apply a completely new strategy to create living "jumper cables" that can bridge even extensive spinal cord wounds. This approach capitalizes on a recent discovery in our laboratory that axon bundles can be "stretch-grown" in culture. By applying mechanical tension to the axons in culture, we are able to create axon bundles of up to one million axons reaching several centimeters in length. We can remove these engineered axon bundles out of the culture by embedding them in a gelatin. This "construct" of gelatin and axon bundles has recently been transplanted into injured spinal cords of rats -- matched to the length of a 1-centimeter wound. We found that the construct survived for at least 1 month after transplantation and that transplanted axons grew out into the rats' spinal cords. This demonstrates the potential for the transplanted construct to promote the formation of a "relay" of electric signals across the spinal cord wound.

With this proof of concept, we now propose to evaluate potential recovery of limb function and the formation of relays in transplanted rats with SCI -- evaluating animals over 6 months. If successful, this therapy will have a substantial impact on the field of SCI treatment and recovery by demonstrating that even large devastating spinal cord wounds can be repaired.