UC San Diego

Peripheral nerve injuries (PNIs) are injuries to the peripheral nervous system, typically caused by a traumatic event, and are very common in a combat and trauma setting. The nerve autograft has been regarded as the “golden standard” for PNIs, where a piece of nerve tissue, sourced from an autogenous sensory nerve, is transplanted to the site of injury. However, the nerve autograft has many shortcomings, such as pain and loss of function at the donor nerve site, neuroma formation, and risk of infection following surgery. Our lab developed a novel multichannel scaffold approach (MCS), which uses linear microstructures to restrict axonal regeneration to one direction. The MCS approach was then further strengthened by the addition of brain-derived neurotrophic factor (BDNF), which have been shown to help increase the rate of axon regeneration, and thus potentially eliminate the need for a donor nerve. In this study, the MCS approach was tested in vivo by injuring the sciatic nerve of rats and then implanting the following therapies: open tube, nerve autograft, multichannel scaffold, and the multichannel scaffold with the addition of BDNF. 12 weeks post implant we found that rats implanted with MCS, or MCS/BDNF, or nerve autograft had similar number of regenerating axons. This was significantly higher than the number of regenerating axons observed in open tube control subjects (no channels). Our findings also showed that the MCS approach, both with and without BDNF, was successful in orienting regenerating axons into the proper pathway from proximal to distal aspect of the injury compared to nerve graft and open tube implants where axons were seen deviating from this path. Our experiment was able to demonstrate that the MCS with and without BDNF therapy performs significantly better in terms of axonal regeneration and axon alignment than the open tube therapy in the sciatic nerve rat model. Thus, a multichannel scaffold can be a replacement for the standard of care, which is the nerve autograft, preventing the serious side effects of this procedure and providing an off-the-shelf alternative. The development of the MCS approach allows researchers to apply similar approaches to peripheral nerve injuries throughout the body, such as cranial nerve injuries where donor grafts are needed.