Peripheral nerve injuries present a serious clinical challenge with greater than 250,000 peripheral nerve trauma cases being reported every year in the United States. After nerve trauma, the standard clinical operating procedure is to oppose the two nerve ends and suture them together without generating tension where possible. While autografts are the best clinical bridging option available today, there are many drawbacks to this procedure, including the need for a secondary surgery, loss of donor site function, limited availability, and neuroma formation at the donor or graft site. Therefore there is a clear and urgent, unmet clinical need to find an alternative approach to the use of autografts. Despite our best efforts, finding alternative 'nerve bridges' for peripheral nerve repair remains challenging - of the four FDA approved nerve 'tubes' for use in the clinic, none is typically used to bridge gaps longer than 10 mm due to poor outcomes. Here, we propose an innovative hypothesis - we hypothesize that recruiting anti- inflammatory regenerative monocytes preferentially to the nerve gap will bias the regenerative cascade to help bridge long nerve gaps without the need for long-term exogenous trophic factor delivery. Specifically we will evaluate the efficacy of acutely delivering fractalkine to investigate its ability to attract regenerative monocytes, and subsequently influence nerve bridging across long nerve gaps.
Traumatic nerve injuries resulting from motor vehicle accidents, gunshot wounds, fractures and other forms of penetrating trauma affected more than 250,000 US patients in 2002. Current clinical approaches such as using autograft are not completely successful in cases of long gaps, but also have additional complications because of involvement of secondary surgery. We propose a novel approach of using body's own mechanisms involving immune cells and topographical cues to achieve successful clinical outcomes matching or exceeding currently available options.
| Lyon, Johnathan G; Mokarram, Nassir; Saxena, Tarun et al. (2017) Engineering challenges for brain tumor immunotherapy. Adv Drug Deliv Rev 114:19-32 |
| Mokarram, Nassir; Dymanus, Kyle; Srinivasan, Akhil et al. (2017) Immunoengineering nerve repair. Proc Natl Acad Sci U S A 114:E5077-E5084 |
