James Landry Lilly

Introduction. Radial nerve palsies are a broad nerve deficit involving pain, weakness, or loss of function in the extensor forearm and posterior hand. These injuries can commonly be associated with humerus shaft fractures, which are most often caused by motor vehicle accidents, gunshot wounds, and falls from a standing position¹. 7-17% of closed humeral shaft fractures result in radial nerve palsies¹. In radial nerve lesions, the distal axon of a neuron is separated from the soma and proximal portion of the axon². When the distal portion of the axon is separated from the rest of the neuron, Schwann cells phagocytose the disintegrating axon over a period of up to one month². Often, the cut nerve requires a scaffold between the 2 ends of the disconnected nerve to guide the biological repair³. The current gold standard of scaffolding is an autograft, but this is not a perfect solution because a second surgery site is required with a limited amount of graft material, and this often results in a sensitivity loss to the patient³. Some nerve conduits are commercially available which have similar efficacy to autografts, but only for short distance repair. For longer distances, the autografts still provide greater results³. However, our understanding of how to promote nerve regeneration within using an artificial nerve conduit is improving. Methods. In order to study the effects of various environments on nerve regeneration, multiple works examined the effects on rats with a transected sciatic nerve, using an autograft as a control. In one study, nerve graft conduits (NGCs) were colonized with fibroblasts, and in another, the NGCs were functionalized with glycosaminoglycans. A third work tested nerve regeneration in NGCs that received varying doses of x-ray irradiation. A final study of NGCs with different material macrostructure and microfiber alignments was assessed. Results. Nerve fibroblast grafting within nerve conduits for regrowth was found to be an effective strategy for promoting regeneration, possibly because of fibroblast release of Neuregulin 1⁴. Glycosaminoglycans were found to influence the adhesion, proliferation, and dedifferentiation of Schwann cells to act as repair cells in nerve regeneration⁵. Low-dose radiation increased nerve regeneration by increasing levels of VEGFA and GAP-43⁶. Lastly, a novel spiral NGC with aligned nanofibers enhanced the rate of nerve regeneration for a 10 mm rat sciatic nerve gap over the course of a 6 week period⁷. Conclusion. The ability of NGCs to improve nerve regeneration in radial nerve palsies is increasing. Aligning the microfibers of the graft can provide topographical cues for the growing axon. Additionally, functionalizing the NGC with both fibroblasts and glycosaminoglycans can increase the Schwann cell recruitment, as well as providing low-dose x-ray irradiation therapy.

1.  Hegeman E. Incidence and Management of Radial Nerve Palsies in Humeral Shaft Fractures: A Systematic Review. Cureus. 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736027/. Accessed April 10, 2022.
2. Gordon T. Peripheral nerve regeneration and muscle reinnervation. International Journal of Molecular Sciences. 2020. https://www.mdpi.com/1422-0067/21/22/8652/htm. Accessed Feb 06, 2022.
3. Hainline B. Peripheral nerve injury in sport: an overview. Handbook of Clinical Neurology. 2018. https://www.sciencedirect.com/science/article/pii/B9780444639547000367?via%3Dihub. Accessed Feb 06, 2022.
4. Fornasari B. Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation. Cells. 2020. https://www.mdpi.com/2073-4409/9/6/1366/htm. Accessed March 23, 2022.
5. Idini M. Glycosaminoglycan functionalization of electrospun scaffolds enhances Schwann cell activity. Acta Biomaterialia. 2019.  https://www.sciencedirect.com/science/article/pii/S1742706119304763?via%3Dihub. Accessed March 23, 2022.
6. Jiang B. X-ray irradiation has positive effects for the recovery of peripheral nerve injury maybe through the vascular smooth muscle contraction signaling pathway. Environmental Toxicology and Pharmacology. 2017. https://www.sciencedirect.com/science/article/pii/S1382668917301990?via%3Dihub. Accessed March 23, 2022.
7. Chang W. Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration. Acta Biomaterialia. 2018. https://www.sciencedirect.com/science/article/pii/S1742706118302496#f0010. Accessed March 2, 2022.