Effect of Material Properties on Neurofibromatosis Type 1 Schwann Cell Behavior

Schwann cells (SC) are the principal glia in the peripheral nervous system, supporting normal peripheral nerve function, particularly in the myelination of motor and sensory axons of the peripheral nerves. In Neurofibromatosis Type 1 (NF1), disruptions in normal SC function can lead to decreased motor function, sensory capability, and neuropathic pain. There is no cure for NF1 and any available treatments are for symptom management such as surgical removal and drug therapies that do not always have consistent or favorable outcomes. As a result, there has been an increased interest in understanding SC behavior in NF1. This study focuses on characterizing SC response to material topography and material mechanics in an NF1 model. Based on previous studies conducted on other aberrant cells, we hypothesized that material topography, rather than mechanics alone, would have a significant impact on key behaviors such as elongation, migration, proliferation, and nerve growth factor release (NGF). We also investigated the effect of mechanics by using methacrylated hyaluronic Acid (MeHA) in this study to alter its mechanical properties through photocrosslinking (2.5-33.6 kPa). MeHA was fabricated into gels and aligned electrospun nanofibers to alter its topography. Plexiform neurofibroma Schwann cells (pNF-SCs) were cultured and cell elongation, migration, proliferation, and nerve growth factor (NGF) release were observed. Elongation was greater on nanofibers; however, migration and proliferation increased significantly on hydrogels. NGF release was the greatest on 30% substitution nanofibers. The results of this study offer further characterization of pNF-SC behavior, which can be utilized for the development of a more refined in vitro model of NF1.