Access Type

Open Access Thesis

Date of Award

January 2024

Degree Type

Thesis

Degree Name

M.S.

Department

Biomedical Engineering

First Advisor

Harini G. Sundararaghavan

Abstract

Schwann cells 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. Disruptions in normal Schwann cell function such as injury and disease can lead to decreased motor function, sensory capability, and neuropathic pain. Efforts to treat this do not always have consistent or favorable outcomes, so there has been an increased interest in developing tissue engineering solutions to address these problems. Studies have been conducted on various cell types to characterize the cellular response to material properties such as topography and material mechanics, however there appears to be sparse work specifically relating to Schwann cells. This thesis aims to fill this gap by characterizing the Schwann cell response to material topography and material mechanics in both a post-injury model and a disease model, specifically Neurofibromatosis Type 1 (NF1). Hyaluronic acid (HA) was chosen as the base material. HA was methacrylated (MeHA) to alter its mechanical properties through photocrosslinking, and fabricated into gels and aligned electrospun nanofibers to alter its topography. In total, three material conditions were used in this study. Low modified (LMOD) MeHA nanofibers (~30% substitution) and high modified (HMOD) MeHA nanofibers (~60% substitution) were compared for material mechanics. Hydrogels were compared with LMOD MeHA for material topography. Surface and mechanical characterization were conducted on all three material conditions. Nanofibers were found to have a higher Young’s Modulus compared to hydrogels, indicating greater material stiffness, with HMOD MeHA nanofibers having the highest Young’s Modulus. Healthy Schwann cells (WT-SCs) and Plexiform Neurofibroma Schwann cells (NFs) were cultured on all three material conditions, and cell elongation, migration, proliferation, and nerve growth factor (NGF) release were observed. WT-SCs exhibited increased elongation, migration, proliferation, and NGF release on MeHA nanofibers as the material Young’s Modulus increased. In NFs, elongation was greater on MeHA nanofibers, however migration and proliferation increased significantly on hydrogels. NGF release in NFs was the greatest on LMOD MeHA nanofibers. Behaviors observed in WT-SCs are consistent with other studies that observed the cellular response to material mechanics, and suggest that Schwann cells tend to exhibit more pro-regenerative behaviors on aligned fibers with increased material mechanics. In contrast, NF behavior seems to be affected by more material topography compared to material mechanics. The most interesting finding was that NFs appear to elongate slightly more and release significantly more NGF on LMOD MeHA nanofibers despite not exhibiting increases in migration and proliferation. The results of this study offer some interesting characterizations of Schwann cell behavior, which can be utilized for the development of more effective treatments for peripheral nerve injury and NF1.

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