ChE PhD Dissertation Defense: Yang Hu

Name: Yang Hu

Title: Sex-Based Difference in Schwann Cell Migration in Response to Topography, Laminin-derived Peptide and Transforming Growth Factor-β1 as in vitro Models for Peripheral Nerve Repair

Date: 07/17/2025

Time: 12:00:00 PM

Committee Members:
Prof. Rebecca Willits (Advisor)
Prof. Matthew Becker
Prof. Ryan Koppes
Prof. Eno Ebong

Location: 220 Shillman

Abstract:
Peripheral nerve repair highly relies on Schwann cell migration within the nerve gap. Repairing a critical-sized nerve gap (~3-4 cm in humans) remains a significant challenge for satisfactory recover outcomes. Facilitating Schwann cell migration for accelerating nerve regeneration has attracted great research interest. This dissertation explores the individual and synergistic effects of different types of external cues: topography, uniform and gradient of biochemical cues.

First, this dissertation found that female cells moved faster, while male cells were more persistent on glass surfaces, indicating an innate sex-based difference in motility responses. This difference was additionally regulated in both a sex- and diameter-dependent manner by three distinct fiber diameter (0.9, 1.2 and 1.8 µm) provided by Dr. Becker’s lab (Duke University). The smaller fibers attenuated innate motility differences, while they reappeared on the largest fiber.

The second part of this dissertation harnessed the finding that 1.2 µm fibers did not induce migration differences, with YIGSR, a peptide derived from laminin β1 chain, which can facilitate Schwann cell proliferation and directionally guide cell migration. YIGSR-tethered fiber scaffolds in different profiles were characterized and provided (Dr. Becker’s lab) for conducting migration studies. We found that cells responded in both sex- and concentration-dependent manner to uniform concentrations. Directional cell migration only occurred at specific locations along the steepest gradient, indicating a competing effect of contact guidance and tethered YIGSR.

The third part of this dissertation discovered the role of transforming growth factor-β1 (TGF-β1) in defined profiles on Schwann cell migration. We found that uniform TGF-β1 concentrations enhanced Schwann cell migration in a concentration-dependent manner, while no directional migration was observed under TGF-β1 gradients. Understanding how TGF-β1 modulates Schwann cell migration provides insights for developing therapeutic strategies and biomaterials that seek to promote nerve regeneration.