Chemistry Defense: Yin Mei Chan: "Schwann cell migration and elucidation of sex-based differences using peptide-functionalized aligned fiber scaffolds for peripheral nerve reconstruction"

Schwann cell migration and elucidation of sex-based differences using peptide-functionalized aligned fiber scaffolds for peripheral nerve reconstruction Peripheral nerve repair relies on the ability of Schwann cells to migrate and organize into guiding structures for regenerating axons. To harness this behavior, we have developed aligned fiber scaffolds functionalized with variable concentration gradients of YIGSR, a laminin-derived peptide known to promote Schwann cell motility. Using thiol-ene click chemistries, we generated uniform and gradient patterns of YIGSR on the aligned fibers with spatiotemporal control over tethered peptide concentration during fabrication, yielding two uniform concentration scaffolds of 100 pmol/cm² and 420 pmol/cm² YIGSR, and three gradient profiles of slopes 7 pmol·(cm²·mm)⁻¹, 15 pmol·(cm²·mm)⁻¹, and 30 pmol·(cm²·mm)⁻¹. Schwann cell migration on scaffolds revealed that uniform YIGSR functionalization enhanced migration in a sex-specific and concentration-dependent manner. Female Schwann cells responded with greater motility on 100 pmol/cm² uniform YIGSR-functionalized fibers while male Schwann cell motility was enhanced on both 100 and 420 pmol/cm² compared to non-functionalized fibers. Shallow YIGSR gradients (7 and 15 pmol·(cm²·mm)⁻¹) did not consistently bias Schwann cell directionality in the direction of the gradient. However, 30 pmol·(cm²·mm)⁻¹ gradients induced a haptotactic response, measured by directional velocity and haptotactic index, with both sexes migrating toward regions of higher peptide concentration. Furthermore, we developed mechanically tunable fiber scaffolds that can be orthogonally decorated with both RGD and YIGSR. We show Schwann cell proliferation is enhanced on softer materials. Together, these findings highlight the potential of engineering fiber-based scaffolds with precisely controlled biochemical, topographical, and mechanical cues to direct Schwann cell behavior. Such strategies may ultimately enhance axonal regeneration by guiding neuronal components across segmental nerve defects.