(66f) Engineering Topography to Direct Oligodendrocyte Precursor Cell Fate

Multiple sclerosis is a neurological disease associated with demyelination of neuronal axons and the death of cells that generate the myelin sheath – namely, oligodendrocytes (OLs) and their precursor cells (OPCs). Remyelination of damaged axons is necessary to restore normal neurological function. Studies in two-dimensional (2D) cultures have shown that topographical cues can lead to differentiation of OPCs into mature, myelin-producing OLs. However, three-dimensional (3D) tissue models are necessary to gain further insight into how myelination occurs in vivo, as they are able to replicate geometry and topography better than simple 2D models. Here, we incorporate electrospun polystyrene fibers as axonal mimics into a poly(ethylene glycol) (PEG)-based hydrogel system to study how OPCs respond to topographical cues in a 3D environment. Confocal images show that fibers of approximately 2-4 microns in diameter are distributed along a vertical distance of 200 to 500 micrometers within the gel. Additionally, confocal images show that OPCs exhibit both enhanced process extension more similar to OPCs in vivo and better viability in gels that contain fibers versus typical amorphous PEG-based hydrogels. PCR data and immunostaining will further assess myelin production and gene expression to determine the role of topography on OPC maturation into myelinating OLs. Together, preliminary results suggest that topography is an important factor in guiding the maturation of OPCs into myelin-producing OLs. Furthermore, incorporating topographical cues into amorphous hydrogels can enhance engineered tissue models for the central nervous system to develop better therapeutics and gain insight on diseased or healthy tissue mechanisms.